Metastatic Breast Cancer

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.

Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.

These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.

For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.

In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.

Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.

Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
 

Clinical trials underway

There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.

In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).

Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.

The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.

“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”

But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
 

Demand may burden health systems

Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.

“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”

There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.

Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.

“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.

Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.

The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
 

Planning and prep in Boston

In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.

“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”

Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.

“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.

“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.

Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
 

Out-of-pocket test may widen disparities in care

With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.

Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.

There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
 

The first positive test result

Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.

All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”

There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”

Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”

Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.

Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.

Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.

These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.

For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.

In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.

Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.

Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
 

Clinical trials underway

There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.

In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).

Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.

The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.

“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”

But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
 

Demand may burden health systems

Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.

“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”

There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.

Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.

“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.

Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.

The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
 

Planning and prep in Boston

In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.

“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”

Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.

“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.

“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.

Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
 

Out-of-pocket test may widen disparities in care

With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.

Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.

There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
 

The first positive test result

Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.

All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”

There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”

Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”

Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.

Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.

Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.

These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.

For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.

In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.

Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.

Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
 

Clinical trials underway

There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.

In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).

Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.

The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.

“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”

But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
 

Demand may burden health systems

Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.

“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”

There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.

Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.

“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.

Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.

The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
 

Planning and prep in Boston

In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.

“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”

Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.

“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.

“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.

Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
 

Out-of-pocket test may widen disparities in care

With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.

Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.

There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
 

The first positive test result

Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.

All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”

There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”

Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”

Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.

Breast cancer treatments have made great strides in recent years with significant reductions in overall mortality. However, the incidence of breast cancer has increased just slightly in recent years after a dip in the early 2000s.

“The good news is that mortality is decreasing, but it still remains high. We still have a long way to go to tackle this problem of breast cancer incidence as well as the number of deaths,” said Angela DeMichele, MD, co-leader of the breast cancer research program at the University of Pennsylvania’s Abramson Cancer Center. She participated in a session on obstacles in breast cancer treatment held in December at the San Antonio Breast Cancer Symposium. She joined other oncologists in outlining key challenges that need to be addressed to improve breast cancer diagnosis and treatment.

They highlighted six obstacles: The need for more prevention/early detection strategies; the underutilization of artificial intelligence; underuse of precision oncology such as targeted therapies; the need for innovation in clinical trials; a widening gap in cancer disparities; and the need to align incentives and funding for research collaboration, training, and retention.

Since 2012, the Food and Drug Administration has approved 20 new therapeutics to treat breast cancer. Nadia Harbeck, MD, PhD, director of the breast center at LMU University Hospital, Munich, said that the development of new therapies has in a way become a victim of its own success. Therapies and survival have improved, making it harder to compare novel therapies to the standard of care and prove a benefit. Treatment guidelines are changing so quickly that clinical trials are sometimes obsolete by the time they are published because of changes to the standard of care. That places a need on more real-world evidence that can be designed to be useful in the clinic, and AI can help here. “We need to convince regulators to act upon cleverly planned real world evidence analysis. You can randomize them, you can use registries, and you should also be able to change labels because of [new] data,” Dr. Harbeck said.

There are many risk factors that drive breast cancer, and it is very heterogeneous, said Christine Ambrosone, PhD, chair of the department of cancer prevention and control at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y. She called for identifying patients who are at risk for a poor prognosis, such as patients with hormone receptor–negative breast cancer, high-grade, and triple-negative breast cancer. Otherwise there is a risk of overtreatment of low-risk tumors, which could potentially be identified with new tools in precision oncology such as liquid biopsy tests, also known as multicancer early detection tests. These tests can detect cancers long before they become symptomatic. The first such test was launched this year and many more are in clinical trials.

Regina Barzilay, PhD, professor and expert in the use of artificial intelligence in health at the Massachusetts Institute of Technology, pointed out that machine learning is used in many fields, but hardly at all in breast cancer. It could be applied to data on biomarkers and other factors collected from retrospective analyses and clinical trials. She added that machine learning is often applied to biochemistry and single cell analysis of other tumor types, but rarely in breast cancer. “It is severely underutilized,” Dr. Barzilay said. One challenge is that researchers are not necessarily familiar with the techniques of machine learning and AI. Another issue is that breast cancer data are not easy to share and may not be readily available to AI researchers. “An investment in interchangeable data is crucially important,” she said.

Artificial intelligence could assist in identifying and modeling factors that contribute to cancer risk by teasing apart complicated relationships, such as the association between pregnancy, breastfeeding, and breast cancer risk. Pregnancy reduces the risk of hormone receptor–positive disease, but increases the risk of hormone receptor–negative disease.

Another key challenge is the underuse of “omics” technologies, which measure large scale patterns in biological characteristics such as gene variation or protein expression. That has roots in the history of breast cancer being considered as a separate entity from other solid tumors such as lung or pancreatic cancer. Fabrice André, MD, PhD, an oncologist with Gustave Roussy Cancer Center, France, emphasized that breast cancer shouldn’t be considered an entity when it’s metastatic. Instead, tumors should be defined by molecular characteristics they share. He anticipates a personalized medicine future where academic and industry groups collaborate to create an individualized therapy for patients based on genetic factors.
 

Access to therapies for all patients

Novel and effective therapies can make a difference only if patients have access to them, and a key obstacle to improving breast cancer care is racism and inequities in health care. “We have to acknowledge that there is racism in medicine. I think once we acknowledge that, then we can look at things in our practices that we need to change. We can think very broadly and look at things that perhaps disadvantage one population over another,” said Lori Pierce, MD, a radiation oncologist with the University of Michigan, Ann Arbor.

Dr. Pierce also emphasized the need to recruit more underrepresented groups to participate in clinical trials. For example, of six breast cancer clinical trials – for margetuximab (Margenza), sacituzumab govitecan (Trodelvy), tucatinib (Tukysa), trastuzumab deruxtecan (Enhertu), alpelisib (Piqray), and talazoparib (Talzenna), only a small percentage included Black, Asian, and Hispanic women. For trastuzumab deruxtecan, which is widely recognized as a best-in-class HER2-targeting antibody drug conjugate, 51% were White, 42% Asian, 6% Hispanic, and 3% Black. For sacituzumab govitecan, a blockbuster drug for triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer that disproportionately affects Black women, only 7% of women enrolled in clinical trials were Black. In clinical trials for margetuximab, approved to treat HER2-positive breast cancer, 80% of participants were White, 5% Black, 6% Asian, and 9% Hispanic.

There is a perception that minorities may be unwilling to participate in clinical trials, but that’s not true, according to Patty Spears, a research manager of the Patient Advocates for Research Council at the University of North Carolina. “We know that there are data that clearly show that patients will go on clinical trials at the same rate, whether they’re Black, White, Asian, or whatever. You have to be able to have them in your system and ask them to go on trial,” she said.

Another panelist told a personal anecdote to illustrate the point. Matthew Ellis, MD, PhD, recalled that he spent 13 years at Washington University in St. Louis, serving one of the more segregated cities in the United States. The city hospital closed, and Washington University and the Siteman Cancer Center signed a contract to treat the underserved population that was suddenly without a source of care. “Subsequent to that, we over-accrued relative to the population of African American patients. What that taught me is it’s nothing to do with the lack of willingness of African Americans to participate in clinical trials. Quite the opposite. It’s the question of access to clinical trials, access to great care, and not creating health care systems that segregate patients into places where they’re not getting access,” he said.

Breast cancer treatments have made great strides in recent years with significant reductions in overall mortality. However, the incidence of breast cancer has increased just slightly in recent years after a dip in the early 2000s.

“The good news is that mortality is decreasing, but it still remains high. We still have a long way to go to tackle this problem of breast cancer incidence as well as the number of deaths,” said Angela DeMichele, MD, co-leader of the breast cancer research program at the University of Pennsylvania’s Abramson Cancer Center. She participated in a session on obstacles in breast cancer treatment held in December at the San Antonio Breast Cancer Symposium. She joined other oncologists in outlining key challenges that need to be addressed to improve breast cancer diagnosis and treatment.

They highlighted six obstacles: The need for more prevention/early detection strategies; the underutilization of artificial intelligence; underuse of precision oncology such as targeted therapies; the need for innovation in clinical trials; a widening gap in cancer disparities; and the need to align incentives and funding for research collaboration, training, and retention.

Since 2012, the Food and Drug Administration has approved 20 new therapeutics to treat breast cancer. Nadia Harbeck, MD, PhD, director of the breast center at LMU University Hospital, Munich, said that the development of new therapies has in a way become a victim of its own success. Therapies and survival have improved, making it harder to compare novel therapies to the standard of care and prove a benefit. Treatment guidelines are changing so quickly that clinical trials are sometimes obsolete by the time they are published because of changes to the standard of care. That places a need on more real-world evidence that can be designed to be useful in the clinic, and AI can help here. “We need to convince regulators to act upon cleverly planned real world evidence analysis. You can randomize them, you can use registries, and you should also be able to change labels because of [new] data,” Dr. Harbeck said.

There are many risk factors that drive breast cancer, and it is very heterogeneous, said Christine Ambrosone, PhD, chair of the department of cancer prevention and control at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y. She called for identifying patients who are at risk for a poor prognosis, such as patients with hormone receptor–negative breast cancer, high-grade, and triple-negative breast cancer. Otherwise there is a risk of overtreatment of low-risk tumors, which could potentially be identified with new tools in precision oncology such as liquid biopsy tests, also known as multicancer early detection tests. These tests can detect cancers long before they become symptomatic. The first such test was launched this year and many more are in clinical trials.

Regina Barzilay, PhD, professor and expert in the use of artificial intelligence in health at the Massachusetts Institute of Technology, pointed out that machine learning is used in many fields, but hardly at all in breast cancer. It could be applied to data on biomarkers and other factors collected from retrospective analyses and clinical trials. She added that machine learning is often applied to biochemistry and single cell analysis of other tumor types, but rarely in breast cancer. “It is severely underutilized,” Dr. Barzilay said. One challenge is that researchers are not necessarily familiar with the techniques of machine learning and AI. Another issue is that breast cancer data are not easy to share and may not be readily available to AI researchers. “An investment in interchangeable data is crucially important,” she said.

Artificial intelligence could assist in identifying and modeling factors that contribute to cancer risk by teasing apart complicated relationships, such as the association between pregnancy, breastfeeding, and breast cancer risk. Pregnancy reduces the risk of hormone receptor–positive disease, but increases the risk of hormone receptor–negative disease.

Another key challenge is the underuse of “omics” technologies, which measure large scale patterns in biological characteristics such as gene variation or protein expression. That has roots in the history of breast cancer being considered as a separate entity from other solid tumors such as lung or pancreatic cancer. Fabrice André, MD, PhD, an oncologist with Gustave Roussy Cancer Center, France, emphasized that breast cancer shouldn’t be considered an entity when it’s metastatic. Instead, tumors should be defined by molecular characteristics they share. He anticipates a personalized medicine future where academic and industry groups collaborate to create an individualized therapy for patients based on genetic factors.
 

Access to therapies for all patients

Novel and effective therapies can make a difference only if patients have access to them, and a key obstacle to improving breast cancer care is racism and inequities in health care. “We have to acknowledge that there is racism in medicine. I think once we acknowledge that, then we can look at things in our practices that we need to change. We can think very broadly and look at things that perhaps disadvantage one population over another,” said Lori Pierce, MD, a radiation oncologist with the University of Michigan, Ann Arbor.

Dr. Pierce also emphasized the need to recruit more underrepresented groups to participate in clinical trials. For example, of six breast cancer clinical trials – for margetuximab (Margenza), sacituzumab govitecan (Trodelvy), tucatinib (Tukysa), trastuzumab deruxtecan (Enhertu), alpelisib (Piqray), and talazoparib (Talzenna), only a small percentage included Black, Asian, and Hispanic women. For trastuzumab deruxtecan, which is widely recognized as a best-in-class HER2-targeting antibody drug conjugate, 51% were White, 42% Asian, 6% Hispanic, and 3% Black. For sacituzumab govitecan, a blockbuster drug for triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer that disproportionately affects Black women, only 7% of women enrolled in clinical trials were Black. In clinical trials for margetuximab, approved to treat HER2-positive breast cancer, 80% of participants were White, 5% Black, 6% Asian, and 9% Hispanic.

There is a perception that minorities may be unwilling to participate in clinical trials, but that’s not true, according to Patty Spears, a research manager of the Patient Advocates for Research Council at the University of North Carolina. “We know that there are data that clearly show that patients will go on clinical trials at the same rate, whether they’re Black, White, Asian, or whatever. You have to be able to have them in your system and ask them to go on trial,” she said.

Another panelist told a personal anecdote to illustrate the point. Matthew Ellis, MD, PhD, recalled that he spent 13 years at Washington University in St. Louis, serving one of the more segregated cities in the United States. The city hospital closed, and Washington University and the Siteman Cancer Center signed a contract to treat the underserved population that was suddenly without a source of care. “Subsequent to that, we over-accrued relative to the population of African American patients. What that taught me is it’s nothing to do with the lack of willingness of African Americans to participate in clinical trials. Quite the opposite. It’s the question of access to clinical trials, access to great care, and not creating health care systems that segregate patients into places where they’re not getting access,” he said.

Breast cancer treatments have made great strides in recent years with significant reductions in overall mortality. However, the incidence of breast cancer has increased just slightly in recent years after a dip in the early 2000s.

“The good news is that mortality is decreasing, but it still remains high. We still have a long way to go to tackle this problem of breast cancer incidence as well as the number of deaths,” said Angela DeMichele, MD, co-leader of the breast cancer research program at the University of Pennsylvania’s Abramson Cancer Center. She participated in a session on obstacles in breast cancer treatment held in December at the San Antonio Breast Cancer Symposium. She joined other oncologists in outlining key challenges that need to be addressed to improve breast cancer diagnosis and treatment.

They highlighted six obstacles: The need for more prevention/early detection strategies; the underutilization of artificial intelligence; underuse of precision oncology such as targeted therapies; the need for innovation in clinical trials; a widening gap in cancer disparities; and the need to align incentives and funding for research collaboration, training, and retention.

Since 2012, the Food and Drug Administration has approved 20 new therapeutics to treat breast cancer. Nadia Harbeck, MD, PhD, director of the breast center at LMU University Hospital, Munich, said that the development of new therapies has in a way become a victim of its own success. Therapies and survival have improved, making it harder to compare novel therapies to the standard of care and prove a benefit. Treatment guidelines are changing so quickly that clinical trials are sometimes obsolete by the time they are published because of changes to the standard of care. That places a need on more real-world evidence that can be designed to be useful in the clinic, and AI can help here. “We need to convince regulators to act upon cleverly planned real world evidence analysis. You can randomize them, you can use registries, and you should also be able to change labels because of [new] data,” Dr. Harbeck said.

There are many risk factors that drive breast cancer, and it is very heterogeneous, said Christine Ambrosone, PhD, chair of the department of cancer prevention and control at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y. She called for identifying patients who are at risk for a poor prognosis, such as patients with hormone receptor–negative breast cancer, high-grade, and triple-negative breast cancer. Otherwise there is a risk of overtreatment of low-risk tumors, which could potentially be identified with new tools in precision oncology such as liquid biopsy tests, also known as multicancer early detection tests. These tests can detect cancers long before they become symptomatic. The first such test was launched this year and many more are in clinical trials.

Regina Barzilay, PhD, professor and expert in the use of artificial intelligence in health at the Massachusetts Institute of Technology, pointed out that machine learning is used in many fields, but hardly at all in breast cancer. It could be applied to data on biomarkers and other factors collected from retrospective analyses and clinical trials. She added that machine learning is often applied to biochemistry and single cell analysis of other tumor types, but rarely in breast cancer. “It is severely underutilized,” Dr. Barzilay said. One challenge is that researchers are not necessarily familiar with the techniques of machine learning and AI. Another issue is that breast cancer data are not easy to share and may not be readily available to AI researchers. “An investment in interchangeable data is crucially important,” she said.

Artificial intelligence could assist in identifying and modeling factors that contribute to cancer risk by teasing apart complicated relationships, such as the association between pregnancy, breastfeeding, and breast cancer risk. Pregnancy reduces the risk of hormone receptor–positive disease, but increases the risk of hormone receptor–negative disease.

Another key challenge is the underuse of “omics” technologies, which measure large scale patterns in biological characteristics such as gene variation or protein expression. That has roots in the history of breast cancer being considered as a separate entity from other solid tumors such as lung or pancreatic cancer. Fabrice André, MD, PhD, an oncologist with Gustave Roussy Cancer Center, France, emphasized that breast cancer shouldn’t be considered an entity when it’s metastatic. Instead, tumors should be defined by molecular characteristics they share. He anticipates a personalized medicine future where academic and industry groups collaborate to create an individualized therapy for patients based on genetic factors.
 

Access to therapies for all patients

Novel and effective therapies can make a difference only if patients have access to them, and a key obstacle to improving breast cancer care is racism and inequities in health care. “We have to acknowledge that there is racism in medicine. I think once we acknowledge that, then we can look at things in our practices that we need to change. We can think very broadly and look at things that perhaps disadvantage one population over another,” said Lori Pierce, MD, a radiation oncologist with the University of Michigan, Ann Arbor.

Dr. Pierce also emphasized the need to recruit more underrepresented groups to participate in clinical trials. For example, of six breast cancer clinical trials – for margetuximab (Margenza), sacituzumab govitecan (Trodelvy), tucatinib (Tukysa), trastuzumab deruxtecan (Enhertu), alpelisib (Piqray), and talazoparib (Talzenna), only a small percentage included Black, Asian, and Hispanic women. For trastuzumab deruxtecan, which is widely recognized as a best-in-class HER2-targeting antibody drug conjugate, 51% were White, 42% Asian, 6% Hispanic, and 3% Black. For sacituzumab govitecan, a blockbuster drug for triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer that disproportionately affects Black women, only 7% of women enrolled in clinical trials were Black. In clinical trials for margetuximab, approved to treat HER2-positive breast cancer, 80% of participants were White, 5% Black, 6% Asian, and 9% Hispanic.

There is a perception that minorities may be unwilling to participate in clinical trials, but that’s not true, according to Patty Spears, a research manager of the Patient Advocates for Research Council at the University of North Carolina. “We know that there are data that clearly show that patients will go on clinical trials at the same rate, whether they’re Black, White, Asian, or whatever. You have to be able to have them in your system and ask them to go on trial,” she said.

Another panelist told a personal anecdote to illustrate the point. Matthew Ellis, MD, PhD, recalled that he spent 13 years at Washington University in St. Louis, serving one of the more segregated cities in the United States. The city hospital closed, and Washington University and the Siteman Cancer Center signed a contract to treat the underserved population that was suddenly without a source of care. “Subsequent to that, we over-accrued relative to the population of African American patients. What that taught me is it’s nothing to do with the lack of willingness of African Americans to participate in clinical trials. Quite the opposite. It’s the question of access to clinical trials, access to great care, and not creating health care systems that segregate patients into places where they’re not getting access,” he said.

Findings from the LymphVAX study recently presented at the San Antonio Breast Cancer Symposium show that relatively few women with breast cancer who are at risk for lymphedema develop lymph node swelling after receiving an mRNA COVID-19 vaccine.

Lymph node swelling can be a particularly troubling side effect, since it could be mistaken for breast cancer progression. In this study, of 621 women who received the first dose of an mRNA COVID-19 vaccine, 9.8% developed lymph node swelling as compared with 12.9% of 621 women who received the second dose, and 11.3% of 469 women who received the third dose. The findings were comparable to those of studies conducted of the general population, said study author Brooke C. Juhel, BS, a clinical research coordinator in the lymphedema research program at Massachusetts General Hospital and a student at Harvard Medical School, both in Boston. In the general population, 10.2% experienced lymph node swelling after the first dose and 14% after the second dose, according to the Centers for Disease Control and studies of the Pfizer and Moderna vaccines.

“This is consistent with the hypothesis that, after repeated vaccine doses, the immune system already has the antigens ready to fight the virus, thus the side effects may worsen as the immune response has increased,” she said. “Having screened over 6,500 women for breast cancer–related lymphedema, and with our patients reaching out with concerns about vaccine side effects, we were in a unique position to conduct this study.”

The study also confirmed that the most common side effects of receiving mRNA COVID-19 vaccines for women treated for breast cancer included injection site soreness, fatigue, muscle soreness, headache and chills lasting an average of 48 hours, which are symptoms comparable with those experienced by the general population.

“The side-effect profiles reported in this study for a cohort of women treated for breast cancer can be used to provide evidence-based patient education regarding future COVID-19 vaccine administration. The effect of the COVID-19 vaccines on breast cancer–related lymphedema risk is currently unknown and more research is required. In the interim, we would recommend vaccination away from the side of lymph node removal, either in the contralateral arm or in the thigh,” Ms. Juhel said.

The median duration of lymph node swelling was less than 1 week. In cases where lymph node swelling occurred after the first dose, 54.1% had swelling in ipsilateral axillary lymph nodes, and 45.9% in contralateral axillary lymph nodes. About 29.5% experienced swelling in ipsilateral supraclavicular lymph nodes, and 18.0% in contralateral supraclavicular lymph nodes.

Injection-site soreness, fatigue, GMS, headache, and chills occurred less often among older individuals (P < .001), and fatigue, muscle soreness, headache, and chills occurred more frequently after the second dose than the first (P < .001). The median duration of all side effects was 48 hours or less.

“The informed education that can be produced based on these results will hopefully ease the fears of women treated for breast cancer and empower them to make informed decisions regarding future vaccine doses,” Ms. Juhel said.

Ms. Juhel has no relevant financial disclosures.

Findings from the LymphVAX study recently presented at the San Antonio Breast Cancer Symposium show that relatively few women with breast cancer who are at risk for lymphedema develop lymph node swelling after receiving an mRNA COVID-19 vaccine.

Lymph node swelling can be a particularly troubling side effect, since it could be mistaken for breast cancer progression. In this study, of 621 women who received the first dose of an mRNA COVID-19 vaccine, 9.8% developed lymph node swelling as compared with 12.9% of 621 women who received the second dose, and 11.3% of 469 women who received the third dose. The findings were comparable to those of studies conducted of the general population, said study author Brooke C. Juhel, BS, a clinical research coordinator in the lymphedema research program at Massachusetts General Hospital and a student at Harvard Medical School, both in Boston. In the general population, 10.2% experienced lymph node swelling after the first dose and 14% after the second dose, according to the Centers for Disease Control and studies of the Pfizer and Moderna vaccines.

“This is consistent with the hypothesis that, after repeated vaccine doses, the immune system already has the antigens ready to fight the virus, thus the side effects may worsen as the immune response has increased,” she said. “Having screened over 6,500 women for breast cancer–related lymphedema, and with our patients reaching out with concerns about vaccine side effects, we were in a unique position to conduct this study.”

The study also confirmed that the most common side effects of receiving mRNA COVID-19 vaccines for women treated for breast cancer included injection site soreness, fatigue, muscle soreness, headache and chills lasting an average of 48 hours, which are symptoms comparable with those experienced by the general population.

“The side-effect profiles reported in this study for a cohort of women treated for breast cancer can be used to provide evidence-based patient education regarding future COVID-19 vaccine administration. The effect of the COVID-19 vaccines on breast cancer–related lymphedema risk is currently unknown and more research is required. In the interim, we would recommend vaccination away from the side of lymph node removal, either in the contralateral arm or in the thigh,” Ms. Juhel said.

The median duration of lymph node swelling was less than 1 week. In cases where lymph node swelling occurred after the first dose, 54.1% had swelling in ipsilateral axillary lymph nodes, and 45.9% in contralateral axillary lymph nodes. About 29.5% experienced swelling in ipsilateral supraclavicular lymph nodes, and 18.0% in contralateral supraclavicular lymph nodes.

Injection-site soreness, fatigue, GMS, headache, and chills occurred less often among older individuals (P < .001), and fatigue, muscle soreness, headache, and chills occurred more frequently after the second dose than the first (P < .001). The median duration of all side effects was 48 hours or less.

“The informed education that can be produced based on these results will hopefully ease the fears of women treated for breast cancer and empower them to make informed decisions regarding future vaccine doses,” Ms. Juhel said.

Ms. Juhel has no relevant financial disclosures.

Findings from the LymphVAX study recently presented at the San Antonio Breast Cancer Symposium show that relatively few women with breast cancer who are at risk for lymphedema develop lymph node swelling after receiving an mRNA COVID-19 vaccine.

Lymph node swelling can be a particularly troubling side effect, since it could be mistaken for breast cancer progression. In this study, of 621 women who received the first dose of an mRNA COVID-19 vaccine, 9.8% developed lymph node swelling as compared with 12.9% of 621 women who received the second dose, and 11.3% of 469 women who received the third dose. The findings were comparable to those of studies conducted of the general population, said study author Brooke C. Juhel, BS, a clinical research coordinator in the lymphedema research program at Massachusetts General Hospital and a student at Harvard Medical School, both in Boston. In the general population, 10.2% experienced lymph node swelling after the first dose and 14% after the second dose, according to the Centers for Disease Control and studies of the Pfizer and Moderna vaccines.

“This is consistent with the hypothesis that, after repeated vaccine doses, the immune system already has the antigens ready to fight the virus, thus the side effects may worsen as the immune response has increased,” she said. “Having screened over 6,500 women for breast cancer–related lymphedema, and with our patients reaching out with concerns about vaccine side effects, we were in a unique position to conduct this study.”

The study also confirmed that the most common side effects of receiving mRNA COVID-19 vaccines for women treated for breast cancer included injection site soreness, fatigue, muscle soreness, headache and chills lasting an average of 48 hours, which are symptoms comparable with those experienced by the general population.

“The side-effect profiles reported in this study for a cohort of women treated for breast cancer can be used to provide evidence-based patient education regarding future COVID-19 vaccine administration. The effect of the COVID-19 vaccines on breast cancer–related lymphedema risk is currently unknown and more research is required. In the interim, we would recommend vaccination away from the side of lymph node removal, either in the contralateral arm or in the thigh,” Ms. Juhel said.

The median duration of lymph node swelling was less than 1 week. In cases where lymph node swelling occurred after the first dose, 54.1% had swelling in ipsilateral axillary lymph nodes, and 45.9% in contralateral axillary lymph nodes. About 29.5% experienced swelling in ipsilateral supraclavicular lymph nodes, and 18.0% in contralateral supraclavicular lymph nodes.

Injection-site soreness, fatigue, GMS, headache, and chills occurred less often among older individuals (P < .001), and fatigue, muscle soreness, headache, and chills occurred more frequently after the second dose than the first (P < .001). The median duration of all side effects was 48 hours or less.

“The informed education that can be produced based on these results will hopefully ease the fears of women treated for breast cancer and empower them to make informed decisions regarding future vaccine doses,” Ms. Juhel said.

Ms. Juhel has no relevant financial disclosures.

In a series of studies recently presented at the San Antonio Breast Cancer Symposium that examine the effects of the COVID-19 pandemic on women with breast cancer, researchers report that ethnicity played a role in later diagnoses, Hispanics presented with more advanced and aggressive disease, and a focus on a single hospital in San Antonio finds a statistical difference between stage at diagnosis prior to the pandemic, compared with the postvaccine era.

Patients treated at the Mays Cancer Center, a cancer hospital of University of Texas Health and MD Anderson Cancer Center in San Antonio, during the pandemic were found to more likely present with advanced disease between March and December 2020, according to Marcela Mazo, MD, an oncologist with UT Health, San Antonio, and an author of each of three studies.

“We learned that Hispanic patients were presenting with more aggressive histologies such as HER2-positive and triple-negative disease. We also confirmed what we were suspecting, which is that Latina women had less access to medical coverage. We had a higher proportion of Hispanic patients presenting to us without medical coverage, which of course made the treatment extremely challenging,” said Dr. Mazo.

Hispanics are one of the fastest-growing minority groups in the United States, and understanding the factors that affect their healthcare is critical to formulating health policies.

“The findings confirmed my suspicion that most patients did not get a mammogram during the lockdown. And I’m sad to say that, even after everything opened up and people could get vaccinated, I still saw some patients who, for whatever reason, did not get a mammogram – which led to [more] clinical presentations of advanced cancer by the time they were seen by us,” she said.

Dr. Mazo said that underscreened women could also be considered victims of the pandemic. “I tell my patients to get their vaccines so they’re protected and they can feel more comfortable going to the doctor where there is a higher proportion of people who could potentially have COVID.”

Other studies have shown that patients in general, regardless of race or ethnicity, have been diagnosed with later-stage breast cancer diagnoses during the pandemic.

The three studies are based on an analysis of 696 patients treated at Mays Cancer Center. Of these, 264 were diagnosed before the pandemic (cohort A), 171 during the lockdown (Apr. 1 to Dec. 31, 2020, cohort B) and 261 after vaccines were introduced (Jan. 1 to Dec. 31, 2021, cohort C). Overall, there was a slight trend toward a higher incidence of HER2-positive disease during the lockdown period (odds ratio, 1.45) and in the postvaccine period (OR, 1.40), though neither relationship was statistically significant (P = .2). No relationships were seen between time period and incidence of triple-negative breast cancer.

The researchers found that Hispanic patients were more likely to be diagnosed with advanced disease in the pandemic years, compared with pre-COVID times. For example, the likelihood of being diagnosed with carcinoma in situ (Tis) versus T1 disease was lower in the postvaccine era than the pre-COVID era (OR, 0.38; P < .001), although there was no significant difference in Tis versus T1 during the lockdown period, compared with the pre-COVID era. The researchers concluded the difference was likely caused by the latency period of breast cancer.

The postvaccine era saw a 15% increase in patients diagnosed with HER2-positive disease, compared with the pre-COVID era. Patients diagnosed in the COVID era (cohorts B and C) were more likely to require neoadjuvant therapy than patients diagnosed in the pre-COVID era (OR, 1.78; P = .009).

They also found significant disparities in health insurance coverage. 91% of non-Hispanic patients were covered by insurance, compared with 70% of Hispanic patients.

Overall, the findings hint at the depth of health care inequities faced by Hispanic women in the region, and should be a call for action, Dr. Mazo said. “I wish that we as physicians would take the lead to do the best we can to support legislative changes that could help all of our patients get treated – independent of where they come from.”

Dr. Mazo has no relevant financial disclosures.

In a series of studies recently presented at the San Antonio Breast Cancer Symposium that examine the effects of the COVID-19 pandemic on women with breast cancer, researchers report that ethnicity played a role in later diagnoses, Hispanics presented with more advanced and aggressive disease, and a focus on a single hospital in San Antonio finds a statistical difference between stage at diagnosis prior to the pandemic, compared with the postvaccine era.

Patients treated at the Mays Cancer Center, a cancer hospital of University of Texas Health and MD Anderson Cancer Center in San Antonio, during the pandemic were found to more likely present with advanced disease between March and December 2020, according to Marcela Mazo, MD, an oncologist with UT Health, San Antonio, and an author of each of three studies.

“We learned that Hispanic patients were presenting with more aggressive histologies such as HER2-positive and triple-negative disease. We also confirmed what we were suspecting, which is that Latina women had less access to medical coverage. We had a higher proportion of Hispanic patients presenting to us without medical coverage, which of course made the treatment extremely challenging,” said Dr. Mazo.

Hispanics are one of the fastest-growing minority groups in the United States, and understanding the factors that affect their healthcare is critical to formulating health policies.

“The findings confirmed my suspicion that most patients did not get a mammogram during the lockdown. And I’m sad to say that, even after everything opened up and people could get vaccinated, I still saw some patients who, for whatever reason, did not get a mammogram – which led to [more] clinical presentations of advanced cancer by the time they were seen by us,” she said.

Dr. Mazo said that underscreened women could also be considered victims of the pandemic. “I tell my patients to get their vaccines so they’re protected and they can feel more comfortable going to the doctor where there is a higher proportion of people who could potentially have COVID.”

Other studies have shown that patients in general, regardless of race or ethnicity, have been diagnosed with later-stage breast cancer diagnoses during the pandemic.

The three studies are based on an analysis of 696 patients treated at Mays Cancer Center. Of these, 264 were diagnosed before the pandemic (cohort A), 171 during the lockdown (Apr. 1 to Dec. 31, 2020, cohort B) and 261 after vaccines were introduced (Jan. 1 to Dec. 31, 2021, cohort C). Overall, there was a slight trend toward a higher incidence of HER2-positive disease during the lockdown period (odds ratio, 1.45) and in the postvaccine period (OR, 1.40), though neither relationship was statistically significant (P = .2). No relationships were seen between time period and incidence of triple-negative breast cancer.

The researchers found that Hispanic patients were more likely to be diagnosed with advanced disease in the pandemic years, compared with pre-COVID times. For example, the likelihood of being diagnosed with carcinoma in situ (Tis) versus T1 disease was lower in the postvaccine era than the pre-COVID era (OR, 0.38; P < .001), although there was no significant difference in Tis versus T1 during the lockdown period, compared with the pre-COVID era. The researchers concluded the difference was likely caused by the latency period of breast cancer.

The postvaccine era saw a 15% increase in patients diagnosed with HER2-positive disease, compared with the pre-COVID era. Patients diagnosed in the COVID era (cohorts B and C) were more likely to require neoadjuvant therapy than patients diagnosed in the pre-COVID era (OR, 1.78; P = .009).

They also found significant disparities in health insurance coverage. 91% of non-Hispanic patients were covered by insurance, compared with 70% of Hispanic patients.

Overall, the findings hint at the depth of health care inequities faced by Hispanic women in the region, and should be a call for action, Dr. Mazo said. “I wish that we as physicians would take the lead to do the best we can to support legislative changes that could help all of our patients get treated – independent of where they come from.”

Dr. Mazo has no relevant financial disclosures.

In a series of studies recently presented at the San Antonio Breast Cancer Symposium that examine the effects of the COVID-19 pandemic on women with breast cancer, researchers report that ethnicity played a role in later diagnoses, Hispanics presented with more advanced and aggressive disease, and a focus on a single hospital in San Antonio finds a statistical difference between stage at diagnosis prior to the pandemic, compared with the postvaccine era.

Patients treated at the Mays Cancer Center, a cancer hospital of University of Texas Health and MD Anderson Cancer Center in San Antonio, during the pandemic were found to more likely present with advanced disease between March and December 2020, according to Marcela Mazo, MD, an oncologist with UT Health, San Antonio, and an author of each of three studies.

“We learned that Hispanic patients were presenting with more aggressive histologies such as HER2-positive and triple-negative disease. We also confirmed what we were suspecting, which is that Latina women had less access to medical coverage. We had a higher proportion of Hispanic patients presenting to us without medical coverage, which of course made the treatment extremely challenging,” said Dr. Mazo.

Hispanics are one of the fastest-growing minority groups in the United States, and understanding the factors that affect their healthcare is critical to formulating health policies.

“The findings confirmed my suspicion that most patients did not get a mammogram during the lockdown. And I’m sad to say that, even after everything opened up and people could get vaccinated, I still saw some patients who, for whatever reason, did not get a mammogram – which led to [more] clinical presentations of advanced cancer by the time they were seen by us,” she said.

Dr. Mazo said that underscreened women could also be considered victims of the pandemic. “I tell my patients to get their vaccines so they’re protected and they can feel more comfortable going to the doctor where there is a higher proportion of people who could potentially have COVID.”

Other studies have shown that patients in general, regardless of race or ethnicity, have been diagnosed with later-stage breast cancer diagnoses during the pandemic.

The three studies are based on an analysis of 696 patients treated at Mays Cancer Center. Of these, 264 were diagnosed before the pandemic (cohort A), 171 during the lockdown (Apr. 1 to Dec. 31, 2020, cohort B) and 261 after vaccines were introduced (Jan. 1 to Dec. 31, 2021, cohort C). Overall, there was a slight trend toward a higher incidence of HER2-positive disease during the lockdown period (odds ratio, 1.45) and in the postvaccine period (OR, 1.40), though neither relationship was statistically significant (P = .2). No relationships were seen between time period and incidence of triple-negative breast cancer.

The researchers found that Hispanic patients were more likely to be diagnosed with advanced disease in the pandemic years, compared with pre-COVID times. For example, the likelihood of being diagnosed with carcinoma in situ (Tis) versus T1 disease was lower in the postvaccine era than the pre-COVID era (OR, 0.38; P < .001), although there was no significant difference in Tis versus T1 during the lockdown period, compared with the pre-COVID era. The researchers concluded the difference was likely caused by the latency period of breast cancer.

The postvaccine era saw a 15% increase in patients diagnosed with HER2-positive disease, compared with the pre-COVID era. Patients diagnosed in the COVID era (cohorts B and C) were more likely to require neoadjuvant therapy than patients diagnosed in the pre-COVID era (OR, 1.78; P = .009).

They also found significant disparities in health insurance coverage. 91% of non-Hispanic patients were covered by insurance, compared with 70% of Hispanic patients.

Overall, the findings hint at the depth of health care inequities faced by Hispanic women in the region, and should be a call for action, Dr. Mazo said. “I wish that we as physicians would take the lead to do the best we can to support legislative changes that could help all of our patients get treated – independent of where they come from.”

Dr. Mazo has no relevant financial disclosures.

A new study recently presented at the San Antonio Breast Cancer Symposium found that patients in economically and racially/ethnically marginalized neighborhoods are more likely to present with breast cancer at later stages of the disease.

“Neighborhood economic status and residential segregation can shape cancer outcomes such as later-stage diagnosis through several mechanisms, such as access to health care, particularly through limited breast cancer mammographic screening,” said the study’s author, Neha Goel, MD, an assistant professor of surgery at the University of Miami.

The findings are based on an analysis of data from the neighborhood indicator called the Index of Concentration at the Extremes, a database that focuses on the distribution of concentrations of privilege and deprivation, rather than comparing individual or household levels. This is important because growing concentrations of extreme wealth and extreme poverty are becoming increasingly common, and these are not properties discernible by measures by individuals or households. The indicator considers concentration of privilege and deprivation independently, unlike typical models that combine these factors. Doing so reduces bias that can occur in statistical models where these two factors can influence one another. “It brings subtle social inequalities and polarization to the forefront and maps a critical dimension of social inequality,” Dr. Goel said.

Researchers defined structural racism based on its effects, such as separation of marginalized economic and racial/ethnic groups, as well as classism that occurs as a result of discriminatory housing policies over decades. The American Medical Association defines structural racism as the “totality of ways in which societies foster racial discrimination through mutually reinforcing systems of housing, education, employment, earnings, benefits, credit, media, health care and criminal justice.” It considers racism, structural racism, and unconscious biases within medical research and health care delivery to be public health threats. The AMA calls for educational and continuing medical education programs to promote an understanding of all forms of racism, and methods for preventing or reducing the health effects of racism.

The final analysis included 6,145 patients (52.6% Hispanic, 26.3 White, and 17.2% Black) who were treated for breast cancer between 2005 and 2017. At 45.2%, nearly half of participants were privately insured.

Five models were created comparing the likelihood of being diagnosed with a more advance stage tumor (stage 3-4 vs. stage 1-2) between the most disadvantage quartile and the most advantaged group quartile. They found significant relationships for low versus high economic segregation for both the most disadvantaged quartile (odds ratio, 1.36; P < .05) and the second-most disadvantaged quartile (OR, 1.43; P < .05); low-income Black versus high-income White patients in both the most disadvantage quartile (OR, 1.55; P < .05) and the second-most disadvantaged quartile (OR, 1.44; P < .05); Hispanic versus non-Hispanic ethnicity in the most disadvantaged quartile (OR, 1.32; P < .05), and low-income Hispanics versus high-income Whites in both the most disadvantaged quartile (OR, 1.43; P < .05) and the second-most disadvantaged quartile (OR, 1.56; P < .05).

Black patients were more likely to be diagnosed with triple-negative breast cancer than White patients (25.1% vs. 12.5%; P < .001).

The findings suggest that both economically disadvantaged patients and those in racially or ethnically marginalized neighborhoods had a greater probability of having later-stage disease at diagnosis. The researchers controlled for age, insurance status, tumor subtype, and comorbidities like diabetes, coronary artery disease, and hyperlipidemia.

“This study adds insight to a growing body of literature that demonstrate how the ecological effects of structural racism – expressed through poverty and residential segregation – shape cancer outcomes across patients of all races [and] ethnicities,” Dr. Goel said.

Dr. Goel has no relevant financial disclosures.

A new study recently presented at the San Antonio Breast Cancer Symposium found that patients in economically and racially/ethnically marginalized neighborhoods are more likely to present with breast cancer at later stages of the disease.

“Neighborhood economic status and residential segregation can shape cancer outcomes such as later-stage diagnosis through several mechanisms, such as access to health care, particularly through limited breast cancer mammographic screening,” said the study’s author, Neha Goel, MD, an assistant professor of surgery at the University of Miami.

The findings are based on an analysis of data from the neighborhood indicator called the Index of Concentration at the Extremes, a database that focuses on the distribution of concentrations of privilege and deprivation, rather than comparing individual or household levels. This is important because growing concentrations of extreme wealth and extreme poverty are becoming increasingly common, and these are not properties discernible by measures by individuals or households. The indicator considers concentration of privilege and deprivation independently, unlike typical models that combine these factors. Doing so reduces bias that can occur in statistical models where these two factors can influence one another. “It brings subtle social inequalities and polarization to the forefront and maps a critical dimension of social inequality,” Dr. Goel said.

Researchers defined structural racism based on its effects, such as separation of marginalized economic and racial/ethnic groups, as well as classism that occurs as a result of discriminatory housing policies over decades. The American Medical Association defines structural racism as the “totality of ways in which societies foster racial discrimination through mutually reinforcing systems of housing, education, employment, earnings, benefits, credit, media, health care and criminal justice.” It considers racism, structural racism, and unconscious biases within medical research and health care delivery to be public health threats. The AMA calls for educational and continuing medical education programs to promote an understanding of all forms of racism, and methods for preventing or reducing the health effects of racism.

The final analysis included 6,145 patients (52.6% Hispanic, 26.3 White, and 17.2% Black) who were treated for breast cancer between 2005 and 2017. At 45.2%, nearly half of participants were privately insured.

Five models were created comparing the likelihood of being diagnosed with a more advance stage tumor (stage 3-4 vs. stage 1-2) between the most disadvantage quartile and the most advantaged group quartile. They found significant relationships for low versus high economic segregation for both the most disadvantaged quartile (odds ratio, 1.36; P < .05) and the second-most disadvantaged quartile (OR, 1.43; P < .05); low-income Black versus high-income White patients in both the most disadvantage quartile (OR, 1.55; P < .05) and the second-most disadvantaged quartile (OR, 1.44; P < .05); Hispanic versus non-Hispanic ethnicity in the most disadvantaged quartile (OR, 1.32; P < .05), and low-income Hispanics versus high-income Whites in both the most disadvantaged quartile (OR, 1.43; P < .05) and the second-most disadvantaged quartile (OR, 1.56; P < .05).

Black patients were more likely to be diagnosed with triple-negative breast cancer than White patients (25.1% vs. 12.5%; P < .001).

The findings suggest that both economically disadvantaged patients and those in racially or ethnically marginalized neighborhoods had a greater probability of having later-stage disease at diagnosis. The researchers controlled for age, insurance status, tumor subtype, and comorbidities like diabetes, coronary artery disease, and hyperlipidemia.

“This study adds insight to a growing body of literature that demonstrate how the ecological effects of structural racism – expressed through poverty and residential segregation – shape cancer outcomes across patients of all races [and] ethnicities,” Dr. Goel said.

Dr. Goel has no relevant financial disclosures.

A new study recently presented at the San Antonio Breast Cancer Symposium found that patients in economically and racially/ethnically marginalized neighborhoods are more likely to present with breast cancer at later stages of the disease.

“Neighborhood economic status and residential segregation can shape cancer outcomes such as later-stage diagnosis through several mechanisms, such as access to health care, particularly through limited breast cancer mammographic screening,” said the study’s author, Neha Goel, MD, an assistant professor of surgery at the University of Miami.

The findings are based on an analysis of data from the neighborhood indicator called the Index of Concentration at the Extremes, a database that focuses on the distribution of concentrations of privilege and deprivation, rather than comparing individual or household levels. This is important because growing concentrations of extreme wealth and extreme poverty are becoming increasingly common, and these are not properties discernible by measures by individuals or households. The indicator considers concentration of privilege and deprivation independently, unlike typical models that combine these factors. Doing so reduces bias that can occur in statistical models where these two factors can influence one another. “It brings subtle social inequalities and polarization to the forefront and maps a critical dimension of social inequality,” Dr. Goel said.

Researchers defined structural racism based on its effects, such as separation of marginalized economic and racial/ethnic groups, as well as classism that occurs as a result of discriminatory housing policies over decades. The American Medical Association defines structural racism as the “totality of ways in which societies foster racial discrimination through mutually reinforcing systems of housing, education, employment, earnings, benefits, credit, media, health care and criminal justice.” It considers racism, structural racism, and unconscious biases within medical research and health care delivery to be public health threats. The AMA calls for educational and continuing medical education programs to promote an understanding of all forms of racism, and methods for preventing or reducing the health effects of racism.

The final analysis included 6,145 patients (52.6% Hispanic, 26.3 White, and 17.2% Black) who were treated for breast cancer between 2005 and 2017. At 45.2%, nearly half of participants were privately insured.

Five models were created comparing the likelihood of being diagnosed with a more advance stage tumor (stage 3-4 vs. stage 1-2) between the most disadvantage quartile and the most advantaged group quartile. They found significant relationships for low versus high economic segregation for both the most disadvantaged quartile (odds ratio, 1.36; P < .05) and the second-most disadvantaged quartile (OR, 1.43; P < .05); low-income Black versus high-income White patients in both the most disadvantage quartile (OR, 1.55; P < .05) and the second-most disadvantaged quartile (OR, 1.44; P < .05); Hispanic versus non-Hispanic ethnicity in the most disadvantaged quartile (OR, 1.32; P < .05), and low-income Hispanics versus high-income Whites in both the most disadvantaged quartile (OR, 1.43; P < .05) and the second-most disadvantaged quartile (OR, 1.56; P < .05).

Black patients were more likely to be diagnosed with triple-negative breast cancer than White patients (25.1% vs. 12.5%; P < .001).

The findings suggest that both economically disadvantaged patients and those in racially or ethnically marginalized neighborhoods had a greater probability of having later-stage disease at diagnosis. The researchers controlled for age, insurance status, tumor subtype, and comorbidities like diabetes, coronary artery disease, and hyperlipidemia.

“This study adds insight to a growing body of literature that demonstrate how the ecological effects of structural racism – expressed through poverty and residential segregation – shape cancer outcomes across patients of all races [and] ethnicities,” Dr. Goel said.

Dr. Goel has no relevant financial disclosures.

A retrospective analysis of the National Cancer Database suggests an overall survival benefit to adjuvant chemotherapy among breast cancer patients with an OncotypeDX score of 25 or less. The findings reinforce the positive results from the RxPONDER study, which showed benefits to invasive disease–free and distant relapse–free survival.

OncotypeDX is a prognostic assay for hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative and axillary lymph-node–negative breast cancer. It measures expression of 21 different genes and assigns each patient a score between 0 and 100, with higher scores representing a greater risk of recurrence and a worse prognosis. The 2018 TAILORx study validated Oncotype DX and found no benefit of adjuvant chemotherapy added to endocrine therapy in women over 50 with an OncotypeDX score of 11-25, but it did find a benefit in women under 50 years old with a score of 16 or higher.

RxPONDER was a prospective study that randomized women with Oncotype DX scores of 25 or lower and 1-3 positive lymph nodes to adjuvant endocrine therapy with or without chemotherapy. Among premenopausal women, 5-year invasive disease–free survival was 93.9% with chemotherapy and 89.0% with endocrine therapy only (hazard ratio, 0.60; P = .002), while distant relapse–free survival was 96.1% and 92.8%, respectively (HR, 0.58; P = .009).

Overall survival data from RxPONDER has yet to be reported. In the meantime, “We decided to use the National Cancer database to see if this group of patients have an overall survival benefit,” said Prashanth Ashok Kumar, MBBS, who presented the results of the new study at a poster session this month during the 2022 San Antonio Breast Cancer Symposium.

“Our research further supports the findings of the RxPONDER trial showing that this subgroup of patients may also have an overall survival benefit with adjuvant chemotherapy. We can give physicians a little bit more confidence to recommend the findings of the RxPONDER study to their patients and could recommend chemotherapy in this group,” said Dr. Kumar, who is a second-year oncology fellow at Upstate University Hospital. Syracuse, N.Y.

The study is limited by its retrospective nature, but Dr. Kumar said that the researchers used propensity score matching to reduce confounding. “This would need to be confirmed with further prospective clinical trials and also the mature data from the RxPONDER trial is something that we have to look forward to,” he said.

Adjuvant therapy might be particularly beneficial to patients with more high-risk features, such as T4 or N2 or N3 disease. “We have to go with each individual patient’s features, and also the patient’s personal preference and what they want from their quality of life,” Dr. Kumar said.

The study included 8,628 patients from the 2004-2018 National Cancer Database participant user file. They were 18-50 years old with N1-N3 lymph node status, no metastasis, and any T stage. All had an OncotypeDX score of 25 or less and were hormone receptor–positive and HER2-negative while 40.8% underwent adjuvant chemotherapy.

Unadjusted Kaplan-Meier scores showed a slightly higher 10-year survival with adjuvant chemotherapy (93% versus 91%; HR, 0.602; 95% confidence interval, 0.482-0.751). Multivariate subanalyses showed that adjuvant chemotherapy was associated with better survival among White patients (HR, 0.512; 95% CI, 0.348-0.752) between 18 and 40 years old (HR, 0.429; 95% CI, 0.217-0.847), and for patients between 40 and 50 years old (HR, 0.585; 95% CI, 0.394-0.869); among patients with poorly differentiated tumors (HR, 0.404; 95% CI, 0.186-0.874); among patients with well-differentiated tumors (HR, 0.386; 95% CI, 0.165-0.903); and for those with Oncotype DX scores between 12 and 25 (HR, 0.549; 95% CI, 0.379-0.795).

Dr. Kumar has no relevant financial disclosures.

A retrospective analysis of the National Cancer Database suggests an overall survival benefit to adjuvant chemotherapy among breast cancer patients with an OncotypeDX score of 25 or less. The findings reinforce the positive results from the RxPONDER study, which showed benefits to invasive disease–free and distant relapse–free survival.

OncotypeDX is a prognostic assay for hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative and axillary lymph-node–negative breast cancer. It measures expression of 21 different genes and assigns each patient a score between 0 and 100, with higher scores representing a greater risk of recurrence and a worse prognosis. The 2018 TAILORx study validated Oncotype DX and found no benefit of adjuvant chemotherapy added to endocrine therapy in women over 50 with an OncotypeDX score of 11-25, but it did find a benefit in women under 50 years old with a score of 16 or higher.

RxPONDER was a prospective study that randomized women with Oncotype DX scores of 25 or lower and 1-3 positive lymph nodes to adjuvant endocrine therapy with or without chemotherapy. Among premenopausal women, 5-year invasive disease–free survival was 93.9% with chemotherapy and 89.0% with endocrine therapy only (hazard ratio, 0.60; P = .002), while distant relapse–free survival was 96.1% and 92.8%, respectively (HR, 0.58; P = .009).

Overall survival data from RxPONDER has yet to be reported. In the meantime, “We decided to use the National Cancer database to see if this group of patients have an overall survival benefit,” said Prashanth Ashok Kumar, MBBS, who presented the results of the new study at a poster session this month during the 2022 San Antonio Breast Cancer Symposium.

“Our research further supports the findings of the RxPONDER trial showing that this subgroup of patients may also have an overall survival benefit with adjuvant chemotherapy. We can give physicians a little bit more confidence to recommend the findings of the RxPONDER study to their patients and could recommend chemotherapy in this group,” said Dr. Kumar, who is a second-year oncology fellow at Upstate University Hospital. Syracuse, N.Y.

The study is limited by its retrospective nature, but Dr. Kumar said that the researchers used propensity score matching to reduce confounding. “This would need to be confirmed with further prospective clinical trials and also the mature data from the RxPONDER trial is something that we have to look forward to,” he said.

Adjuvant therapy might be particularly beneficial to patients with more high-risk features, such as T4 or N2 or N3 disease. “We have to go with each individual patient’s features, and also the patient’s personal preference and what they want from their quality of life,” Dr. Kumar said.

The study included 8,628 patients from the 2004-2018 National Cancer Database participant user file. They were 18-50 years old with N1-N3 lymph node status, no metastasis, and any T stage. All had an OncotypeDX score of 25 or less and were hormone receptor–positive and HER2-negative while 40.8% underwent adjuvant chemotherapy.

Unadjusted Kaplan-Meier scores showed a slightly higher 10-year survival with adjuvant chemotherapy (93% versus 91%; HR, 0.602; 95% confidence interval, 0.482-0.751). Multivariate subanalyses showed that adjuvant chemotherapy was associated with better survival among White patients (HR, 0.512; 95% CI, 0.348-0.752) between 18 and 40 years old (HR, 0.429; 95% CI, 0.217-0.847), and for patients between 40 and 50 years old (HR, 0.585; 95% CI, 0.394-0.869); among patients with poorly differentiated tumors (HR, 0.404; 95% CI, 0.186-0.874); among patients with well-differentiated tumors (HR, 0.386; 95% CI, 0.165-0.903); and for those with Oncotype DX scores between 12 and 25 (HR, 0.549; 95% CI, 0.379-0.795).

Dr. Kumar has no relevant financial disclosures.

A retrospective analysis of the National Cancer Database suggests an overall survival benefit to adjuvant chemotherapy among breast cancer patients with an OncotypeDX score of 25 or less. The findings reinforce the positive results from the RxPONDER study, which showed benefits to invasive disease–free and distant relapse–free survival.

OncotypeDX is a prognostic assay for hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative and axillary lymph-node–negative breast cancer. It measures expression of 21 different genes and assigns each patient a score between 0 and 100, with higher scores representing a greater risk of recurrence and a worse prognosis. The 2018 TAILORx study validated Oncotype DX and found no benefit of adjuvant chemotherapy added to endocrine therapy in women over 50 with an OncotypeDX score of 11-25, but it did find a benefit in women under 50 years old with a score of 16 or higher.

RxPONDER was a prospective study that randomized women with Oncotype DX scores of 25 or lower and 1-3 positive lymph nodes to adjuvant endocrine therapy with or without chemotherapy. Among premenopausal women, 5-year invasive disease–free survival was 93.9% with chemotherapy and 89.0% with endocrine therapy only (hazard ratio, 0.60; P = .002), while distant relapse–free survival was 96.1% and 92.8%, respectively (HR, 0.58; P = .009).

Overall survival data from RxPONDER has yet to be reported. In the meantime, “We decided to use the National Cancer database to see if this group of patients have an overall survival benefit,” said Prashanth Ashok Kumar, MBBS, who presented the results of the new study at a poster session this month during the 2022 San Antonio Breast Cancer Symposium.

“Our research further supports the findings of the RxPONDER trial showing that this subgroup of patients may also have an overall survival benefit with adjuvant chemotherapy. We can give physicians a little bit more confidence to recommend the findings of the RxPONDER study to their patients and could recommend chemotherapy in this group,” said Dr. Kumar, who is a second-year oncology fellow at Upstate University Hospital. Syracuse, N.Y.

The study is limited by its retrospective nature, but Dr. Kumar said that the researchers used propensity score matching to reduce confounding. “This would need to be confirmed with further prospective clinical trials and also the mature data from the RxPONDER trial is something that we have to look forward to,” he said.

Adjuvant therapy might be particularly beneficial to patients with more high-risk features, such as T4 or N2 or N3 disease. “We have to go with each individual patient’s features, and also the patient’s personal preference and what they want from their quality of life,” Dr. Kumar said.

The study included 8,628 patients from the 2004-2018 National Cancer Database participant user file. They were 18-50 years old with N1-N3 lymph node status, no metastasis, and any T stage. All had an OncotypeDX score of 25 or less and were hormone receptor–positive and HER2-negative while 40.8% underwent adjuvant chemotherapy.

Unadjusted Kaplan-Meier scores showed a slightly higher 10-year survival with adjuvant chemotherapy (93% versus 91%; HR, 0.602; 95% confidence interval, 0.482-0.751). Multivariate subanalyses showed that adjuvant chemotherapy was associated with better survival among White patients (HR, 0.512; 95% CI, 0.348-0.752) between 18 and 40 years old (HR, 0.429; 95% CI, 0.217-0.847), and for patients between 40 and 50 years old (HR, 0.585; 95% CI, 0.394-0.869); among patients with poorly differentiated tumors (HR, 0.404; 95% CI, 0.186-0.874); among patients with well-differentiated tumors (HR, 0.386; 95% CI, 0.165-0.903); and for those with Oncotype DX scores between 12 and 25 (HR, 0.549; 95% CI, 0.379-0.795).

Dr. Kumar has no relevant financial disclosures.

SAN ANTONIO – A wide range of research on hormone receptor (HR)–positive breast cancer was presented at the San Antonio Breast Cancer Symposium.

This news organization spoke with SABCS program director Virginia Kaklamani, MD, leader of the Breast Cancer Program at UT Health, San Antonio, and Jason A. Mouabbi, MD, of the University of Texas MD Anderson Cancer Center, Houston, about their top five picks on HR-positive disease – the research they were most excited about and what the findings could mean for clinical practice and patient outcomes.
 

1. Addressing an unmet need

Data from the phase 3 CAPItello-291 clinical trial showed that the addition of the investigational AKT inhibitor capivasertib to fulvestrant resulted in statistically significant and clinically meaningful improvement in progression-free survival (PFS) among 708 patients with HR-positive, HER2-negative advanced breast cancer, compared with those who received placebo plus fulvestrant (GS3-04).

For patients treated with capivasertib plus fulvestrant, median PFS was 7.2 months, compared with 3.6 months for those who received placebo plus fulvestrant (hazard ratio, 0.60). Among patients assigned to the capivasertib group, 41% had tumors with AKT pathway mutations. In this group, the median PFS was 7.3 months vs. 3.1 months in the placebo cohort. The objective response rate among patients with measurable disease was 23% overall in the capivasertib group, compared with 12.2% in the placebo arm; it was 28.8% vs. 9.7% among the patients with AKT alterations.

Dr. Mouabbi noted that the study “met its primary endpoint” and that, importantly, it “addresses an area of unmet need.”

“The study’s treatment targets the PI3K/AKT/mTOR pathway, which is a very active pathway in hormone-positive metastatic breast cancer,” Dr. Mouabbi explained. He noted, “We’ve always wanted to tackle that pathway effectively, and it looks like this drug can do that.”
 

2. Next-generation SERD

Data from the phase 2 SERENA-2 trial offers evidence that camizestrant, a next-generation selective estrogen-receptor degrader (SERD), improved PFS compared with fulvestrant for patients with HR-positive, HER2-negative breast cancer (GS3-02).

Overall, 240 patients were randomly assigned to receive camizestrant monotherapy at various doses or fulvestrant at 500 mg. Among patients who received camizestrant 75 mg, median PFS was 7.2 months; among those who received camizestrant 150 mg, PFS was slightly longer, at 7.7 months vs. 3.7 months for patients treated with fulvestrant. Compared with fulvestrant, camizestrant reduced the risk of disease progression by 42% at 75 mg (HR, 0.58) and by 33% at 150 mg (HR, 0.67). In a subgroup of patients with ESR1 mutations, camizestrant reduced the risk of disease progression by 67% in the group that received 75 mg and by 45% in the group that received 150 mg, compared with fulvestrant (median PFS, 6.3, 9.2, and 2.2 months, respectively).

“In this trial, camizestrant looks like a more beneficial treatment in the target group,” said Dr. Kaklamani. “This is significant because it means that camizestrant could be used in the future in HR-positive metastatic breast cancer instead of fulvestrant.” In addition, “camizestrant is taken orally and is much more convenient for patients, unlike fulvestrant, which is taken intramuscularly.”
 

3. Pregnancy risks

Can endocrine therapy be safely interrupted for women with breast cancer who wish to become pregnant? That’s what researchers tried to glean in a recent prospective trial presented at the meeting (GS4-09).

The study enrolled over 500 women for whom endocrine therapy had been stopped in the hopes of their becoming pregnant. Almost all (93.4%) had stage I/II HR-positive breast cancer. The primary objective was to determine the risk of breast cancer relapse associated with interrupting therapy for about 2 years. The authors defined no more than 46 breast cancer–free interval (BCFI) events as the safety threshold. A BCFI event was defined as local, regional, or distant recurrence or a new invasive contralateral breast cancer.

Among 497 women, 368 (74%) had at least one pregnancy and 317 (64%) had at least one live birth, for a total of 365 babies born. At a median follow-up of 41 months, 44 participants experienced a BCFI event, in line with the safety threshold. The 3-year BCFI failure rate was 8.9%, similar to the 9.2% rate in an external control cohort from the SOFT/TEXT trials. In addition, 76.3% of patients resumed endocrine therapy; 15.4% had not yet resumed therapy.

“This trial is more confirmatory but an extremely important step for young women who want to get pregnant after diagnosis and recovery from HR-positive breast cancer,” Dr. Kaklamani said. “It seems that stopping endocrine therapy to become pregnant did not cause any adverse outcomes or increase the risk of reoccurrence of cancer in the women in the study.”

Dr. Mouabbi agreed, noting, “Many of our patients are afraid that they will miss the window to get pregnant because they have to be on treatment for so long. This is the first study that let us know pregnancy and safety outcomes in patients who took a break from endocrine therapy to get pregnant. The results are promising and will be exciting for many of our patients.”
 

4. Assay identifies OFS benefit

A genomic assay was able to distinguish premenopausal patients with early-stage HR-positive breast cancer who benefited from the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy, according to new data presented at the meeting (GS1-06).

In the study, investigators analyzed 1,717 patient tumor samples from the landmark Suppression of Ovarian Function Trial (SOFT) trial. The Breast Cancer Index identified 58% of women who benefited from the addition of ovarian function suppression to tamoxifen or exemestane therapy. They experienced an absolute benefit of 11.6% (42% did not benefit), compared with those with received tamoxifen alone. The predictive benefit was observed regardless of age, lymph node involvement, and receipt of chemotherapy.

Dr. Kaklamani highlighted this study’s importance, saying, “Ovarian suppression is associated with severe adverse events for patients. Obviously, the women who will get a benefit should continue, but this research is important because it will hopefully show us who to recommend ovarian suppression to while not exposing patients who are likely to get little benefit to unneeded toxicity.”
 

5. Optimizing elacestrant PFS

Last year, data from the Emerald trial showed that elacestrant is superior to standard-of-care therapy for HR-positive metastatic breast cancer. An update that Dr. Kaklamani presented at SABCS (GS3-01) explored whether the duration of a prior CDK4/6 inhibitor affects PFS.

The study was a randomized, open-label, phase 3 trial in which 478 patients with ER-positive/HER2-negative metastatic breast cancer received either elacestrant or standard of care. These patients had previously received one or two lines of endocrine therapy, a CDK4/6 inhibitor, and ≤ 1 line of chemotherapy.

Overall, the duration of prior CDK4/6 inhibitor in the metastatic setting was positively associated with PFS – the longer the duration of prior CDK4/6 inhibitor therapy, the longer the PFS with elacestrant. PFS outcomes were even stronger among patients with ESR1 mutations.

“What we found was that the women who benefit most from elacestrant had previously received a CDK4/6 inhibitor for at least 6 months,” Dr. Kaklamani said. These data can help us determine who may do best on the drug, she added.

A version of this article first appeared on Medscape.com.

SAN ANTONIO – A wide range of research on hormone receptor (HR)–positive breast cancer was presented at the San Antonio Breast Cancer Symposium.

This news organization spoke with SABCS program director Virginia Kaklamani, MD, leader of the Breast Cancer Program at UT Health, San Antonio, and Jason A. Mouabbi, MD, of the University of Texas MD Anderson Cancer Center, Houston, about their top five picks on HR-positive disease – the research they were most excited about and what the findings could mean for clinical practice and patient outcomes.
 

1. Addressing an unmet need

Data from the phase 3 CAPItello-291 clinical trial showed that the addition of the investigational AKT inhibitor capivasertib to fulvestrant resulted in statistically significant and clinically meaningful improvement in progression-free survival (PFS) among 708 patients with HR-positive, HER2-negative advanced breast cancer, compared with those who received placebo plus fulvestrant (GS3-04).

For patients treated with capivasertib plus fulvestrant, median PFS was 7.2 months, compared with 3.6 months for those who received placebo plus fulvestrant (hazard ratio, 0.60). Among patients assigned to the capivasertib group, 41% had tumors with AKT pathway mutations. In this group, the median PFS was 7.3 months vs. 3.1 months in the placebo cohort. The objective response rate among patients with measurable disease was 23% overall in the capivasertib group, compared with 12.2% in the placebo arm; it was 28.8% vs. 9.7% among the patients with AKT alterations.

Dr. Mouabbi noted that the study “met its primary endpoint” and that, importantly, it “addresses an area of unmet need.”

“The study’s treatment targets the PI3K/AKT/mTOR pathway, which is a very active pathway in hormone-positive metastatic breast cancer,” Dr. Mouabbi explained. He noted, “We’ve always wanted to tackle that pathway effectively, and it looks like this drug can do that.”
 

2. Next-generation SERD

Data from the phase 2 SERENA-2 trial offers evidence that camizestrant, a next-generation selective estrogen-receptor degrader (SERD), improved PFS compared with fulvestrant for patients with HR-positive, HER2-negative breast cancer (GS3-02).

Overall, 240 patients were randomly assigned to receive camizestrant monotherapy at various doses or fulvestrant at 500 mg. Among patients who received camizestrant 75 mg, median PFS was 7.2 months; among those who received camizestrant 150 mg, PFS was slightly longer, at 7.7 months vs. 3.7 months for patients treated with fulvestrant. Compared with fulvestrant, camizestrant reduced the risk of disease progression by 42% at 75 mg (HR, 0.58) and by 33% at 150 mg (HR, 0.67). In a subgroup of patients with ESR1 mutations, camizestrant reduced the risk of disease progression by 67% in the group that received 75 mg and by 45% in the group that received 150 mg, compared with fulvestrant (median PFS, 6.3, 9.2, and 2.2 months, respectively).

“In this trial, camizestrant looks like a more beneficial treatment in the target group,” said Dr. Kaklamani. “This is significant because it means that camizestrant could be used in the future in HR-positive metastatic breast cancer instead of fulvestrant.” In addition, “camizestrant is taken orally and is much more convenient for patients, unlike fulvestrant, which is taken intramuscularly.”
 

3. Pregnancy risks

Can endocrine therapy be safely interrupted for women with breast cancer who wish to become pregnant? That’s what researchers tried to glean in a recent prospective trial presented at the meeting (GS4-09).

The study enrolled over 500 women for whom endocrine therapy had been stopped in the hopes of their becoming pregnant. Almost all (93.4%) had stage I/II HR-positive breast cancer. The primary objective was to determine the risk of breast cancer relapse associated with interrupting therapy for about 2 years. The authors defined no more than 46 breast cancer–free interval (BCFI) events as the safety threshold. A BCFI event was defined as local, regional, or distant recurrence or a new invasive contralateral breast cancer.

Among 497 women, 368 (74%) had at least one pregnancy and 317 (64%) had at least one live birth, for a total of 365 babies born. At a median follow-up of 41 months, 44 participants experienced a BCFI event, in line with the safety threshold. The 3-year BCFI failure rate was 8.9%, similar to the 9.2% rate in an external control cohort from the SOFT/TEXT trials. In addition, 76.3% of patients resumed endocrine therapy; 15.4% had not yet resumed therapy.

“This trial is more confirmatory but an extremely important step for young women who want to get pregnant after diagnosis and recovery from HR-positive breast cancer,” Dr. Kaklamani said. “It seems that stopping endocrine therapy to become pregnant did not cause any adverse outcomes or increase the risk of reoccurrence of cancer in the women in the study.”

Dr. Mouabbi agreed, noting, “Many of our patients are afraid that they will miss the window to get pregnant because they have to be on treatment for so long. This is the first study that let us know pregnancy and safety outcomes in patients who took a break from endocrine therapy to get pregnant. The results are promising and will be exciting for many of our patients.”
 

4. Assay identifies OFS benefit

A genomic assay was able to distinguish premenopausal patients with early-stage HR-positive breast cancer who benefited from the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy, according to new data presented at the meeting (GS1-06).

In the study, investigators analyzed 1,717 patient tumor samples from the landmark Suppression of Ovarian Function Trial (SOFT) trial. The Breast Cancer Index identified 58% of women who benefited from the addition of ovarian function suppression to tamoxifen or exemestane therapy. They experienced an absolute benefit of 11.6% (42% did not benefit), compared with those with received tamoxifen alone. The predictive benefit was observed regardless of age, lymph node involvement, and receipt of chemotherapy.

Dr. Kaklamani highlighted this study’s importance, saying, “Ovarian suppression is associated with severe adverse events for patients. Obviously, the women who will get a benefit should continue, but this research is important because it will hopefully show us who to recommend ovarian suppression to while not exposing patients who are likely to get little benefit to unneeded toxicity.”
 

5. Optimizing elacestrant PFS

Last year, data from the Emerald trial showed that elacestrant is superior to standard-of-care therapy for HR-positive metastatic breast cancer. An update that Dr. Kaklamani presented at SABCS (GS3-01) explored whether the duration of a prior CDK4/6 inhibitor affects PFS.

The study was a randomized, open-label, phase 3 trial in which 478 patients with ER-positive/HER2-negative metastatic breast cancer received either elacestrant or standard of care. These patients had previously received one or two lines of endocrine therapy, a CDK4/6 inhibitor, and ≤ 1 line of chemotherapy.

Overall, the duration of prior CDK4/6 inhibitor in the metastatic setting was positively associated with PFS – the longer the duration of prior CDK4/6 inhibitor therapy, the longer the PFS with elacestrant. PFS outcomes were even stronger among patients with ESR1 mutations.

“What we found was that the women who benefit most from elacestrant had previously received a CDK4/6 inhibitor for at least 6 months,” Dr. Kaklamani said. These data can help us determine who may do best on the drug, she added.

A version of this article first appeared on Medscape.com.

SAN ANTONIO – A wide range of research on hormone receptor (HR)–positive breast cancer was presented at the San Antonio Breast Cancer Symposium.

This news organization spoke with SABCS program director Virginia Kaklamani, MD, leader of the Breast Cancer Program at UT Health, San Antonio, and Jason A. Mouabbi, MD, of the University of Texas MD Anderson Cancer Center, Houston, about their top five picks on HR-positive disease – the research they were most excited about and what the findings could mean for clinical practice and patient outcomes.
 

1. Addressing an unmet need

Data from the phase 3 CAPItello-291 clinical trial showed that the addition of the investigational AKT inhibitor capivasertib to fulvestrant resulted in statistically significant and clinically meaningful improvement in progression-free survival (PFS) among 708 patients with HR-positive, HER2-negative advanced breast cancer, compared with those who received placebo plus fulvestrant (GS3-04).

For patients treated with capivasertib plus fulvestrant, median PFS was 7.2 months, compared with 3.6 months for those who received placebo plus fulvestrant (hazard ratio, 0.60). Among patients assigned to the capivasertib group, 41% had tumors with AKT pathway mutations. In this group, the median PFS was 7.3 months vs. 3.1 months in the placebo cohort. The objective response rate among patients with measurable disease was 23% overall in the capivasertib group, compared with 12.2% in the placebo arm; it was 28.8% vs. 9.7% among the patients with AKT alterations.

Dr. Mouabbi noted that the study “met its primary endpoint” and that, importantly, it “addresses an area of unmet need.”

“The study’s treatment targets the PI3K/AKT/mTOR pathway, which is a very active pathway in hormone-positive metastatic breast cancer,” Dr. Mouabbi explained. He noted, “We’ve always wanted to tackle that pathway effectively, and it looks like this drug can do that.”
 

2. Next-generation SERD

Data from the phase 2 SERENA-2 trial offers evidence that camizestrant, a next-generation selective estrogen-receptor degrader (SERD), improved PFS compared with fulvestrant for patients with HR-positive, HER2-negative breast cancer (GS3-02).

Overall, 240 patients were randomly assigned to receive camizestrant monotherapy at various doses or fulvestrant at 500 mg. Among patients who received camizestrant 75 mg, median PFS was 7.2 months; among those who received camizestrant 150 mg, PFS was slightly longer, at 7.7 months vs. 3.7 months for patients treated with fulvestrant. Compared with fulvestrant, camizestrant reduced the risk of disease progression by 42% at 75 mg (HR, 0.58) and by 33% at 150 mg (HR, 0.67). In a subgroup of patients with ESR1 mutations, camizestrant reduced the risk of disease progression by 67% in the group that received 75 mg and by 45% in the group that received 150 mg, compared with fulvestrant (median PFS, 6.3, 9.2, and 2.2 months, respectively).

“In this trial, camizestrant looks like a more beneficial treatment in the target group,” said Dr. Kaklamani. “This is significant because it means that camizestrant could be used in the future in HR-positive metastatic breast cancer instead of fulvestrant.” In addition, “camizestrant is taken orally and is much more convenient for patients, unlike fulvestrant, which is taken intramuscularly.”
 

3. Pregnancy risks

Can endocrine therapy be safely interrupted for women with breast cancer who wish to become pregnant? That’s what researchers tried to glean in a recent prospective trial presented at the meeting (GS4-09).

The study enrolled over 500 women for whom endocrine therapy had been stopped in the hopes of their becoming pregnant. Almost all (93.4%) had stage I/II HR-positive breast cancer. The primary objective was to determine the risk of breast cancer relapse associated with interrupting therapy for about 2 years. The authors defined no more than 46 breast cancer–free interval (BCFI) events as the safety threshold. A BCFI event was defined as local, regional, or distant recurrence or a new invasive contralateral breast cancer.

Among 497 women, 368 (74%) had at least one pregnancy and 317 (64%) had at least one live birth, for a total of 365 babies born. At a median follow-up of 41 months, 44 participants experienced a BCFI event, in line with the safety threshold. The 3-year BCFI failure rate was 8.9%, similar to the 9.2% rate in an external control cohort from the SOFT/TEXT trials. In addition, 76.3% of patients resumed endocrine therapy; 15.4% had not yet resumed therapy.

“This trial is more confirmatory but an extremely important step for young women who want to get pregnant after diagnosis and recovery from HR-positive breast cancer,” Dr. Kaklamani said. “It seems that stopping endocrine therapy to become pregnant did not cause any adverse outcomes or increase the risk of reoccurrence of cancer in the women in the study.”

Dr. Mouabbi agreed, noting, “Many of our patients are afraid that they will miss the window to get pregnant because they have to be on treatment for so long. This is the first study that let us know pregnancy and safety outcomes in patients who took a break from endocrine therapy to get pregnant. The results are promising and will be exciting for many of our patients.”
 

4. Assay identifies OFS benefit

A genomic assay was able to distinguish premenopausal patients with early-stage HR-positive breast cancer who benefited from the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy, according to new data presented at the meeting (GS1-06).

In the study, investigators analyzed 1,717 patient tumor samples from the landmark Suppression of Ovarian Function Trial (SOFT) trial. The Breast Cancer Index identified 58% of women who benefited from the addition of ovarian function suppression to tamoxifen or exemestane therapy. They experienced an absolute benefit of 11.6% (42% did not benefit), compared with those with received tamoxifen alone. The predictive benefit was observed regardless of age, lymph node involvement, and receipt of chemotherapy.

Dr. Kaklamani highlighted this study’s importance, saying, “Ovarian suppression is associated with severe adverse events for patients. Obviously, the women who will get a benefit should continue, but this research is important because it will hopefully show us who to recommend ovarian suppression to while not exposing patients who are likely to get little benefit to unneeded toxicity.”
 

5. Optimizing elacestrant PFS

Last year, data from the Emerald trial showed that elacestrant is superior to standard-of-care therapy for HR-positive metastatic breast cancer. An update that Dr. Kaklamani presented at SABCS (GS3-01) explored whether the duration of a prior CDK4/6 inhibitor affects PFS.

The study was a randomized, open-label, phase 3 trial in which 478 patients with ER-positive/HER2-negative metastatic breast cancer received either elacestrant or standard of care. These patients had previously received one or two lines of endocrine therapy, a CDK4/6 inhibitor, and ≤ 1 line of chemotherapy.

Overall, the duration of prior CDK4/6 inhibitor in the metastatic setting was positively associated with PFS – the longer the duration of prior CDK4/6 inhibitor therapy, the longer the PFS with elacestrant. PFS outcomes were even stronger among patients with ESR1 mutations.

“What we found was that the women who benefit most from elacestrant had previously received a CDK4/6 inhibitor for at least 6 months,” Dr. Kaklamani said. These data can help us determine who may do best on the drug, she added.

A version of this article first appeared on Medscape.com.

SAN ANTONIO – Women with breast cancer at more than one site can undergo breast-conserving therapy and still have local recurrence rates well under the acceptable threshold of risk, suggest the results of first prospective study of this issue.

The ACOSOG-Z11102 trial involved more than 200 women with primarily endocrine receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer and up to three disease foci, all of whom underwent lumpectomy with nodal staging followed by whole-breast irradiation, then systemic therapy at the oncologist’s discretion.

After 5 years of follow-up, just 3% of women experienced a local recurrence, with none having a local or distant recurrence and one dying of the disease.

Although the numbers were small, the data indicated that preoperative MRI to evaluate disease extent, and adjuvant endocrine therapy in women with ER+ disease, were associated with lower recurrence rates.

The new findings were presented at the San Antonio Breast Cancer Symposium on Dec. 9.

“This study provides important information for clinicians to discuss with patients who have two or three foci of breast cancer in one breast, as it may allow more patients to consider breast-conserving therapy as an option,” said study presenter Judy C. Boughey, MD, chair of the division of breast and melanoma surgical oncology at the Mayo Clinic, Rochester, Minn.

“Lumpectomy with radiation therapy is often preferred to mastectomy, as it is a smaller operation with quicker recovery, resulting in better patient satisfaction and cosmetic outcomes,” Dr. Boughey said in a statement.

“We’ve all been anxiously awaiting the results of this trial,” Andrea V. Barrio, MD, associate attending surgeon, Memorial Sloan Kettering Cancer Center, New York, told this news organization. “We knew that in patients who have a single site tumor in the breast, that outcomes between lumpectomy and mastectomy are the same ... But none of those trials have enrolled women with multiple sites.”

“There were no prospective data out there telling us that doing two lumpectomies in the breast was safe, so a lot of times, women were getting mastectomy for these multiple tumors, even if women had two small tumors in the breast and could easily undergo a lumpectomy with a good cosmetic result,” she said.

“So this data provides very strong evidence that we can begin treating women with small tumors in the breast who can undergo lumpectomy with a good cosmetic results without needing a mastectomy,” Dr. Barrio continued. “From a long-term quality of life standpoint, this is a big deal for women moving forward who really want to keep their breasts.”

Dr. Barrio did highlight, however, that “not everybody routinely does MRI” in women with breast cancer, including her institution, although generally she feels that “our standard imaging has gotten better,” with screening ultrasound identifying more lesions than previously.

She also believes that the numbers of women in the study who did not receive MRI are too small to “draw any definitive conclusions.

“Personally, when I have a patient with multisite disease and I’m going to keep their breasts, that to me is one indication that I would consider an MRI, to make sure that I wasn’t missing intervening disease between the two sites – that there wasn’t something else that would change my mind about doing a two-site lumpectomy,” Dr. Barrio said.

Linda M. Pak, MD, a breast cancer surgeon and surgical oncologist at NYU Langone’s Breast Cancer Center, New York, who was not involved in the study, said that the new study provides “importation information regarding the oncologic safety” of lumpectomy.

These results are “exciting to see, as they provide important information that breast-conserving surgery is safe in these patients, and that we can now share the results of this study with patients when we discuss with them their surgical options.

“I hope this will make more breast surgeons and patients comfortable with this approach and that it will increase the use of breast conservation among these patients,” Dr. Pak said.
 

Study details

In recent years, there has been increased diagnosis of multiple foci of ipsilateral breast cancer, Dr. Boughey said in her presentation. “This is both as a result of improvements in screening imaging, as well as diagnostic imaging and an increased use of preoperative breast MRI.”

Although historical, retrospective studies have shown high rates of local regional recurrences with breast-conserving therapy in women with more than one foci of breast cancer, more recent analyses have indicated that the approach is associated with “acceptable” recurrence rates.

This, Dr. Boughey explained, is due not only to improvements in breast imaging but also to better pathologic margin assessment, and improved systematic and radiation therapy.

Nevertheless, “most patients who present with two or three sites of cancer in one breast are recommended to undergo a mastectomy,” she noted.

To examine the safety of breast-conserving therapy in such patients, the team conducted a single-arm, phase 2 trial in women at least 40 years of age who had two or three foci of breast cancer, of which at least one site was invasive disease.

“While a randomized trial design would have provided stronger data, we felt that accrual to such a design would be problematic, as many patients and surgeons would not be willing to randomize,” Dr. Boughey explained.

Participants were required to have at least 2 cm of normal tissue between the lesions and disease in no more than two quadrants of the breast. They could have node-negative or N1 disease.

Women were excluded if they had foci > 5 cm on imaging; had bilateral breast cancer; had known BRCA1/2 mutations; had had prior ipsilateral breast cancer; or had received neoadjuvant therapy.

All women in the trial underwent lumpectomy with nodal staging, with adjuvant chemotherapy at the physician’s discretion, followed by whole-breast irradiation, with regional nodal irradiation again at the physician’s discretion. This was followed by systemic therapy, at the discretion of the medical oncologist.

The women were then followed up every 6 months until 5 years after the completion of whole-breast irradiation.
 

Details of the results

Dr. Boughey said that previously presented data from this study revealed that 67.6% of women achieved a margin-negative excision in a single operation, whereas 7.1% converted to mastectomy. The cosmetic outcome was rated as good or excellent at 2 years by 70.6% of women.

For the current analysis, a total of 204 women were evaluable, who had a median age of 61.1 years. Just over half (59.3%) had T1 stage disease, and 95.6% were node-negative. The majority (83.5%) had ER+/HER2- breast cancer, whereas 5.0% had ER-/HER2- disease and 11.5% had HER2+ positive tumors.

Adjuvant chemotherapy was given to 28.9% of women, whereas 89.7% of those with ER+ disease received adjuvant endocrine therapy.

The primary outcome was local recurrence rate at 5 years, which had a prespecified acceptable rate of less than 8%.

Dr. Boughey showed that, in their series, the 5-year recurrence rate was just 3.1% (95% confidence interval [CI], 1.3%-6.4%), which was “well below” the predefined “clinically significantly threshold.” This involved four cases in the ipsilateral breast, one in the skin, and one in the chest wall.

In addition to the six women with local regional recurrence, six developed contralateral breast cancer and four patients developed distant disease. There were no cases of local and distant recurrence. There were three non–breast cancer primary cancers: one gastric, one lung, and one ovarian.

Eight women died during follow-up; only one of the deaths was related to breast cancer.

Dr. Boughey explained that the small number of local recurrences was too small to identify predictive factors via multivariate analysis.

However, univariate analysis indicated that there were numerical but nonsignificant associations between local recurrence and pathologic stage T2-3 disease, pathologic nodal involvement, and surgical margins just under the negative threshold.

Among the 10 cases of ER–/HER2– breast cancer, there was one local recurrence, giving a 5-year rate of 10.0% vs. 2.6% for women with ER+/HER2– disease.

To examine the role of MRI, Dr. Boughey highlighted that although the imaging modality was initially a requirement for study entry, an amendment to the protocol in 2015 allowed 15 women who had not had MRI to take part.

The local recurrence rate in women who had undergone MRI was 1.7% vs. 22.6% in those who had not, for a hazard ratio of 13.5 (P = .002).

“While this was statistically significant, we need to bear in mind that this was a secondary unplanned analysis,” Dr. Boughey underlined.

Next, the team analyzed the impact of adjuvant endocrine therapy in the 195 women with at least one ER+ lesion, finding that it was associated with a 5-year recurrence rate of 1.9% vs. 12.5% in those who did not receive endocrine therapy, for a hazard ratio of 7.7 (P = .025).

Dr. Boughey highlighted that the study is limited by being single-arm and having only a small subset of patients without preoperative MRI, with HER2+ or ER–/HER2– disease, and with three foci of disease.

She also emphasized that “there is concern that the 5-year follow up on this protocol may be shorter than needed,” especially in women with ER+ disease.

The study was supported by the National Institutes of Health. Dr. Boughey declared relationships with Eli Lilly and Company, Symbiosis Pharma, CairnSurgical, UpToDate, and PeerView.

A version of this article first appeared on Medscape.com.

SAN ANTONIO – Women with breast cancer at more than one site can undergo breast-conserving therapy and still have local recurrence rates well under the acceptable threshold of risk, suggest the results of first prospective study of this issue.

The ACOSOG-Z11102 trial involved more than 200 women with primarily endocrine receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer and up to three disease foci, all of whom underwent lumpectomy with nodal staging followed by whole-breast irradiation, then systemic therapy at the oncologist’s discretion.

After 5 years of follow-up, just 3% of women experienced a local recurrence, with none having a local or distant recurrence and one dying of the disease.

Although the numbers were small, the data indicated that preoperative MRI to evaluate disease extent, and adjuvant endocrine therapy in women with ER+ disease, were associated with lower recurrence rates.

The new findings were presented at the San Antonio Breast Cancer Symposium on Dec. 9.

“This study provides important information for clinicians to discuss with patients who have two or three foci of breast cancer in one breast, as it may allow more patients to consider breast-conserving therapy as an option,” said study presenter Judy C. Boughey, MD, chair of the division of breast and melanoma surgical oncology at the Mayo Clinic, Rochester, Minn.

“Lumpectomy with radiation therapy is often preferred to mastectomy, as it is a smaller operation with quicker recovery, resulting in better patient satisfaction and cosmetic outcomes,” Dr. Boughey said in a statement.

“We’ve all been anxiously awaiting the results of this trial,” Andrea V. Barrio, MD, associate attending surgeon, Memorial Sloan Kettering Cancer Center, New York, told this news organization. “We knew that in patients who have a single site tumor in the breast, that outcomes between lumpectomy and mastectomy are the same ... But none of those trials have enrolled women with multiple sites.”

“There were no prospective data out there telling us that doing two lumpectomies in the breast was safe, so a lot of times, women were getting mastectomy for these multiple tumors, even if women had two small tumors in the breast and could easily undergo a lumpectomy with a good cosmetic result,” she said.

“So this data provides very strong evidence that we can begin treating women with small tumors in the breast who can undergo lumpectomy with a good cosmetic results without needing a mastectomy,” Dr. Barrio continued. “From a long-term quality of life standpoint, this is a big deal for women moving forward who really want to keep their breasts.”

Dr. Barrio did highlight, however, that “not everybody routinely does MRI” in women with breast cancer, including her institution, although generally she feels that “our standard imaging has gotten better,” with screening ultrasound identifying more lesions than previously.

She also believes that the numbers of women in the study who did not receive MRI are too small to “draw any definitive conclusions.

“Personally, when I have a patient with multisite disease and I’m going to keep their breasts, that to me is one indication that I would consider an MRI, to make sure that I wasn’t missing intervening disease between the two sites – that there wasn’t something else that would change my mind about doing a two-site lumpectomy,” Dr. Barrio said.

Linda M. Pak, MD, a breast cancer surgeon and surgical oncologist at NYU Langone’s Breast Cancer Center, New York, who was not involved in the study, said that the new study provides “importation information regarding the oncologic safety” of lumpectomy.

These results are “exciting to see, as they provide important information that breast-conserving surgery is safe in these patients, and that we can now share the results of this study with patients when we discuss with them their surgical options.

“I hope this will make more breast surgeons and patients comfortable with this approach and that it will increase the use of breast conservation among these patients,” Dr. Pak said.
 

Study details

In recent years, there has been increased diagnosis of multiple foci of ipsilateral breast cancer, Dr. Boughey said in her presentation. “This is both as a result of improvements in screening imaging, as well as diagnostic imaging and an increased use of preoperative breast MRI.”

Although historical, retrospective studies have shown high rates of local regional recurrences with breast-conserving therapy in women with more than one foci of breast cancer, more recent analyses have indicated that the approach is associated with “acceptable” recurrence rates.

This, Dr. Boughey explained, is due not only to improvements in breast imaging but also to better pathologic margin assessment, and improved systematic and radiation therapy.

Nevertheless, “most patients who present with two or three sites of cancer in one breast are recommended to undergo a mastectomy,” she noted.

To examine the safety of breast-conserving therapy in such patients, the team conducted a single-arm, phase 2 trial in women at least 40 years of age who had two or three foci of breast cancer, of which at least one site was invasive disease.

“While a randomized trial design would have provided stronger data, we felt that accrual to such a design would be problematic, as many patients and surgeons would not be willing to randomize,” Dr. Boughey explained.

Participants were required to have at least 2 cm of normal tissue between the lesions and disease in no more than two quadrants of the breast. They could have node-negative or N1 disease.

Women were excluded if they had foci > 5 cm on imaging; had bilateral breast cancer; had known BRCA1/2 mutations; had had prior ipsilateral breast cancer; or had received neoadjuvant therapy.

All women in the trial underwent lumpectomy with nodal staging, with adjuvant chemotherapy at the physician’s discretion, followed by whole-breast irradiation, with regional nodal irradiation again at the physician’s discretion. This was followed by systemic therapy, at the discretion of the medical oncologist.

The women were then followed up every 6 months until 5 years after the completion of whole-breast irradiation.
 

Details of the results

Dr. Boughey said that previously presented data from this study revealed that 67.6% of women achieved a margin-negative excision in a single operation, whereas 7.1% converted to mastectomy. The cosmetic outcome was rated as good or excellent at 2 years by 70.6% of women.

For the current analysis, a total of 204 women were evaluable, who had a median age of 61.1 years. Just over half (59.3%) had T1 stage disease, and 95.6% were node-negative. The majority (83.5%) had ER+/HER2- breast cancer, whereas 5.0% had ER-/HER2- disease and 11.5% had HER2+ positive tumors.

Adjuvant chemotherapy was given to 28.9% of women, whereas 89.7% of those with ER+ disease received adjuvant endocrine therapy.

The primary outcome was local recurrence rate at 5 years, which had a prespecified acceptable rate of less than 8%.

Dr. Boughey showed that, in their series, the 5-year recurrence rate was just 3.1% (95% confidence interval [CI], 1.3%-6.4%), which was “well below” the predefined “clinically significantly threshold.” This involved four cases in the ipsilateral breast, one in the skin, and one in the chest wall.

In addition to the six women with local regional recurrence, six developed contralateral breast cancer and four patients developed distant disease. There were no cases of local and distant recurrence. There were three non–breast cancer primary cancers: one gastric, one lung, and one ovarian.

Eight women died during follow-up; only one of the deaths was related to breast cancer.

Dr. Boughey explained that the small number of local recurrences was too small to identify predictive factors via multivariate analysis.

However, univariate analysis indicated that there were numerical but nonsignificant associations between local recurrence and pathologic stage T2-3 disease, pathologic nodal involvement, and surgical margins just under the negative threshold.

Among the 10 cases of ER–/HER2– breast cancer, there was one local recurrence, giving a 5-year rate of 10.0% vs. 2.6% for women with ER+/HER2– disease.

To examine the role of MRI, Dr. Boughey highlighted that although the imaging modality was initially a requirement for study entry, an amendment to the protocol in 2015 allowed 15 women who had not had MRI to take part.

The local recurrence rate in women who had undergone MRI was 1.7% vs. 22.6% in those who had not, for a hazard ratio of 13.5 (P = .002).

“While this was statistically significant, we need to bear in mind that this was a secondary unplanned analysis,” Dr. Boughey underlined.

Next, the team analyzed the impact of adjuvant endocrine therapy in the 195 women with at least one ER+ lesion, finding that it was associated with a 5-year recurrence rate of 1.9% vs. 12.5% in those who did not receive endocrine therapy, for a hazard ratio of 7.7 (P = .025).

Dr. Boughey highlighted that the study is limited by being single-arm and having only a small subset of patients without preoperative MRI, with HER2+ or ER–/HER2– disease, and with three foci of disease.

She also emphasized that “there is concern that the 5-year follow up on this protocol may be shorter than needed,” especially in women with ER+ disease.

The study was supported by the National Institutes of Health. Dr. Boughey declared relationships with Eli Lilly and Company, Symbiosis Pharma, CairnSurgical, UpToDate, and PeerView.

A version of this article first appeared on Medscape.com.

SAN ANTONIO – Women with breast cancer at more than one site can undergo breast-conserving therapy and still have local recurrence rates well under the acceptable threshold of risk, suggest the results of first prospective study of this issue.

The ACOSOG-Z11102 trial involved more than 200 women with primarily endocrine receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer and up to three disease foci, all of whom underwent lumpectomy with nodal staging followed by whole-breast irradiation, then systemic therapy at the oncologist’s discretion.

After 5 years of follow-up, just 3% of women experienced a local recurrence, with none having a local or distant recurrence and one dying of the disease.

Although the numbers were small, the data indicated that preoperative MRI to evaluate disease extent, and adjuvant endocrine therapy in women with ER+ disease, were associated with lower recurrence rates.

The new findings were presented at the San Antonio Breast Cancer Symposium on Dec. 9.

“This study provides important information for clinicians to discuss with patients who have two or three foci of breast cancer in one breast, as it may allow more patients to consider breast-conserving therapy as an option,” said study presenter Judy C. Boughey, MD, chair of the division of breast and melanoma surgical oncology at the Mayo Clinic, Rochester, Minn.

“Lumpectomy with radiation therapy is often preferred to mastectomy, as it is a smaller operation with quicker recovery, resulting in better patient satisfaction and cosmetic outcomes,” Dr. Boughey said in a statement.

“We’ve all been anxiously awaiting the results of this trial,” Andrea V. Barrio, MD, associate attending surgeon, Memorial Sloan Kettering Cancer Center, New York, told this news organization. “We knew that in patients who have a single site tumor in the breast, that outcomes between lumpectomy and mastectomy are the same ... But none of those trials have enrolled women with multiple sites.”

“There were no prospective data out there telling us that doing two lumpectomies in the breast was safe, so a lot of times, women were getting mastectomy for these multiple tumors, even if women had two small tumors in the breast and could easily undergo a lumpectomy with a good cosmetic result,” she said.

“So this data provides very strong evidence that we can begin treating women with small tumors in the breast who can undergo lumpectomy with a good cosmetic results without needing a mastectomy,” Dr. Barrio continued. “From a long-term quality of life standpoint, this is a big deal for women moving forward who really want to keep their breasts.”

Dr. Barrio did highlight, however, that “not everybody routinely does MRI” in women with breast cancer, including her institution, although generally she feels that “our standard imaging has gotten better,” with screening ultrasound identifying more lesions than previously.

She also believes that the numbers of women in the study who did not receive MRI are too small to “draw any definitive conclusions.

“Personally, when I have a patient with multisite disease and I’m going to keep their breasts, that to me is one indication that I would consider an MRI, to make sure that I wasn’t missing intervening disease between the two sites – that there wasn’t something else that would change my mind about doing a two-site lumpectomy,” Dr. Barrio said.

Linda M. Pak, MD, a breast cancer surgeon and surgical oncologist at NYU Langone’s Breast Cancer Center, New York, who was not involved in the study, said that the new study provides “importation information regarding the oncologic safety” of lumpectomy.

These results are “exciting to see, as they provide important information that breast-conserving surgery is safe in these patients, and that we can now share the results of this study with patients when we discuss with them their surgical options.

“I hope this will make more breast surgeons and patients comfortable with this approach and that it will increase the use of breast conservation among these patients,” Dr. Pak said.
 

Study details

In recent years, there has been increased diagnosis of multiple foci of ipsilateral breast cancer, Dr. Boughey said in her presentation. “This is both as a result of improvements in screening imaging, as well as diagnostic imaging and an increased use of preoperative breast MRI.”

Although historical, retrospective studies have shown high rates of local regional recurrences with breast-conserving therapy in women with more than one foci of breast cancer, more recent analyses have indicated that the approach is associated with “acceptable” recurrence rates.

This, Dr. Boughey explained, is due not only to improvements in breast imaging but also to better pathologic margin assessment, and improved systematic and radiation therapy.

Nevertheless, “most patients who present with two or three sites of cancer in one breast are recommended to undergo a mastectomy,” she noted.

To examine the safety of breast-conserving therapy in such patients, the team conducted a single-arm, phase 2 trial in women at least 40 years of age who had two or three foci of breast cancer, of which at least one site was invasive disease.

“While a randomized trial design would have provided stronger data, we felt that accrual to such a design would be problematic, as many patients and surgeons would not be willing to randomize,” Dr. Boughey explained.

Participants were required to have at least 2 cm of normal tissue between the lesions and disease in no more than two quadrants of the breast. They could have node-negative or N1 disease.

Women were excluded if they had foci > 5 cm on imaging; had bilateral breast cancer; had known BRCA1/2 mutations; had had prior ipsilateral breast cancer; or had received neoadjuvant therapy.

All women in the trial underwent lumpectomy with nodal staging, with adjuvant chemotherapy at the physician’s discretion, followed by whole-breast irradiation, with regional nodal irradiation again at the physician’s discretion. This was followed by systemic therapy, at the discretion of the medical oncologist.

The women were then followed up every 6 months until 5 years after the completion of whole-breast irradiation.
 

Details of the results

Dr. Boughey said that previously presented data from this study revealed that 67.6% of women achieved a margin-negative excision in a single operation, whereas 7.1% converted to mastectomy. The cosmetic outcome was rated as good or excellent at 2 years by 70.6% of women.

For the current analysis, a total of 204 women were evaluable, who had a median age of 61.1 years. Just over half (59.3%) had T1 stage disease, and 95.6% were node-negative. The majority (83.5%) had ER+/HER2- breast cancer, whereas 5.0% had ER-/HER2- disease and 11.5% had HER2+ positive tumors.

Adjuvant chemotherapy was given to 28.9% of women, whereas 89.7% of those with ER+ disease received adjuvant endocrine therapy.

The primary outcome was local recurrence rate at 5 years, which had a prespecified acceptable rate of less than 8%.

Dr. Boughey showed that, in their series, the 5-year recurrence rate was just 3.1% (95% confidence interval [CI], 1.3%-6.4%), which was “well below” the predefined “clinically significantly threshold.” This involved four cases in the ipsilateral breast, one in the skin, and one in the chest wall.

In addition to the six women with local regional recurrence, six developed contralateral breast cancer and four patients developed distant disease. There were no cases of local and distant recurrence. There were three non–breast cancer primary cancers: one gastric, one lung, and one ovarian.

Eight women died during follow-up; only one of the deaths was related to breast cancer.

Dr. Boughey explained that the small number of local recurrences was too small to identify predictive factors via multivariate analysis.

However, univariate analysis indicated that there were numerical but nonsignificant associations between local recurrence and pathologic stage T2-3 disease, pathologic nodal involvement, and surgical margins just under the negative threshold.

Among the 10 cases of ER–/HER2– breast cancer, there was one local recurrence, giving a 5-year rate of 10.0% vs. 2.6% for women with ER+/HER2– disease.

To examine the role of MRI, Dr. Boughey highlighted that although the imaging modality was initially a requirement for study entry, an amendment to the protocol in 2015 allowed 15 women who had not had MRI to take part.

The local recurrence rate in women who had undergone MRI was 1.7% vs. 22.6% in those who had not, for a hazard ratio of 13.5 (P = .002).

“While this was statistically significant, we need to bear in mind that this was a secondary unplanned analysis,” Dr. Boughey underlined.

Next, the team analyzed the impact of adjuvant endocrine therapy in the 195 women with at least one ER+ lesion, finding that it was associated with a 5-year recurrence rate of 1.9% vs. 12.5% in those who did not receive endocrine therapy, for a hazard ratio of 7.7 (P = .025).

Dr. Boughey highlighted that the study is limited by being single-arm and having only a small subset of patients without preoperative MRI, with HER2+ or ER–/HER2– disease, and with three foci of disease.

She also emphasized that “there is concern that the 5-year follow up on this protocol may be shorter than needed,” especially in women with ER+ disease.

The study was supported by the National Institutes of Health. Dr. Boughey declared relationships with Eli Lilly and Company, Symbiosis Pharma, CairnSurgical, UpToDate, and PeerView.

A version of this article first appeared on Medscape.com.

SAN ANTONIO – When choosing between chemotherapy and endocrine therapy for patients with hormone receptor (HR)+/HER2- metastatic breast cancer, allowing the results from a blood test that measures circulating tumor cell (CTC) count to overrule physician’s choice of therapy can significantly improve overall survival.

But are these results enough to change clinical practice? One expert reacting to the findings says probably not, and another pointed out that the CTC count test used in the trial (CellSearch), although approved by the Food and Drug Administration, is not widely used in clinical practice.

The findings comes from updated results from the STIC CTC study.

“When the trial was designed, the question related to the choice between single-agent endocrine therapy and chemotherapy [in] first-line therapy,” explained study presenter François-Clément Bidard, MD, PhD, professor of medical oncology at Institut Curie and Versailles Saint-Quentin University, Paris.

Since then, the first-line treatment has changed and can now can also include cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, but Dr. Bidard said the results are still clinically relevant.

Nowadays, endocrine therapy plus CDK4/6 inhibitors is the “preferred option for treatment-naive patients, but the dilemma between endocrine therapy and chemotherapy remains after disease progression on adjuvant or first-line therapy with CDK4/6 inhibitors, where current guidelines advocate in favor of endocrine therapy, despite its short-lived efficacy.”

“In that scenario, based on the STIC CTC trial results, the CTC count in combination with predictive biomarkers, whenever available, may help customize the early use of chemotherapy or antibody-drug conjugates, which are becoming more and more attractive,” Dr. Bidard said.

The research was presented here at the San Antonio Breast Cancer Symposium (SABCS).

The study involved more than 750 patients with HR+/HER2- metastatic breast cancer randomly assigned to physician choice or CTC-guided therapy, although the physician decision and the recommendation based on the CTC count was recorded in both groups.

Using the CellSearch (Menarini Silicon Biosystems) to perform the CTC count at baseline only, the team defined patients as low or high risk, with low-risk patients deemed to need only endocrine therapy and high-risk patients recommended chemotherapy.

Physicians based their decisions on current guidelines and their clinical experience.

In the 25% of cases where CTC count would recommend chemotherapy while the physician would recommend endocrine therapy, following the CTC count–based choice resulted in a 35% improvement in progression-free survival (PFS) and a 47% increase in overall survival.

In all other situations, including those when the CTC count recommended endocrine therapy in contrast to the physicians, or the approximately 60% of cases in which the two were in agreement, there was no difference in survival outcomes between the approaches.

Reacting to the findings, Nancy Chan, MD, medical oncologist and the director of breast cancer clinical research at NYU Langone’s Perlmutter Cancer Center, said that the “goal is really to understand how we can personalize treatment options for patients.”

Another aim is to avoid performing a tumor biopsy, if possible, “as that has increased morbidity for patients.”

She noted also that choosing between endocrine therapy and chemotherapy is a “big decision.” These researchers “really wanted to help some patients get less chemotherapy,” as they felt that “some patients are getting too much” as they are not really that high risk and should get endocrine therapy instead.

However, Dr. Chan said that the CTC count is a “complicated concept” and is “not something we’re all using in our clinical practice yet.”

With regard to the approximately 40% discordance between the CTC- and physician-guided choices, Dr. Chan said that clinicians are perhaps not as accurate as they believed in predicting risk when relying on the clinical or pathological features of the tumor.

On Twitter, Guilherme Nader-Marta, MD, Jules Bordet Institute, Université Libre de Bruxelles, Belgium, commented that the question behind the study was whether CTC measurement is a “clinically useful strategy for first-line treatment decision-making.”

“Amazingly,” he continued, the trial went “straight to the point” to answer the question and showed that CTC-based decisions can offer a survival benefit.

Daniel F. Hayes, MD, co-director of the Breast Oncology Program at the University of Michigan Comprehensive Cancer Center, Ann Arbor, echoed these thoughts, saying that the goals of therapy are to make patients live longer and “better.”

He said that the point of any clinical biomarker is not only to show that testing for it offers “analytical validity” but that it also provides “clinical utility” in that it can guide treatment decisions to improve outcomes.

Dr. Hayes, who was not involved in the study but has worked for many years on the development of CellSearch, said that the results do not make it clear whether measuring CTC counts meets the definition of clinical utility, but it’s “very close.”

On the other hand, the analytical validity of the test is “excellent,” and, in that context, was well-chosen, he said, adding that the endpoint of the trial “is the one most important to us: improvement in overall survival.”

Dr. Hayes noted that the magnitude of benefit from CTC-guided therapy was “moderate,” although that is a “matter of perception,” and the “level of evidence is probably 2 or 3.” Although the trial was prospective, he said, the key results were in a “relatively small” subgroup.

The question is, Dr. Hayes continued: “Is this enough to change practice? My conclusions are: probably not.”

Although patients rated as low risk based on their low CTC count avoided chemotherapy, “it’s not clear to me that this whole thing is sufficient for clinical utility in context of what we know today.” The key issue, however, is who decides whether CTC counts are measured and whether they will be used to guide therapy decisions – will it be the patient, the caregiver, an expert guidelines panel, or third party payers/society?
 

Study details

In his presentation, Dr. Bidard explained that CTC count is an FDA-approved standardized liquid biopsy biomarker, with a count of greater than or equal to 5 cells per 7.5 mL of blood deemed an adverse prognostic marker, regardless of the line of therapy, with a grade 1 level of evidence.

Previous studies have indicated that a high CTC count is strongly associated with overall survival, at a hazard ratio of 2.78.

Crucially, the CTC count “complements” and does not duplicate standard clinicopathological prognostic factors, Dr. Bidard said.

To determine the potential of the CTC count as an aid to treatment decisions, Dr. Bidard and colleagues conducted a trial in pre- and postmenopausal women with untreated HR+/HER2- metastatic breast cancer who were able to receive either endocrine therapy or chemotherapy.

They were randomly assigned to either a standard group, in which the treatment decision followed the physician’s choice, regardless of their CTC count, or to a CTC group, in which the physicians made a treatment recommendation but the choice was driven by the CTC count.

Dr. Bidard reminded the audience that the primary endpoint of PFS to demonstrate the non-inferiority of CTC versus physician treatment decisions has already been met, with the results published in 2020. Those results came from an analysis of 788 patients enrolled between February 2012 and July 2016 at 17 sites in France and showed after 42 months of follow-up that the median PFS in the CTC arm was 15.6 months versus 14 months in the physician choice arm, at a hazard ratio of 0.92.

The current pre-planned analysis involved 755 patients who were followed up for a median of 57 months by the time the trial was stopped in 2021.

In the standard treatment arm, endocrine therapy was favored by physicians in 72.7% of cases (Clin-low), while 27.3% were given chemotherapy (Clin-high).

In the CTC group, 73.5% of patients were recommended to have endocrine therapy by their physician based on their clinical characteristics (Clin-low), whereas 26.5% were suggested to have chemotherapy (Clin-high).

In contrast, 60.1% of patients in the standard arm would have received endocrine therapy based on their CTC count (CTC-low), and 39.9% chemotherapy (CTC-high), while 63.4% of those in the CTC arm were given endocrine therapy based on their CTC count (CTC-low), and 36.6% were assigned to chemotherapy (CTC-high).

Once the allocated treatment was known in both treatment groups, the physicians were free to choose between endocrine therapy (mostly a single-agent aromatase inhibitor or fulvestrant) and chemotherapy (mostly paclitaxel or capecitabine).

Although CDK4/6 inhibitors were not approved at the time of enrollment, 42.2% of patients across both treatment groups received one of these drugs as a second-line or later therapy.
 

Guiding treatment decisions

Dr. Bidard said that, overall, more patients in the CTC arm were assigned to chemotherapy, at a difference of 9.7%. There was approximately 60% concordance between physician- and CTC-guided treatment choices; in other words, patients were recommended the same treatment by the two approaches in both treatment groups.

In these patients, there was no significant difference in overall survival between the physician choice and CTC groups, at a median of 45.5 months versus 51.3 months (hazard ratio, 0.85; P = .11).

The updated PFS data revealed a median PFS of 15.7 months in the CTC group versus 13.8 months, again at a nonsignificant HR of 0.94.

These results, Dr. Bidard said, indicate that CTC-based treatment choices are “safe.”

However, there was discordance between physician and CTC-based treatment choices in around 40% of cases, meaning that the two approaches recommended different therapies.

The physician recommended endocrine therapy, in contrast to the CTC count indicating chemotherapy, in 25% of patients (Clin-low/CTC-high), whereas 13.6% of cases were recommended chemotherapy while their CTC count indicated otherwise (Clin-high/CTC-low).

In Clin-low/CTC-high patients, this resulted in 26.1% of patients in the standard group receiving endocrine therapy when their CTC count indicated chemotherapy, while 23.9% of patients in the CTC group received chemotherapy even though their physician did not recommended it.

Comparing these two groups, the researchers found that patients in the CTC group had a significantly longer PFS, at 15.7 months versus 10 months (HR, 0.65; P = .005). They also had a significantly longer median overall survival, at a median of 51.8 months versus 35.4 months with physician choice (HR, 0.53; P = .001).

Among Clin-high/CTC-low, there was no benefit from physician’s choice of chemotherapy over the CTC-guided recommendation of endocrine therapy, at an HR for PFS of 1.14 for CTC- versus physician-guided therapy (P = .54), and an HR for overall survival of 0.88 (P = .64).

Dr. Bidard highlighted that the treatment effects were seen across prespecified subgroups.

The study was funded by the Institut National du Cancer, the Institut Curie SIRIC2 program, and Menarini Silicon Biosystems. Dr. Chan reports no relevant financial relationships. Dr. Hayes and Dr. Bidard reported relationships with numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

SAN ANTONIO – When choosing between chemotherapy and endocrine therapy for patients with hormone receptor (HR)+/HER2- metastatic breast cancer, allowing the results from a blood test that measures circulating tumor cell (CTC) count to overrule physician’s choice of therapy can significantly improve overall survival.

But are these results enough to change clinical practice? One expert reacting to the findings says probably not, and another pointed out that the CTC count test used in the trial (CellSearch), although approved by the Food and Drug Administration, is not widely used in clinical practice.

The findings comes from updated results from the STIC CTC study.

“When the trial was designed, the question related to the choice between single-agent endocrine therapy and chemotherapy [in] first-line therapy,” explained study presenter François-Clément Bidard, MD, PhD, professor of medical oncology at Institut Curie and Versailles Saint-Quentin University, Paris.

Since then, the first-line treatment has changed and can now can also include cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, but Dr. Bidard said the results are still clinically relevant.

Nowadays, endocrine therapy plus CDK4/6 inhibitors is the “preferred option for treatment-naive patients, but the dilemma between endocrine therapy and chemotherapy remains after disease progression on adjuvant or first-line therapy with CDK4/6 inhibitors, where current guidelines advocate in favor of endocrine therapy, despite its short-lived efficacy.”

“In that scenario, based on the STIC CTC trial results, the CTC count in combination with predictive biomarkers, whenever available, may help customize the early use of chemotherapy or antibody-drug conjugates, which are becoming more and more attractive,” Dr. Bidard said.

The research was presented here at the San Antonio Breast Cancer Symposium (SABCS).

The study involved more than 750 patients with HR+/HER2- metastatic breast cancer randomly assigned to physician choice or CTC-guided therapy, although the physician decision and the recommendation based on the CTC count was recorded in both groups.

Using the CellSearch (Menarini Silicon Biosystems) to perform the CTC count at baseline only, the team defined patients as low or high risk, with low-risk patients deemed to need only endocrine therapy and high-risk patients recommended chemotherapy.

Physicians based their decisions on current guidelines and their clinical experience.

In the 25% of cases where CTC count would recommend chemotherapy while the physician would recommend endocrine therapy, following the CTC count–based choice resulted in a 35% improvement in progression-free survival (PFS) and a 47% increase in overall survival.

In all other situations, including those when the CTC count recommended endocrine therapy in contrast to the physicians, or the approximately 60% of cases in which the two were in agreement, there was no difference in survival outcomes between the approaches.

Reacting to the findings, Nancy Chan, MD, medical oncologist and the director of breast cancer clinical research at NYU Langone’s Perlmutter Cancer Center, said that the “goal is really to understand how we can personalize treatment options for patients.”

Another aim is to avoid performing a tumor biopsy, if possible, “as that has increased morbidity for patients.”

She noted also that choosing between endocrine therapy and chemotherapy is a “big decision.” These researchers “really wanted to help some patients get less chemotherapy,” as they felt that “some patients are getting too much” as they are not really that high risk and should get endocrine therapy instead.

However, Dr. Chan said that the CTC count is a “complicated concept” and is “not something we’re all using in our clinical practice yet.”

With regard to the approximately 40% discordance between the CTC- and physician-guided choices, Dr. Chan said that clinicians are perhaps not as accurate as they believed in predicting risk when relying on the clinical or pathological features of the tumor.

On Twitter, Guilherme Nader-Marta, MD, Jules Bordet Institute, Université Libre de Bruxelles, Belgium, commented that the question behind the study was whether CTC measurement is a “clinically useful strategy for first-line treatment decision-making.”

“Amazingly,” he continued, the trial went “straight to the point” to answer the question and showed that CTC-based decisions can offer a survival benefit.

Daniel F. Hayes, MD, co-director of the Breast Oncology Program at the University of Michigan Comprehensive Cancer Center, Ann Arbor, echoed these thoughts, saying that the goals of therapy are to make patients live longer and “better.”

He said that the point of any clinical biomarker is not only to show that testing for it offers “analytical validity” but that it also provides “clinical utility” in that it can guide treatment decisions to improve outcomes.

Dr. Hayes, who was not involved in the study but has worked for many years on the development of CellSearch, said that the results do not make it clear whether measuring CTC counts meets the definition of clinical utility, but it’s “very close.”

On the other hand, the analytical validity of the test is “excellent,” and, in that context, was well-chosen, he said, adding that the endpoint of the trial “is the one most important to us: improvement in overall survival.”

Dr. Hayes noted that the magnitude of benefit from CTC-guided therapy was “moderate,” although that is a “matter of perception,” and the “level of evidence is probably 2 or 3.” Although the trial was prospective, he said, the key results were in a “relatively small” subgroup.

The question is, Dr. Hayes continued: “Is this enough to change practice? My conclusions are: probably not.”

Although patients rated as low risk based on their low CTC count avoided chemotherapy, “it’s not clear to me that this whole thing is sufficient for clinical utility in context of what we know today.” The key issue, however, is who decides whether CTC counts are measured and whether they will be used to guide therapy decisions – will it be the patient, the caregiver, an expert guidelines panel, or third party payers/society?
 

Study details

In his presentation, Dr. Bidard explained that CTC count is an FDA-approved standardized liquid biopsy biomarker, with a count of greater than or equal to 5 cells per 7.5 mL of blood deemed an adverse prognostic marker, regardless of the line of therapy, with a grade 1 level of evidence.

Previous studies have indicated that a high CTC count is strongly associated with overall survival, at a hazard ratio of 2.78.

Crucially, the CTC count “complements” and does not duplicate standard clinicopathological prognostic factors, Dr. Bidard said.

To determine the potential of the CTC count as an aid to treatment decisions, Dr. Bidard and colleagues conducted a trial in pre- and postmenopausal women with untreated HR+/HER2- metastatic breast cancer who were able to receive either endocrine therapy or chemotherapy.

They were randomly assigned to either a standard group, in which the treatment decision followed the physician’s choice, regardless of their CTC count, or to a CTC group, in which the physicians made a treatment recommendation but the choice was driven by the CTC count.

Dr. Bidard reminded the audience that the primary endpoint of PFS to demonstrate the non-inferiority of CTC versus physician treatment decisions has already been met, with the results published in 2020. Those results came from an analysis of 788 patients enrolled between February 2012 and July 2016 at 17 sites in France and showed after 42 months of follow-up that the median PFS in the CTC arm was 15.6 months versus 14 months in the physician choice arm, at a hazard ratio of 0.92.

The current pre-planned analysis involved 755 patients who were followed up for a median of 57 months by the time the trial was stopped in 2021.

In the standard treatment arm, endocrine therapy was favored by physicians in 72.7% of cases (Clin-low), while 27.3% were given chemotherapy (Clin-high).

In the CTC group, 73.5% of patients were recommended to have endocrine therapy by their physician based on their clinical characteristics (Clin-low), whereas 26.5% were suggested to have chemotherapy (Clin-high).

In contrast, 60.1% of patients in the standard arm would have received endocrine therapy based on their CTC count (CTC-low), and 39.9% chemotherapy (CTC-high), while 63.4% of those in the CTC arm were given endocrine therapy based on their CTC count (CTC-low), and 36.6% were assigned to chemotherapy (CTC-high).

Once the allocated treatment was known in both treatment groups, the physicians were free to choose between endocrine therapy (mostly a single-agent aromatase inhibitor or fulvestrant) and chemotherapy (mostly paclitaxel or capecitabine).

Although CDK4/6 inhibitors were not approved at the time of enrollment, 42.2% of patients across both treatment groups received one of these drugs as a second-line or later therapy.
 

Guiding treatment decisions

Dr. Bidard said that, overall, more patients in the CTC arm were assigned to chemotherapy, at a difference of 9.7%. There was approximately 60% concordance between physician- and CTC-guided treatment choices; in other words, patients were recommended the same treatment by the two approaches in both treatment groups.

In these patients, there was no significant difference in overall survival between the physician choice and CTC groups, at a median of 45.5 months versus 51.3 months (hazard ratio, 0.85; P = .11).

The updated PFS data revealed a median PFS of 15.7 months in the CTC group versus 13.8 months, again at a nonsignificant HR of 0.94.

These results, Dr. Bidard said, indicate that CTC-based treatment choices are “safe.”

However, there was discordance between physician and CTC-based treatment choices in around 40% of cases, meaning that the two approaches recommended different therapies.

The physician recommended endocrine therapy, in contrast to the CTC count indicating chemotherapy, in 25% of patients (Clin-low/CTC-high), whereas 13.6% of cases were recommended chemotherapy while their CTC count indicated otherwise (Clin-high/CTC-low).

In Clin-low/CTC-high patients, this resulted in 26.1% of patients in the standard group receiving endocrine therapy when their CTC count indicated chemotherapy, while 23.9% of patients in the CTC group received chemotherapy even though their physician did not recommended it.

Comparing these two groups, the researchers found that patients in the CTC group had a significantly longer PFS, at 15.7 months versus 10 months (HR, 0.65; P = .005). They also had a significantly longer median overall survival, at a median of 51.8 months versus 35.4 months with physician choice (HR, 0.53; P = .001).

Among Clin-high/CTC-low, there was no benefit from physician’s choice of chemotherapy over the CTC-guided recommendation of endocrine therapy, at an HR for PFS of 1.14 for CTC- versus physician-guided therapy (P = .54), and an HR for overall survival of 0.88 (P = .64).

Dr. Bidard highlighted that the treatment effects were seen across prespecified subgroups.

The study was funded by the Institut National du Cancer, the Institut Curie SIRIC2 program, and Menarini Silicon Biosystems. Dr. Chan reports no relevant financial relationships. Dr. Hayes and Dr. Bidard reported relationships with numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

SAN ANTONIO – When choosing between chemotherapy and endocrine therapy for patients with hormone receptor (HR)+/HER2- metastatic breast cancer, allowing the results from a blood test that measures circulating tumor cell (CTC) count to overrule physician’s choice of therapy can significantly improve overall survival.

But are these results enough to change clinical practice? One expert reacting to the findings says probably not, and another pointed out that the CTC count test used in the trial (CellSearch), although approved by the Food and Drug Administration, is not widely used in clinical practice.

The findings comes from updated results from the STIC CTC study.

“When the trial was designed, the question related to the choice between single-agent endocrine therapy and chemotherapy [in] first-line therapy,” explained study presenter François-Clément Bidard, MD, PhD, professor of medical oncology at Institut Curie and Versailles Saint-Quentin University, Paris.

Since then, the first-line treatment has changed and can now can also include cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, but Dr. Bidard said the results are still clinically relevant.

Nowadays, endocrine therapy plus CDK4/6 inhibitors is the “preferred option for treatment-naive patients, but the dilemma between endocrine therapy and chemotherapy remains after disease progression on adjuvant or first-line therapy with CDK4/6 inhibitors, where current guidelines advocate in favor of endocrine therapy, despite its short-lived efficacy.”

“In that scenario, based on the STIC CTC trial results, the CTC count in combination with predictive biomarkers, whenever available, may help customize the early use of chemotherapy or antibody-drug conjugates, which are becoming more and more attractive,” Dr. Bidard said.

The research was presented here at the San Antonio Breast Cancer Symposium (SABCS).

The study involved more than 750 patients with HR+/HER2- metastatic breast cancer randomly assigned to physician choice or CTC-guided therapy, although the physician decision and the recommendation based on the CTC count was recorded in both groups.

Using the CellSearch (Menarini Silicon Biosystems) to perform the CTC count at baseline only, the team defined patients as low or high risk, with low-risk patients deemed to need only endocrine therapy and high-risk patients recommended chemotherapy.

Physicians based their decisions on current guidelines and their clinical experience.

In the 25% of cases where CTC count would recommend chemotherapy while the physician would recommend endocrine therapy, following the CTC count–based choice resulted in a 35% improvement in progression-free survival (PFS) and a 47% increase in overall survival.

In all other situations, including those when the CTC count recommended endocrine therapy in contrast to the physicians, or the approximately 60% of cases in which the two were in agreement, there was no difference in survival outcomes between the approaches.

Reacting to the findings, Nancy Chan, MD, medical oncologist and the director of breast cancer clinical research at NYU Langone’s Perlmutter Cancer Center, said that the “goal is really to understand how we can personalize treatment options for patients.”

Another aim is to avoid performing a tumor biopsy, if possible, “as that has increased morbidity for patients.”

She noted also that choosing between endocrine therapy and chemotherapy is a “big decision.” These researchers “really wanted to help some patients get less chemotherapy,” as they felt that “some patients are getting too much” as they are not really that high risk and should get endocrine therapy instead.

However, Dr. Chan said that the CTC count is a “complicated concept” and is “not something we’re all using in our clinical practice yet.”

With regard to the approximately 40% discordance between the CTC- and physician-guided choices, Dr. Chan said that clinicians are perhaps not as accurate as they believed in predicting risk when relying on the clinical or pathological features of the tumor.

On Twitter, Guilherme Nader-Marta, MD, Jules Bordet Institute, Université Libre de Bruxelles, Belgium, commented that the question behind the study was whether CTC measurement is a “clinically useful strategy for first-line treatment decision-making.”

“Amazingly,” he continued, the trial went “straight to the point” to answer the question and showed that CTC-based decisions can offer a survival benefit.

Daniel F. Hayes, MD, co-director of the Breast Oncology Program at the University of Michigan Comprehensive Cancer Center, Ann Arbor, echoed these thoughts, saying that the goals of therapy are to make patients live longer and “better.”

He said that the point of any clinical biomarker is not only to show that testing for it offers “analytical validity” but that it also provides “clinical utility” in that it can guide treatment decisions to improve outcomes.

Dr. Hayes, who was not involved in the study but has worked for many years on the development of CellSearch, said that the results do not make it clear whether measuring CTC counts meets the definition of clinical utility, but it’s “very close.”

On the other hand, the analytical validity of the test is “excellent,” and, in that context, was well-chosen, he said, adding that the endpoint of the trial “is the one most important to us: improvement in overall survival.”

Dr. Hayes noted that the magnitude of benefit from CTC-guided therapy was “moderate,” although that is a “matter of perception,” and the “level of evidence is probably 2 or 3.” Although the trial was prospective, he said, the key results were in a “relatively small” subgroup.

The question is, Dr. Hayes continued: “Is this enough to change practice? My conclusions are: probably not.”

Although patients rated as low risk based on their low CTC count avoided chemotherapy, “it’s not clear to me that this whole thing is sufficient for clinical utility in context of what we know today.” The key issue, however, is who decides whether CTC counts are measured and whether they will be used to guide therapy decisions – will it be the patient, the caregiver, an expert guidelines panel, or third party payers/society?
 

Study details

In his presentation, Dr. Bidard explained that CTC count is an FDA-approved standardized liquid biopsy biomarker, with a count of greater than or equal to 5 cells per 7.5 mL of blood deemed an adverse prognostic marker, regardless of the line of therapy, with a grade 1 level of evidence.

Previous studies have indicated that a high CTC count is strongly associated with overall survival, at a hazard ratio of 2.78.

Crucially, the CTC count “complements” and does not duplicate standard clinicopathological prognostic factors, Dr. Bidard said.

To determine the potential of the CTC count as an aid to treatment decisions, Dr. Bidard and colleagues conducted a trial in pre- and postmenopausal women with untreated HR+/HER2- metastatic breast cancer who were able to receive either endocrine therapy or chemotherapy.

They were randomly assigned to either a standard group, in which the treatment decision followed the physician’s choice, regardless of their CTC count, or to a CTC group, in which the physicians made a treatment recommendation but the choice was driven by the CTC count.

Dr. Bidard reminded the audience that the primary endpoint of PFS to demonstrate the non-inferiority of CTC versus physician treatment decisions has already been met, with the results published in 2020. Those results came from an analysis of 788 patients enrolled between February 2012 and July 2016 at 17 sites in France and showed after 42 months of follow-up that the median PFS in the CTC arm was 15.6 months versus 14 months in the physician choice arm, at a hazard ratio of 0.92.

The current pre-planned analysis involved 755 patients who were followed up for a median of 57 months by the time the trial was stopped in 2021.

In the standard treatment arm, endocrine therapy was favored by physicians in 72.7% of cases (Clin-low), while 27.3% were given chemotherapy (Clin-high).

In the CTC group, 73.5% of patients were recommended to have endocrine therapy by their physician based on their clinical characteristics (Clin-low), whereas 26.5% were suggested to have chemotherapy (Clin-high).

In contrast, 60.1% of patients in the standard arm would have received endocrine therapy based on their CTC count (CTC-low), and 39.9% chemotherapy (CTC-high), while 63.4% of those in the CTC arm were given endocrine therapy based on their CTC count (CTC-low), and 36.6% were assigned to chemotherapy (CTC-high).

Once the allocated treatment was known in both treatment groups, the physicians were free to choose between endocrine therapy (mostly a single-agent aromatase inhibitor or fulvestrant) and chemotherapy (mostly paclitaxel or capecitabine).

Although CDK4/6 inhibitors were not approved at the time of enrollment, 42.2% of patients across both treatment groups received one of these drugs as a second-line or later therapy.
 

Guiding treatment decisions

Dr. Bidard said that, overall, more patients in the CTC arm were assigned to chemotherapy, at a difference of 9.7%. There was approximately 60% concordance between physician- and CTC-guided treatment choices; in other words, patients were recommended the same treatment by the two approaches in both treatment groups.

In these patients, there was no significant difference in overall survival between the physician choice and CTC groups, at a median of 45.5 months versus 51.3 months (hazard ratio, 0.85; P = .11).

The updated PFS data revealed a median PFS of 15.7 months in the CTC group versus 13.8 months, again at a nonsignificant HR of 0.94.

These results, Dr. Bidard said, indicate that CTC-based treatment choices are “safe.”

However, there was discordance between physician and CTC-based treatment choices in around 40% of cases, meaning that the two approaches recommended different therapies.

The physician recommended endocrine therapy, in contrast to the CTC count indicating chemotherapy, in 25% of patients (Clin-low/CTC-high), whereas 13.6% of cases were recommended chemotherapy while their CTC count indicated otherwise (Clin-high/CTC-low).

In Clin-low/CTC-high patients, this resulted in 26.1% of patients in the standard group receiving endocrine therapy when their CTC count indicated chemotherapy, while 23.9% of patients in the CTC group received chemotherapy even though their physician did not recommended it.

Comparing these two groups, the researchers found that patients in the CTC group had a significantly longer PFS, at 15.7 months versus 10 months (HR, 0.65; P = .005). They also had a significantly longer median overall survival, at a median of 51.8 months versus 35.4 months with physician choice (HR, 0.53; P = .001).

Among Clin-high/CTC-low, there was no benefit from physician’s choice of chemotherapy over the CTC-guided recommendation of endocrine therapy, at an HR for PFS of 1.14 for CTC- versus physician-guided therapy (P = .54), and an HR for overall survival of 0.88 (P = .64).

Dr. Bidard highlighted that the treatment effects were seen across prespecified subgroups.

The study was funded by the Institut National du Cancer, the Institut Curie SIRIC2 program, and Menarini Silicon Biosystems. Dr. Chan reports no relevant financial relationships. Dr. Hayes and Dr. Bidard reported relationships with numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.