Breast Cancer

CHICAGO – Nearly all patients who were diverted from chemotherapy prior to surgery for HER2-positive early breast cancer survived without cancer recurrence for 3 years, according to new findings from a phase 2 trial.

The secondary primary endpoint results from the PHERgain study, presented at the annual meeting of the American Society of Clinical Oncology, provide more evidence to support a strategy that avoids chemotherapy as long as patients show signs of response to hormone therapy via PET scans. The results revealed that 98.8% (95% confidence interval, 96.3-100.0) of 86 patients who received treatment with trastuzumab and pertuzumab – but no chemotherapy – remained cancer free and alive 3 years after surgery (invasive disease–free survival).

“Only 1 out of 86 patients experience disease recurrence ... in those patients who never received chemotherapy,” said study lead author Javier Cortés, MD, PhD, an oncologist with Ramón y Cajal University Hospital, Madrid, during his presentation at the meeting.

As Dr. Cortés noted, HER2-targeted therapies such as trastuzumab have improved lifespans in women with HER2-positive early breast cancer, sparking interest in whether chemotherapy can be de-escalated. The PHERgain study examines whether it can be avoided entirely.

The primary endpoint results of the multicenter, open-label, noncomparative study were released in The Lancet Oncology in 2021.
 

Study methods and results

At 45 hospitals in Europe, patients with HER2-positive, stage I-IIIA, invasive, operable breast cancer were randomly assigned between 2017 and 2019 to receive chemotherapy prior to surgery (n = 71, group A) or to only receive hormone therapy with trastuzumab and pertuzumab, unless PET scans suggested they needed chemotherapy because they weren’t properly responding (n = 285, group B).

At a median follow-up of 5.7 months, 86 patients in the latter group had a pathological complete response and therefore met the first primary endpoint.

The new analysis tracked patients for 3 years after they underwent surgery (n = 63 and 267 for patients in groups A and B, respectively). As previously noted, at a median follow-up of 43.3 months (range, 2.4-63.0 months), only 1 of 86 patients in group B who didn’t receive chemotherapy had a recurrence of cancer (a locoregional ipsilateral recurrence). The 98.8% invasive disease–free survival rate was higher that what was seen for patients in group B as a whole (95.4% invasive disease–free survival, 95% CI, 92.8%-98.0%, P < .001). The 95.4% met the study’s second primary endpoint.

Treatment-related adverse events were higher in the group that received chemotherapy only (group A) versus group B (experiencing an adverse event grade of at least 3, 61.8% vs. 32.9%, respectively, P < .001; serious adverse events, 27.9% vs. 13.8%, respectively; P = .01). Those in group B who didn’t receive any chemotherapy had very few treatment-related adverse events that were considered being greater than a grade 3 (1.2%) and no treatment-related serious adverse events. The researchers reported that there were no treatment-related deaths.

In an interview, Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, and cochair of the session where the study data was presented, said the “intriguing and meaningful [findings] highlight the fact that not everyone may need chemotherapy.” In the big picture, the results reflect a movement toward “individualized, personalized medicine, and moving away from one size fits all.”

Should clinicians embrace the study’s strategy, and what are the costs?

“There may be a need for additional evaluation in a large phase 3 trial,” Dr. Kalinsky said.

There was no discussion about cost during the ASCO presentation. However, Dr. Kalinsky noted that there will be cost savings if patients don’t need chemotherapy. But he added that insurers in the United States don’t always cover the PET scans that are needed to evaluate whether patients are responding to hormone therapy.

The study is funded by Roche and sponsored by MedSIR. Dr. Cortes has multiple disclosures, including stock/other ownership in Leuko, MedSIR, and Nektar and honoraria from AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung. Dr. Kalinsky has no disclosures.

CHICAGO – Nearly all patients who were diverted from chemotherapy prior to surgery for HER2-positive early breast cancer survived without cancer recurrence for 3 years, according to new findings from a phase 2 trial.

The secondary primary endpoint results from the PHERgain study, presented at the annual meeting of the American Society of Clinical Oncology, provide more evidence to support a strategy that avoids chemotherapy as long as patients show signs of response to hormone therapy via PET scans. The results revealed that 98.8% (95% confidence interval, 96.3-100.0) of 86 patients who received treatment with trastuzumab and pertuzumab – but no chemotherapy – remained cancer free and alive 3 years after surgery (invasive disease–free survival).

“Only 1 out of 86 patients experience disease recurrence ... in those patients who never received chemotherapy,” said study lead author Javier Cortés, MD, PhD, an oncologist with Ramón y Cajal University Hospital, Madrid, during his presentation at the meeting.

As Dr. Cortés noted, HER2-targeted therapies such as trastuzumab have improved lifespans in women with HER2-positive early breast cancer, sparking interest in whether chemotherapy can be de-escalated. The PHERgain study examines whether it can be avoided entirely.

The primary endpoint results of the multicenter, open-label, noncomparative study were released in The Lancet Oncology in 2021.
 

Study methods and results

At 45 hospitals in Europe, patients with HER2-positive, stage I-IIIA, invasive, operable breast cancer were randomly assigned between 2017 and 2019 to receive chemotherapy prior to surgery (n = 71, group A) or to only receive hormone therapy with trastuzumab and pertuzumab, unless PET scans suggested they needed chemotherapy because they weren’t properly responding (n = 285, group B).

At a median follow-up of 5.7 months, 86 patients in the latter group had a pathological complete response and therefore met the first primary endpoint.

The new analysis tracked patients for 3 years after they underwent surgery (n = 63 and 267 for patients in groups A and B, respectively). As previously noted, at a median follow-up of 43.3 months (range, 2.4-63.0 months), only 1 of 86 patients in group B who didn’t receive chemotherapy had a recurrence of cancer (a locoregional ipsilateral recurrence). The 98.8% invasive disease–free survival rate was higher that what was seen for patients in group B as a whole (95.4% invasive disease–free survival, 95% CI, 92.8%-98.0%, P < .001). The 95.4% met the study’s second primary endpoint.

Treatment-related adverse events were higher in the group that received chemotherapy only (group A) versus group B (experiencing an adverse event grade of at least 3, 61.8% vs. 32.9%, respectively, P < .001; serious adverse events, 27.9% vs. 13.8%, respectively; P = .01). Those in group B who didn’t receive any chemotherapy had very few treatment-related adverse events that were considered being greater than a grade 3 (1.2%) and no treatment-related serious adverse events. The researchers reported that there were no treatment-related deaths.

In an interview, Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, and cochair of the session where the study data was presented, said the “intriguing and meaningful [findings] highlight the fact that not everyone may need chemotherapy.” In the big picture, the results reflect a movement toward “individualized, personalized medicine, and moving away from one size fits all.”

Should clinicians embrace the study’s strategy, and what are the costs?

“There may be a need for additional evaluation in a large phase 3 trial,” Dr. Kalinsky said.

There was no discussion about cost during the ASCO presentation. However, Dr. Kalinsky noted that there will be cost savings if patients don’t need chemotherapy. But he added that insurers in the United States don’t always cover the PET scans that are needed to evaluate whether patients are responding to hormone therapy.

The study is funded by Roche and sponsored by MedSIR. Dr. Cortes has multiple disclosures, including stock/other ownership in Leuko, MedSIR, and Nektar and honoraria from AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung. Dr. Kalinsky has no disclosures.

CHICAGO – Nearly all patients who were diverted from chemotherapy prior to surgery for HER2-positive early breast cancer survived without cancer recurrence for 3 years, according to new findings from a phase 2 trial.

The secondary primary endpoint results from the PHERgain study, presented at the annual meeting of the American Society of Clinical Oncology, provide more evidence to support a strategy that avoids chemotherapy as long as patients show signs of response to hormone therapy via PET scans. The results revealed that 98.8% (95% confidence interval, 96.3-100.0) of 86 patients who received treatment with trastuzumab and pertuzumab – but no chemotherapy – remained cancer free and alive 3 years after surgery (invasive disease–free survival).

“Only 1 out of 86 patients experience disease recurrence ... in those patients who never received chemotherapy,” said study lead author Javier Cortés, MD, PhD, an oncologist with Ramón y Cajal University Hospital, Madrid, during his presentation at the meeting.

As Dr. Cortés noted, HER2-targeted therapies such as trastuzumab have improved lifespans in women with HER2-positive early breast cancer, sparking interest in whether chemotherapy can be de-escalated. The PHERgain study examines whether it can be avoided entirely.

The primary endpoint results of the multicenter, open-label, noncomparative study were released in The Lancet Oncology in 2021.
 

Study methods and results

At 45 hospitals in Europe, patients with HER2-positive, stage I-IIIA, invasive, operable breast cancer were randomly assigned between 2017 and 2019 to receive chemotherapy prior to surgery (n = 71, group A) or to only receive hormone therapy with trastuzumab and pertuzumab, unless PET scans suggested they needed chemotherapy because they weren’t properly responding (n = 285, group B).

At a median follow-up of 5.7 months, 86 patients in the latter group had a pathological complete response and therefore met the first primary endpoint.

The new analysis tracked patients for 3 years after they underwent surgery (n = 63 and 267 for patients in groups A and B, respectively). As previously noted, at a median follow-up of 43.3 months (range, 2.4-63.0 months), only 1 of 86 patients in group B who didn’t receive chemotherapy had a recurrence of cancer (a locoregional ipsilateral recurrence). The 98.8% invasive disease–free survival rate was higher that what was seen for patients in group B as a whole (95.4% invasive disease–free survival, 95% CI, 92.8%-98.0%, P < .001). The 95.4% met the study’s second primary endpoint.

Treatment-related adverse events were higher in the group that received chemotherapy only (group A) versus group B (experiencing an adverse event grade of at least 3, 61.8% vs. 32.9%, respectively, P < .001; serious adverse events, 27.9% vs. 13.8%, respectively; P = .01). Those in group B who didn’t receive any chemotherapy had very few treatment-related adverse events that were considered being greater than a grade 3 (1.2%) and no treatment-related serious adverse events. The researchers reported that there were no treatment-related deaths.

In an interview, Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, and cochair of the session where the study data was presented, said the “intriguing and meaningful [findings] highlight the fact that not everyone may need chemotherapy.” In the big picture, the results reflect a movement toward “individualized, personalized medicine, and moving away from one size fits all.”

Should clinicians embrace the study’s strategy, and what are the costs?

“There may be a need for additional evaluation in a large phase 3 trial,” Dr. Kalinsky said.

There was no discussion about cost during the ASCO presentation. However, Dr. Kalinsky noted that there will be cost savings if patients don’t need chemotherapy. But he added that insurers in the United States don’t always cover the PET scans that are needed to evaluate whether patients are responding to hormone therapy.

The study is funded by Roche and sponsored by MedSIR. Dr. Cortes has multiple disclosures, including stock/other ownership in Leuko, MedSIR, and Nektar and honoraria from AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung. Dr. Kalinsky has no disclosures.

CHICAGO – A new meta-analysis of 25 studies dating back to 1948 provides more evidence linking ovarian suppression/ablation in premenopausal women to less recurrence and more survival in the long term after breast cancer.

Those who didn’t take tamoxifen – a standard treatment today – seemed to gain an especially large benefit.

The randomized studies, which included 14,999 subjects, suggest that ovarian suppression/ablation can provide a “substantial and persistent benefit for premenopausal women,” said study lead author and medical statistician Richard G. Gray, MA, MSc, of the University of Oxford (England), in a presentation at the annual meeting of the American Society of Clinical Oncology.

The study authors sought to better understand the value of ovarian suppression/ablation, which may prevent estrogen from stimulating residual cancer after treatment. According to the study abstract, premenopausal women with estrogen receptor–positive tumors may be at special risk of cancer recurrence because of this phenomenon.

Recently published research has supported hormone therapy targeting the ovaries in this population.

“Ovarian suppression with an aromatase inhibitor should become the preferred initial hormone therapy recommendation for all premenopausal women with high-risk (i.e., grade 3, T2, and age less than 35 years) estrogen receptor–positive breast cancer,” declared a 2022 editorial in the Journal of Clinical Oncology that noted the positive findings of a 13-year follow-up analysis of 2 studies.
 

Study methods and results

For the meta-analysis released at ASCO, researchers examined 25 trials that randomized women with breast cancer who were premenopausal. In some cases, the women went through menopause during the trials, and in some other cases, ovarian suppression/ablation brought on early menopause.

Among women who had received no chemotherapy or remained premenopausal after chemotherapy (n = 7,213), cancer recurred within 15 years in 41% of the controls and 28.9% of the ovarian suppression/ablation group, (relative risk, 0.70; 95% confidence interval, 0.63-0.78; P < .00001).

Among these same women, breast cancer mortality at 20 years was 34.7% in the controls and 23.8% in the ovarian suppression/ablation group (RR, 0.71; 95% CI, 0.62-0.81; P < .00001).

The researchers also looked at the same group of women and divided it into those who didn’t take tamoxifen (2,362) and those who did take tamoxifen (4,851). The drug is now the preferred option “for treatment of breast cancer.”

Among those who did not take tamoxifen, the recurrence rate at 15 years was 56.5% among controls versus 39.0% among those in the ovarian suppression/ablation group (RR, 0.61; 95% CI, 0.52-0.72; P < .00001). The gap shrunk in those who did take tamoxifen: recurrence occurred in 30.3% of the control group and 25.8% of the ovarian suppression/ablation group (RR, 0.80; 95% CI, 0.70-0.93; P = .002).
 

Tamoxifen on its own seems to have powerful positive effect

The findings suggest that tamoxifen on its own has a powerful positive effect, leaving less extra benefit for ovarian suppression/ablation to provide, said Mr. Gray.

The meta-analysis didn’t examine cost or cost-effectiveness.

Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, cochair of the session where the meta-analysis data was presented, said in an interview that the new research shows that “patients can really benefit from ovarian function suppression.” Even so, recent trials suggested that the strategy is uncommon, used by less than 20% of high-risk patients.

Dr. Kalinsky noted that suppressing the ovaries with medication or removing the ovaries entirely can cause early menopause and eliminate fertility.

“There can be definitely be side effects like hot flashes and tolerability issues,” he said, “along with an impact on quality of life.”

According to the U.K. organization Breast Cancer Now,“ovarian suppression achieved by hormone therapy or surgery is more likely to cause menopausal symptoms than a natural menopause.” In addition, “research has shown that younger women are more likely to stop taking hormone therapy early if they don’t get help with possible side effects.”

It’s important for patients and providers to have full discussions about possible strategies, Dr. Kalinsky said.

No information about study funding was provided. Dr. Kalinsky and Mr. Gray had no financial conflicts.

CHICAGO – A new meta-analysis of 25 studies dating back to 1948 provides more evidence linking ovarian suppression/ablation in premenopausal women to less recurrence and more survival in the long term after breast cancer.

Those who didn’t take tamoxifen – a standard treatment today – seemed to gain an especially large benefit.

The randomized studies, which included 14,999 subjects, suggest that ovarian suppression/ablation can provide a “substantial and persistent benefit for premenopausal women,” said study lead author and medical statistician Richard G. Gray, MA, MSc, of the University of Oxford (England), in a presentation at the annual meeting of the American Society of Clinical Oncology.

The study authors sought to better understand the value of ovarian suppression/ablation, which may prevent estrogen from stimulating residual cancer after treatment. According to the study abstract, premenopausal women with estrogen receptor–positive tumors may be at special risk of cancer recurrence because of this phenomenon.

Recently published research has supported hormone therapy targeting the ovaries in this population.

“Ovarian suppression with an aromatase inhibitor should become the preferred initial hormone therapy recommendation for all premenopausal women with high-risk (i.e., grade 3, T2, and age less than 35 years) estrogen receptor–positive breast cancer,” declared a 2022 editorial in the Journal of Clinical Oncology that noted the positive findings of a 13-year follow-up analysis of 2 studies.
 

Study methods and results

For the meta-analysis released at ASCO, researchers examined 25 trials that randomized women with breast cancer who were premenopausal. In some cases, the women went through menopause during the trials, and in some other cases, ovarian suppression/ablation brought on early menopause.

Among women who had received no chemotherapy or remained premenopausal after chemotherapy (n = 7,213), cancer recurred within 15 years in 41% of the controls and 28.9% of the ovarian suppression/ablation group, (relative risk, 0.70; 95% confidence interval, 0.63-0.78; P < .00001).

Among these same women, breast cancer mortality at 20 years was 34.7% in the controls and 23.8% in the ovarian suppression/ablation group (RR, 0.71; 95% CI, 0.62-0.81; P < .00001).

The researchers also looked at the same group of women and divided it into those who didn’t take tamoxifen (2,362) and those who did take tamoxifen (4,851). The drug is now the preferred option “for treatment of breast cancer.”

Among those who did not take tamoxifen, the recurrence rate at 15 years was 56.5% among controls versus 39.0% among those in the ovarian suppression/ablation group (RR, 0.61; 95% CI, 0.52-0.72; P < .00001). The gap shrunk in those who did take tamoxifen: recurrence occurred in 30.3% of the control group and 25.8% of the ovarian suppression/ablation group (RR, 0.80; 95% CI, 0.70-0.93; P = .002).
 

Tamoxifen on its own seems to have powerful positive effect

The findings suggest that tamoxifen on its own has a powerful positive effect, leaving less extra benefit for ovarian suppression/ablation to provide, said Mr. Gray.

The meta-analysis didn’t examine cost or cost-effectiveness.

Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, cochair of the session where the meta-analysis data was presented, said in an interview that the new research shows that “patients can really benefit from ovarian function suppression.” Even so, recent trials suggested that the strategy is uncommon, used by less than 20% of high-risk patients.

Dr. Kalinsky noted that suppressing the ovaries with medication or removing the ovaries entirely can cause early menopause and eliminate fertility.

“There can be definitely be side effects like hot flashes and tolerability issues,” he said, “along with an impact on quality of life.”

According to the U.K. organization Breast Cancer Now,“ovarian suppression achieved by hormone therapy or surgery is more likely to cause menopausal symptoms than a natural menopause.” In addition, “research has shown that younger women are more likely to stop taking hormone therapy early if they don’t get help with possible side effects.”

It’s important for patients and providers to have full discussions about possible strategies, Dr. Kalinsky said.

No information about study funding was provided. Dr. Kalinsky and Mr. Gray had no financial conflicts.

CHICAGO – A new meta-analysis of 25 studies dating back to 1948 provides more evidence linking ovarian suppression/ablation in premenopausal women to less recurrence and more survival in the long term after breast cancer.

Those who didn’t take tamoxifen – a standard treatment today – seemed to gain an especially large benefit.

The randomized studies, which included 14,999 subjects, suggest that ovarian suppression/ablation can provide a “substantial and persistent benefit for premenopausal women,” said study lead author and medical statistician Richard G. Gray, MA, MSc, of the University of Oxford (England), in a presentation at the annual meeting of the American Society of Clinical Oncology.

The study authors sought to better understand the value of ovarian suppression/ablation, which may prevent estrogen from stimulating residual cancer after treatment. According to the study abstract, premenopausal women with estrogen receptor–positive tumors may be at special risk of cancer recurrence because of this phenomenon.

Recently published research has supported hormone therapy targeting the ovaries in this population.

“Ovarian suppression with an aromatase inhibitor should become the preferred initial hormone therapy recommendation for all premenopausal women with high-risk (i.e., grade 3, T2, and age less than 35 years) estrogen receptor–positive breast cancer,” declared a 2022 editorial in the Journal of Clinical Oncology that noted the positive findings of a 13-year follow-up analysis of 2 studies.
 

Study methods and results

For the meta-analysis released at ASCO, researchers examined 25 trials that randomized women with breast cancer who were premenopausal. In some cases, the women went through menopause during the trials, and in some other cases, ovarian suppression/ablation brought on early menopause.

Among women who had received no chemotherapy or remained premenopausal after chemotherapy (n = 7,213), cancer recurred within 15 years in 41% of the controls and 28.9% of the ovarian suppression/ablation group, (relative risk, 0.70; 95% confidence interval, 0.63-0.78; P < .00001).

Among these same women, breast cancer mortality at 20 years was 34.7% in the controls and 23.8% in the ovarian suppression/ablation group (RR, 0.71; 95% CI, 0.62-0.81; P < .00001).

The researchers also looked at the same group of women and divided it into those who didn’t take tamoxifen (2,362) and those who did take tamoxifen (4,851). The drug is now the preferred option “for treatment of breast cancer.”

Among those who did not take tamoxifen, the recurrence rate at 15 years was 56.5% among controls versus 39.0% among those in the ovarian suppression/ablation group (RR, 0.61; 95% CI, 0.52-0.72; P < .00001). The gap shrunk in those who did take tamoxifen: recurrence occurred in 30.3% of the control group and 25.8% of the ovarian suppression/ablation group (RR, 0.80; 95% CI, 0.70-0.93; P = .002).
 

Tamoxifen on its own seems to have powerful positive effect

The findings suggest that tamoxifen on its own has a powerful positive effect, leaving less extra benefit for ovarian suppression/ablation to provide, said Mr. Gray.

The meta-analysis didn’t examine cost or cost-effectiveness.

Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, cochair of the session where the meta-analysis data was presented, said in an interview that the new research shows that “patients can really benefit from ovarian function suppression.” Even so, recent trials suggested that the strategy is uncommon, used by less than 20% of high-risk patients.

Dr. Kalinsky noted that suppressing the ovaries with medication or removing the ovaries entirely can cause early menopause and eliminate fertility.

“There can be definitely be side effects like hot flashes and tolerability issues,” he said, “along with an impact on quality of life.”

According to the U.K. organization Breast Cancer Now,“ovarian suppression achieved by hormone therapy or surgery is more likely to cause menopausal symptoms than a natural menopause.” In addition, “research has shown that younger women are more likely to stop taking hormone therapy early if they don’t get help with possible side effects.”

It’s important for patients and providers to have full discussions about possible strategies, Dr. Kalinsky said.

No information about study funding was provided. Dr. Kalinsky and Mr. Gray had no financial conflicts.

The federal government is reconsidering a decision that breast cancer patients, plastic surgeons, and members of Congress have protested would limit women’s options for reconstructive surgery.

On June 1, the Centers for Medicare & Medicaid Services plans to reexamine how doctors are paid for a type of breast reconstruction known as DIEP flap, in which skin, fat, and blood vessels are harvested from a woman’s abdomen to create a new breast.

The procedure offers potential advantages over implants and operations that take muscle from the abdomen. But it’s also more expensive. If patients go outside an insurance network for the operation, it can cost more than $50,000. And, if insurers pay significantly less for the surgery as a result of the government’s decision, some in-network surgeons would stop offering it, a plastic surgeons group has argued.

The DIEP flap controversy, spotlighted by CBS News in January, illustrates arcane and indirect ways the federal government can influence which medical options are available – even to people with private insurance. Often, the answers come down to billing codes – which identify specific medical services on forms doctors submit for reimbursement – and the competing pleas of groups whose interests are riding on them.

Medical coding is the backbone for “how business gets done in medicine,” said Karen Joynt Maddox, MD, MPH, a physician at Washington University in St. Louis who researches health economics and policy.

CMS, the agency overseeing Medicare and Medicaid, maintains a list of codes representing thousands of medical services and products. It regularly evaluates whether to add codes or revise or remove existing ones. In 2022, it decided to eliminate a code that has enabled doctors to collect much more money for DIEP flap operations than for simpler types of breast reconstruction.

In 2006, CMS established an “S” code – S2068 – for what was then a relatively new procedure: breast reconstructions with deep inferior epigastric perforator flap (DIEP flap). S codes temporarily fill gaps in a parallel system of billing codes known as CPT codes, which are maintained by the American Medical Association.

Codes don’t dictate the amounts private insurers pay for medical services; those reimbursements are generally worked out between insurance companies and medical providers. However, using the narrowly targeted S code, doctors and hospitals have been able to distinguish DIEP flap surgeries, which require complex microsurgical skills, from other forms of breast reconstruction that take less time to perform and generally yield lower insurance reimbursements.

CMS announced in 2022 that it planned to eliminate the S code at the end of 2024 – a move some doctors say would slash the amount surgeons are paid. (To be precise, CMS announced it would eliminate a series of three S codes for similar procedures, but some of the more outspoken critics have focused on one of them, S2068.) The agency’s decision is already changing the landscape of reconstructive surgery and creating anxiety for breast cancer patients.

Kate Getz, a single mother in Morton, Ill., learned she had cancer in January at age 30. As she grappled with her diagnosis, it was overwhelming to think about what her body would look like over the long term. She pictured herself getting married one day and wondered “how on earth I would be able to wear a wedding dress with only having one breast left,” she said.

She thought a DIEP flap was her best option and worried about having to undergo repeated surgeries if she got implants instead. Implants generally need to be replaced every 10 years or so. But after she spent more than a month trying to get answers about how her DIEP flap surgery would be covered, Ms. Getz’s insurer, Cigna, informed her it would use a lower-paying CPT code to reimburse her physician, Ms. Getz said. As far as she could see, that would have made it impossible for Ms. Getz to obtain the surgery.

Paying out of pocket was “not even an option.”

“I’m a single mom. We get by, right? But I’m not, not wealthy by any means,” she said.

Cost is not necessarily the only hurdle patients seeking DIEP flaps must overcome. Citing the complexity of the procedure, Ms. Getz said, a local plastic surgeon told her it would be difficult for him to perform. She ended up traveling from Illinois to Texas for the surgery.

The government’s plan to eliminate the three S codes was driven by the Blue Cross Blue Shield Association, a major lobbying organization for health insurance companies. In 2021, the group asked CMS to discontinue the codes, arguing that they were no longer needed because the AMA had updated a CPT code to explicitly include DIEP flap surgery and the related operations, according to a CMS document.

For years, the AMA advised doctors that the CPT code was appropriate for DIEP flap procedures. But after the government’s decision, at least two major insurance companies told doctors they would no longer reimburse them under the higher-paying codes, prompting a backlash.

Physicians and advocacy groups for breast cancer patients, such as the nonprofit organization Susan G. Komen, have argued that many plastic surgeons would stop providing DIEP flap procedures for women with private insurance because they wouldn’t get paid enough.

Lawmakers from both parties have asked the agency to keep the S code, including Rep. Debbie Wasserman Schultz (D-Fla.) and Sen. Amy Klobuchar (D-Minn.), who have had breast cancer, and Sen. Marsha Blackburn (R-Tenn.).

CMS at its June 1 meeting will consider whether to keep the three S codes or delay their expiration.

In a May 30 statement, Blue Cross Blue Shield Association spokesperson Kelly Parsons reiterated the organization’s view that “there is no longer a need to keep the S codes.”

In a profit-driven health care system, there’s a tug of war over reimbursements between providers and insurance companies, often at the expense of patients, said Dr. Joynt Maddox.

“We’re in this sort of constant battle” between hospital chains and insurance companies “about who’s going to wield more power at the bargaining table,” Dr. Joynt Maddox said. “And the clinical piece of that often gets lost, because it’s not often the clinical benefit and the clinical priority and the patient centeredness that’s at the middle of these conversations.”

Elisabeth Potter, MD, a plastic surgeon who specializes in DIEP flap surgeries, decided to perform Ms. Getz’s surgery at whatever price Cigna would pay.

According to Fair Health, a nonprofit that provides information on health care costs, in Austin, Tex. – where Dr. Potter is based – an insurer might pay an in-network doctor $9,323 for the surgery when it’s billed using the CPT code and $18,037 under the S code. Those amounts are not averages; rather, Fair Health estimated that 80% of payment rates are lower than or equal to those amounts.

Dr. Potter said her Cigna reimbursement “is significantly lower.”

Weeks before her May surgery, Ms. Getz received big news – Cigna had reversed itself and would cover her surgery under the S code. It “felt like a real victory,” she said.

But she still fears for other patients.

“I’m still asking these companies to do right by women,” Ms. Getz said. “I’m still asking them to provide the procedures we need to reimburse them at rates where women have access to them regardless of their wealth.”

In a statement, Cigna spokesperson Justine Sessions said the insurer remains “committed to ensuring that our customers have affordable coverage and access to the full range of breast reconstruction procedures and to quality surgeons who perform these complex surgeries.”

Medical costs that health insurers cover generally are passed along to consumers in the form of premiums, deductibles, and other out-of-pocket expenses.

For any type of breast reconstruction, there are benefits, risks, and trade-offs. A 2018 paper published in JAMA Surgery found that women who underwent DIEP flap surgery had higher odds of developing “reoperative complications” within 2 years than those who received artificial implants. However, DIEP flaps had lower odds of infection than implants.

Implants carry risks of additional surgery, pain, rupture, and even an uncommon type of immune system cancer.

Other flap procedures that take muscle from the abdomen can leave women with weakened abdominal walls and increase their risk of developing a hernia.

Academic research shows that insurance reimbursement affects which women can access DIEP flap breast reconstruction, creating a two-tiered system for private health insurance versus government programs like Medicare and Medicaid. Private insurance generally pays physicians more than government coverage, and Medicare doesn’t use S codes.

Lynn Damitz, a physician and board vice president of health policy and advocacy for the American Society of Plastic Surgeons, said the group supports continuing the S code temporarily or indefinitely. If reimbursements drop, some doctors won’t perform DIEP flaps anymore.

A study published in February found that, of patients who used their own tissue for breast reconstruction, privately insured patients were more likely than publicly insured patients to receive DIEP flap reconstruction.

To Dr. Potter, that shows what will happen if private insurance payments plummet. “If you’re a Medicare provider and you’re not paid to do DIEP flaps, you never tell a patient that it’s an option. You won’t perform it,” Dr. Potter said. “If you take private insurance and all of a sudden your reimbursement rate is cut from $15,000 down to $3,500, you’re not going to do that surgery. And I’m not saying that that’s the right thing to do, but that’s what happens.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The federal government is reconsidering a decision that breast cancer patients, plastic surgeons, and members of Congress have protested would limit women’s options for reconstructive surgery.

On June 1, the Centers for Medicare & Medicaid Services plans to reexamine how doctors are paid for a type of breast reconstruction known as DIEP flap, in which skin, fat, and blood vessels are harvested from a woman’s abdomen to create a new breast.

The procedure offers potential advantages over implants and operations that take muscle from the abdomen. But it’s also more expensive. If patients go outside an insurance network for the operation, it can cost more than $50,000. And, if insurers pay significantly less for the surgery as a result of the government’s decision, some in-network surgeons would stop offering it, a plastic surgeons group has argued.

The DIEP flap controversy, spotlighted by CBS News in January, illustrates arcane and indirect ways the federal government can influence which medical options are available – even to people with private insurance. Often, the answers come down to billing codes – which identify specific medical services on forms doctors submit for reimbursement – and the competing pleas of groups whose interests are riding on them.

Medical coding is the backbone for “how business gets done in medicine,” said Karen Joynt Maddox, MD, MPH, a physician at Washington University in St. Louis who researches health economics and policy.

CMS, the agency overseeing Medicare and Medicaid, maintains a list of codes representing thousands of medical services and products. It regularly evaluates whether to add codes or revise or remove existing ones. In 2022, it decided to eliminate a code that has enabled doctors to collect much more money for DIEP flap operations than for simpler types of breast reconstruction.

In 2006, CMS established an “S” code – S2068 – for what was then a relatively new procedure: breast reconstructions with deep inferior epigastric perforator flap (DIEP flap). S codes temporarily fill gaps in a parallel system of billing codes known as CPT codes, which are maintained by the American Medical Association.

Codes don’t dictate the amounts private insurers pay for medical services; those reimbursements are generally worked out between insurance companies and medical providers. However, using the narrowly targeted S code, doctors and hospitals have been able to distinguish DIEP flap surgeries, which require complex microsurgical skills, from other forms of breast reconstruction that take less time to perform and generally yield lower insurance reimbursements.

CMS announced in 2022 that it planned to eliminate the S code at the end of 2024 – a move some doctors say would slash the amount surgeons are paid. (To be precise, CMS announced it would eliminate a series of three S codes for similar procedures, but some of the more outspoken critics have focused on one of them, S2068.) The agency’s decision is already changing the landscape of reconstructive surgery and creating anxiety for breast cancer patients.

Kate Getz, a single mother in Morton, Ill., learned she had cancer in January at age 30. As she grappled with her diagnosis, it was overwhelming to think about what her body would look like over the long term. She pictured herself getting married one day and wondered “how on earth I would be able to wear a wedding dress with only having one breast left,” she said.

She thought a DIEP flap was her best option and worried about having to undergo repeated surgeries if she got implants instead. Implants generally need to be replaced every 10 years or so. But after she spent more than a month trying to get answers about how her DIEP flap surgery would be covered, Ms. Getz’s insurer, Cigna, informed her it would use a lower-paying CPT code to reimburse her physician, Ms. Getz said. As far as she could see, that would have made it impossible for Ms. Getz to obtain the surgery.

Paying out of pocket was “not even an option.”

“I’m a single mom. We get by, right? But I’m not, not wealthy by any means,” she said.

Cost is not necessarily the only hurdle patients seeking DIEP flaps must overcome. Citing the complexity of the procedure, Ms. Getz said, a local plastic surgeon told her it would be difficult for him to perform. She ended up traveling from Illinois to Texas for the surgery.

The government’s plan to eliminate the three S codes was driven by the Blue Cross Blue Shield Association, a major lobbying organization for health insurance companies. In 2021, the group asked CMS to discontinue the codes, arguing that they were no longer needed because the AMA had updated a CPT code to explicitly include DIEP flap surgery and the related operations, according to a CMS document.

For years, the AMA advised doctors that the CPT code was appropriate for DIEP flap procedures. But after the government’s decision, at least two major insurance companies told doctors they would no longer reimburse them under the higher-paying codes, prompting a backlash.

Physicians and advocacy groups for breast cancer patients, such as the nonprofit organization Susan G. Komen, have argued that many plastic surgeons would stop providing DIEP flap procedures for women with private insurance because they wouldn’t get paid enough.

Lawmakers from both parties have asked the agency to keep the S code, including Rep. Debbie Wasserman Schultz (D-Fla.) and Sen. Amy Klobuchar (D-Minn.), who have had breast cancer, and Sen. Marsha Blackburn (R-Tenn.).

CMS at its June 1 meeting will consider whether to keep the three S codes or delay their expiration.

In a May 30 statement, Blue Cross Blue Shield Association spokesperson Kelly Parsons reiterated the organization’s view that “there is no longer a need to keep the S codes.”

In a profit-driven health care system, there’s a tug of war over reimbursements between providers and insurance companies, often at the expense of patients, said Dr. Joynt Maddox.

“We’re in this sort of constant battle” between hospital chains and insurance companies “about who’s going to wield more power at the bargaining table,” Dr. Joynt Maddox said. “And the clinical piece of that often gets lost, because it’s not often the clinical benefit and the clinical priority and the patient centeredness that’s at the middle of these conversations.”

Elisabeth Potter, MD, a plastic surgeon who specializes in DIEP flap surgeries, decided to perform Ms. Getz’s surgery at whatever price Cigna would pay.

According to Fair Health, a nonprofit that provides information on health care costs, in Austin, Tex. – where Dr. Potter is based – an insurer might pay an in-network doctor $9,323 for the surgery when it’s billed using the CPT code and $18,037 under the S code. Those amounts are not averages; rather, Fair Health estimated that 80% of payment rates are lower than or equal to those amounts.

Dr. Potter said her Cigna reimbursement “is significantly lower.”

Weeks before her May surgery, Ms. Getz received big news – Cigna had reversed itself and would cover her surgery under the S code. It “felt like a real victory,” she said.

But she still fears for other patients.

“I’m still asking these companies to do right by women,” Ms. Getz said. “I’m still asking them to provide the procedures we need to reimburse them at rates where women have access to them regardless of their wealth.”

In a statement, Cigna spokesperson Justine Sessions said the insurer remains “committed to ensuring that our customers have affordable coverage and access to the full range of breast reconstruction procedures and to quality surgeons who perform these complex surgeries.”

Medical costs that health insurers cover generally are passed along to consumers in the form of premiums, deductibles, and other out-of-pocket expenses.

For any type of breast reconstruction, there are benefits, risks, and trade-offs. A 2018 paper published in JAMA Surgery found that women who underwent DIEP flap surgery had higher odds of developing “reoperative complications” within 2 years than those who received artificial implants. However, DIEP flaps had lower odds of infection than implants.

Implants carry risks of additional surgery, pain, rupture, and even an uncommon type of immune system cancer.

Other flap procedures that take muscle from the abdomen can leave women with weakened abdominal walls and increase their risk of developing a hernia.

Academic research shows that insurance reimbursement affects which women can access DIEP flap breast reconstruction, creating a two-tiered system for private health insurance versus government programs like Medicare and Medicaid. Private insurance generally pays physicians more than government coverage, and Medicare doesn’t use S codes.

Lynn Damitz, a physician and board vice president of health policy and advocacy for the American Society of Plastic Surgeons, said the group supports continuing the S code temporarily or indefinitely. If reimbursements drop, some doctors won’t perform DIEP flaps anymore.

A study published in February found that, of patients who used their own tissue for breast reconstruction, privately insured patients were more likely than publicly insured patients to receive DIEP flap reconstruction.

To Dr. Potter, that shows what will happen if private insurance payments plummet. “If you’re a Medicare provider and you’re not paid to do DIEP flaps, you never tell a patient that it’s an option. You won’t perform it,” Dr. Potter said. “If you take private insurance and all of a sudden your reimbursement rate is cut from $15,000 down to $3,500, you’re not going to do that surgery. And I’m not saying that that’s the right thing to do, but that’s what happens.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The federal government is reconsidering a decision that breast cancer patients, plastic surgeons, and members of Congress have protested would limit women’s options for reconstructive surgery.

On June 1, the Centers for Medicare & Medicaid Services plans to reexamine how doctors are paid for a type of breast reconstruction known as DIEP flap, in which skin, fat, and blood vessels are harvested from a woman’s abdomen to create a new breast.

The procedure offers potential advantages over implants and operations that take muscle from the abdomen. But it’s also more expensive. If patients go outside an insurance network for the operation, it can cost more than $50,000. And, if insurers pay significantly less for the surgery as a result of the government’s decision, some in-network surgeons would stop offering it, a plastic surgeons group has argued.

The DIEP flap controversy, spotlighted by CBS News in January, illustrates arcane and indirect ways the federal government can influence which medical options are available – even to people with private insurance. Often, the answers come down to billing codes – which identify specific medical services on forms doctors submit for reimbursement – and the competing pleas of groups whose interests are riding on them.

Medical coding is the backbone for “how business gets done in medicine,” said Karen Joynt Maddox, MD, MPH, a physician at Washington University in St. Louis who researches health economics and policy.

CMS, the agency overseeing Medicare and Medicaid, maintains a list of codes representing thousands of medical services and products. It regularly evaluates whether to add codes or revise or remove existing ones. In 2022, it decided to eliminate a code that has enabled doctors to collect much more money for DIEP flap operations than for simpler types of breast reconstruction.

In 2006, CMS established an “S” code – S2068 – for what was then a relatively new procedure: breast reconstructions with deep inferior epigastric perforator flap (DIEP flap). S codes temporarily fill gaps in a parallel system of billing codes known as CPT codes, which are maintained by the American Medical Association.

Codes don’t dictate the amounts private insurers pay for medical services; those reimbursements are generally worked out between insurance companies and medical providers. However, using the narrowly targeted S code, doctors and hospitals have been able to distinguish DIEP flap surgeries, which require complex microsurgical skills, from other forms of breast reconstruction that take less time to perform and generally yield lower insurance reimbursements.

CMS announced in 2022 that it planned to eliminate the S code at the end of 2024 – a move some doctors say would slash the amount surgeons are paid. (To be precise, CMS announced it would eliminate a series of three S codes for similar procedures, but some of the more outspoken critics have focused on one of them, S2068.) The agency’s decision is already changing the landscape of reconstructive surgery and creating anxiety for breast cancer patients.

Kate Getz, a single mother in Morton, Ill., learned she had cancer in January at age 30. As she grappled with her diagnosis, it was overwhelming to think about what her body would look like over the long term. She pictured herself getting married one day and wondered “how on earth I would be able to wear a wedding dress with only having one breast left,” she said.

She thought a DIEP flap was her best option and worried about having to undergo repeated surgeries if she got implants instead. Implants generally need to be replaced every 10 years or so. But after she spent more than a month trying to get answers about how her DIEP flap surgery would be covered, Ms. Getz’s insurer, Cigna, informed her it would use a lower-paying CPT code to reimburse her physician, Ms. Getz said. As far as she could see, that would have made it impossible for Ms. Getz to obtain the surgery.

Paying out of pocket was “not even an option.”

“I’m a single mom. We get by, right? But I’m not, not wealthy by any means,” she said.

Cost is not necessarily the only hurdle patients seeking DIEP flaps must overcome. Citing the complexity of the procedure, Ms. Getz said, a local plastic surgeon told her it would be difficult for him to perform. She ended up traveling from Illinois to Texas for the surgery.

The government’s plan to eliminate the three S codes was driven by the Blue Cross Blue Shield Association, a major lobbying organization for health insurance companies. In 2021, the group asked CMS to discontinue the codes, arguing that they were no longer needed because the AMA had updated a CPT code to explicitly include DIEP flap surgery and the related operations, according to a CMS document.

For years, the AMA advised doctors that the CPT code was appropriate for DIEP flap procedures. But after the government’s decision, at least two major insurance companies told doctors they would no longer reimburse them under the higher-paying codes, prompting a backlash.

Physicians and advocacy groups for breast cancer patients, such as the nonprofit organization Susan G. Komen, have argued that many plastic surgeons would stop providing DIEP flap procedures for women with private insurance because they wouldn’t get paid enough.

Lawmakers from both parties have asked the agency to keep the S code, including Rep. Debbie Wasserman Schultz (D-Fla.) and Sen. Amy Klobuchar (D-Minn.), who have had breast cancer, and Sen. Marsha Blackburn (R-Tenn.).

CMS at its June 1 meeting will consider whether to keep the three S codes or delay their expiration.

In a May 30 statement, Blue Cross Blue Shield Association spokesperson Kelly Parsons reiterated the organization’s view that “there is no longer a need to keep the S codes.”

In a profit-driven health care system, there’s a tug of war over reimbursements between providers and insurance companies, often at the expense of patients, said Dr. Joynt Maddox.

“We’re in this sort of constant battle” between hospital chains and insurance companies “about who’s going to wield more power at the bargaining table,” Dr. Joynt Maddox said. “And the clinical piece of that often gets lost, because it’s not often the clinical benefit and the clinical priority and the patient centeredness that’s at the middle of these conversations.”

Elisabeth Potter, MD, a plastic surgeon who specializes in DIEP flap surgeries, decided to perform Ms. Getz’s surgery at whatever price Cigna would pay.

According to Fair Health, a nonprofit that provides information on health care costs, in Austin, Tex. – where Dr. Potter is based – an insurer might pay an in-network doctor $9,323 for the surgery when it’s billed using the CPT code and $18,037 under the S code. Those amounts are not averages; rather, Fair Health estimated that 80% of payment rates are lower than or equal to those amounts.

Dr. Potter said her Cigna reimbursement “is significantly lower.”

Weeks before her May surgery, Ms. Getz received big news – Cigna had reversed itself and would cover her surgery under the S code. It “felt like a real victory,” she said.

But she still fears for other patients.

“I’m still asking these companies to do right by women,” Ms. Getz said. “I’m still asking them to provide the procedures we need to reimburse them at rates where women have access to them regardless of their wealth.”

In a statement, Cigna spokesperson Justine Sessions said the insurer remains “committed to ensuring that our customers have affordable coverage and access to the full range of breast reconstruction procedures and to quality surgeons who perform these complex surgeries.”

Medical costs that health insurers cover generally are passed along to consumers in the form of premiums, deductibles, and other out-of-pocket expenses.

For any type of breast reconstruction, there are benefits, risks, and trade-offs. A 2018 paper published in JAMA Surgery found that women who underwent DIEP flap surgery had higher odds of developing “reoperative complications” within 2 years than those who received artificial implants. However, DIEP flaps had lower odds of infection than implants.

Implants carry risks of additional surgery, pain, rupture, and even an uncommon type of immune system cancer.

Other flap procedures that take muscle from the abdomen can leave women with weakened abdominal walls and increase their risk of developing a hernia.

Academic research shows that insurance reimbursement affects which women can access DIEP flap breast reconstruction, creating a two-tiered system for private health insurance versus government programs like Medicare and Medicaid. Private insurance generally pays physicians more than government coverage, and Medicare doesn’t use S codes.

Lynn Damitz, a physician and board vice president of health policy and advocacy for the American Society of Plastic Surgeons, said the group supports continuing the S code temporarily or indefinitely. If reimbursements drop, some doctors won’t perform DIEP flaps anymore.

A study published in February found that, of patients who used their own tissue for breast reconstruction, privately insured patients were more likely than publicly insured patients to receive DIEP flap reconstruction.

To Dr. Potter, that shows what will happen if private insurance payments plummet. “If you’re a Medicare provider and you’re not paid to do DIEP flaps, you never tell a patient that it’s an option. You won’t perform it,” Dr. Potter said. “If you take private insurance and all of a sudden your reimbursement rate is cut from $15,000 down to $3,500, you’re not going to do that surgery. And I’m not saying that that’s the right thing to do, but that’s what happens.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

An analysis of 61 cities in the United States where employers allow paid work absences for preventive medical services, such as breast and colon cancer screenings, shows that having the option of paid leave does in fact influence one’s decision to have preventive cancer screenings.

“Our results provide evidence for policymakers considering legislative or regulatory solutions to address insufficient screening adherence and highlight an understudied benefit of expanding paid sick leave coverage,” wrote authors who were led by Kevin Callison, PhD, of the Tulane University School of Public Health and Tropical Medicine, New Orleans.

The findings were published earlier this year in the New England Journal of Medicine.

Despite an Affordable Care Act provision eliminating most cost-sharing for cancer screening, the rate for recommended breast and colorectal cancer screening among U.S. adults is lower than 70%. Work commitments, time constraints, and the prospect of lost wages are frequently cited as contributing factors to this underuse of preventive care. Researchers hypothesized that having paid sick leave coverage for the use of preventive services could improve adherence to cancer screening guidelines. With continued failure to pass a bill mandating federal paid sick leave legislation, nearly 30% of the nation’s workforce lacks this coverage. Rates are lower for low-income workers, women, and underserved racial and ethnic groups, the authors write.

Coverage mandates have become politically contentious, as evidenced by the fact that their passage by some states (n = 17), counties (n = 4) and cities (n = 18) has been met by many states (n = 18) passing preemption laws banning municipalities from adopting the laws.

In this study, researchers examined the rate of colorectal and breast cancer screening at 12- and 24-month intervals among people living in one of 61 cities. Before paid sick leave mandates were put in place, cancer screening rates were similar across the board. But once mandates were put in place, cancer screening rates were higher among workers affected by the mandate by 1.31% (95% confidence interval, 0.28-2.34) for 12-month colorectal cancer screening, 1.56% (95% CI, 0.33-2.79) for 24-month colorectal cancer screening, 1.22% (95% CI, −0.20 to 2.64) for 12-month mammography, and 2.07% (95% CI, 0.15-3.99) for 24-month mammography.

“Although these appear to be modest effects, spread across a large population, these indicate a fairly substantial gain in cancer screenings,” Dr. Callison said.

Prior studies showing positive associations between having paid sick leave coverage and whether someone receives cancer screenings are likely confounded by selection bias because they compare workers who have such coverage to those who do not, Dr. Callison and colleagues state in their paper.

“Although the lack of paid sick leave coverage may hinder access to preventive care, current evidence is insufficient to draw meaningful conclusions about its relationship to cancer screening,” the authors write, citing that particularly health conscious workers may take jobs offering sick leave coverage.

Through quasi-experimental design, the present study aimed to overcome such confounding issues. Its analytic sample, using administrative data from the Merative MarketScan Research Databases, encompassed approximately 2.5 million person-specific records per year for the colorectal cancer screening sample. The researchers’ mammography sample included 1.3 million person-specific records per year of the period examined.

The associations cited above translate into relative colorectal cancer screening increases of 8.1% in the 12-month adjusted model and a 5.9% relative increase from the premandate rate in the 24-month adjusted model. The rate was 1.56 percentage points (95% CI, 0.33-2.79) higher in the cities subject to the paid sick leave mandates (a 5.9% relative increase from the premandate rate). For screening mammography in the cities subject to the mandates, the 12-month adjusted 1.22% increase (95% CI, –0.20 to 2.64) represented a 2.5% relative increase from the premandate level. The adjusted 24-month rate increase of 2.07% (95% CI, 0.15-4.00) represented a 3.3% relative increase from premandate rates.

“However, these estimates are averages across all workers in our sample, many of whom likely already had paid sick leave coverage prior to the enactment of a mandate,” Dr. Callison said in the interview. “In fact, in other work related to this project, we estimated that about 28% of private sector workers gain paid sick leave when a mandate is enacted. So then, if we scale our findings by the share of workers actually gaining paid sick leave coverage, our estimates are much larger – a 9%-12% increase in screening mammography and a 21%-29% increase in colorectal cancer screening.”

Dr. Callison and his team are in the process of developing a follow-up proposal that would examine the effects of paid sick leave on downstream outcomes of the cancer care continuum, such as timing from diagnosis to treatment initiation. “We also hope to examine who benefits from these additional screens and what they mean for health equity. Data limitations prevented us from exploring that issue in the current study,” he said.

Dr. Callison had no conflicts associated with this study.

An analysis of 61 cities in the United States where employers allow paid work absences for preventive medical services, such as breast and colon cancer screenings, shows that having the option of paid leave does in fact influence one’s decision to have preventive cancer screenings.

“Our results provide evidence for policymakers considering legislative or regulatory solutions to address insufficient screening adherence and highlight an understudied benefit of expanding paid sick leave coverage,” wrote authors who were led by Kevin Callison, PhD, of the Tulane University School of Public Health and Tropical Medicine, New Orleans.

The findings were published earlier this year in the New England Journal of Medicine.

Despite an Affordable Care Act provision eliminating most cost-sharing for cancer screening, the rate for recommended breast and colorectal cancer screening among U.S. adults is lower than 70%. Work commitments, time constraints, and the prospect of lost wages are frequently cited as contributing factors to this underuse of preventive care. Researchers hypothesized that having paid sick leave coverage for the use of preventive services could improve adherence to cancer screening guidelines. With continued failure to pass a bill mandating federal paid sick leave legislation, nearly 30% of the nation’s workforce lacks this coverage. Rates are lower for low-income workers, women, and underserved racial and ethnic groups, the authors write.

Coverage mandates have become politically contentious, as evidenced by the fact that their passage by some states (n = 17), counties (n = 4) and cities (n = 18) has been met by many states (n = 18) passing preemption laws banning municipalities from adopting the laws.

In this study, researchers examined the rate of colorectal and breast cancer screening at 12- and 24-month intervals among people living in one of 61 cities. Before paid sick leave mandates were put in place, cancer screening rates were similar across the board. But once mandates were put in place, cancer screening rates were higher among workers affected by the mandate by 1.31% (95% confidence interval, 0.28-2.34) for 12-month colorectal cancer screening, 1.56% (95% CI, 0.33-2.79) for 24-month colorectal cancer screening, 1.22% (95% CI, −0.20 to 2.64) for 12-month mammography, and 2.07% (95% CI, 0.15-3.99) for 24-month mammography.

“Although these appear to be modest effects, spread across a large population, these indicate a fairly substantial gain in cancer screenings,” Dr. Callison said.

Prior studies showing positive associations between having paid sick leave coverage and whether someone receives cancer screenings are likely confounded by selection bias because they compare workers who have such coverage to those who do not, Dr. Callison and colleagues state in their paper.

“Although the lack of paid sick leave coverage may hinder access to preventive care, current evidence is insufficient to draw meaningful conclusions about its relationship to cancer screening,” the authors write, citing that particularly health conscious workers may take jobs offering sick leave coverage.

Through quasi-experimental design, the present study aimed to overcome such confounding issues. Its analytic sample, using administrative data from the Merative MarketScan Research Databases, encompassed approximately 2.5 million person-specific records per year for the colorectal cancer screening sample. The researchers’ mammography sample included 1.3 million person-specific records per year of the period examined.

The associations cited above translate into relative colorectal cancer screening increases of 8.1% in the 12-month adjusted model and a 5.9% relative increase from the premandate rate in the 24-month adjusted model. The rate was 1.56 percentage points (95% CI, 0.33-2.79) higher in the cities subject to the paid sick leave mandates (a 5.9% relative increase from the premandate rate). For screening mammography in the cities subject to the mandates, the 12-month adjusted 1.22% increase (95% CI, –0.20 to 2.64) represented a 2.5% relative increase from the premandate level. The adjusted 24-month rate increase of 2.07% (95% CI, 0.15-4.00) represented a 3.3% relative increase from premandate rates.

“However, these estimates are averages across all workers in our sample, many of whom likely already had paid sick leave coverage prior to the enactment of a mandate,” Dr. Callison said in the interview. “In fact, in other work related to this project, we estimated that about 28% of private sector workers gain paid sick leave when a mandate is enacted. So then, if we scale our findings by the share of workers actually gaining paid sick leave coverage, our estimates are much larger – a 9%-12% increase in screening mammography and a 21%-29% increase in colorectal cancer screening.”

Dr. Callison and his team are in the process of developing a follow-up proposal that would examine the effects of paid sick leave on downstream outcomes of the cancer care continuum, such as timing from diagnosis to treatment initiation. “We also hope to examine who benefits from these additional screens and what they mean for health equity. Data limitations prevented us from exploring that issue in the current study,” he said.

Dr. Callison had no conflicts associated with this study.

An analysis of 61 cities in the United States where employers allow paid work absences for preventive medical services, such as breast and colon cancer screenings, shows that having the option of paid leave does in fact influence one’s decision to have preventive cancer screenings.

“Our results provide evidence for policymakers considering legislative or regulatory solutions to address insufficient screening adherence and highlight an understudied benefit of expanding paid sick leave coverage,” wrote authors who were led by Kevin Callison, PhD, of the Tulane University School of Public Health and Tropical Medicine, New Orleans.

The findings were published earlier this year in the New England Journal of Medicine.

Despite an Affordable Care Act provision eliminating most cost-sharing for cancer screening, the rate for recommended breast and colorectal cancer screening among U.S. adults is lower than 70%. Work commitments, time constraints, and the prospect of lost wages are frequently cited as contributing factors to this underuse of preventive care. Researchers hypothesized that having paid sick leave coverage for the use of preventive services could improve adherence to cancer screening guidelines. With continued failure to pass a bill mandating federal paid sick leave legislation, nearly 30% of the nation’s workforce lacks this coverage. Rates are lower for low-income workers, women, and underserved racial and ethnic groups, the authors write.

Coverage mandates have become politically contentious, as evidenced by the fact that their passage by some states (n = 17), counties (n = 4) and cities (n = 18) has been met by many states (n = 18) passing preemption laws banning municipalities from adopting the laws.

In this study, researchers examined the rate of colorectal and breast cancer screening at 12- and 24-month intervals among people living in one of 61 cities. Before paid sick leave mandates were put in place, cancer screening rates were similar across the board. But once mandates were put in place, cancer screening rates were higher among workers affected by the mandate by 1.31% (95% confidence interval, 0.28-2.34) for 12-month colorectal cancer screening, 1.56% (95% CI, 0.33-2.79) for 24-month colorectal cancer screening, 1.22% (95% CI, −0.20 to 2.64) for 12-month mammography, and 2.07% (95% CI, 0.15-3.99) for 24-month mammography.

“Although these appear to be modest effects, spread across a large population, these indicate a fairly substantial gain in cancer screenings,” Dr. Callison said.

Prior studies showing positive associations between having paid sick leave coverage and whether someone receives cancer screenings are likely confounded by selection bias because they compare workers who have such coverage to those who do not, Dr. Callison and colleagues state in their paper.

“Although the lack of paid sick leave coverage may hinder access to preventive care, current evidence is insufficient to draw meaningful conclusions about its relationship to cancer screening,” the authors write, citing that particularly health conscious workers may take jobs offering sick leave coverage.

Through quasi-experimental design, the present study aimed to overcome such confounding issues. Its analytic sample, using administrative data from the Merative MarketScan Research Databases, encompassed approximately 2.5 million person-specific records per year for the colorectal cancer screening sample. The researchers’ mammography sample included 1.3 million person-specific records per year of the period examined.

The associations cited above translate into relative colorectal cancer screening increases of 8.1% in the 12-month adjusted model and a 5.9% relative increase from the premandate rate in the 24-month adjusted model. The rate was 1.56 percentage points (95% CI, 0.33-2.79) higher in the cities subject to the paid sick leave mandates (a 5.9% relative increase from the premandate rate). For screening mammography in the cities subject to the mandates, the 12-month adjusted 1.22% increase (95% CI, –0.20 to 2.64) represented a 2.5% relative increase from the premandate level. The adjusted 24-month rate increase of 2.07% (95% CI, 0.15-4.00) represented a 3.3% relative increase from premandate rates.

“However, these estimates are averages across all workers in our sample, many of whom likely already had paid sick leave coverage prior to the enactment of a mandate,” Dr. Callison said in the interview. “In fact, in other work related to this project, we estimated that about 28% of private sector workers gain paid sick leave when a mandate is enacted. So then, if we scale our findings by the share of workers actually gaining paid sick leave coverage, our estimates are much larger – a 9%-12% increase in screening mammography and a 21%-29% increase in colorectal cancer screening.”

Dr. Callison and his team are in the process of developing a follow-up proposal that would examine the effects of paid sick leave on downstream outcomes of the cancer care continuum, such as timing from diagnosis to treatment initiation. “We also hope to examine who benefits from these additional screens and what they mean for health equity. Data limitations prevented us from exploring that issue in the current study,” he said.

Dr. Callison had no conflicts associated with this study.

Among the patients treated with trastuzumab deruxtecan, median progression-free survival was significantly prolonged compared with the physician's choice treatment group (17.8 vs 6.9 months; hazard ratio 0.36; P < .0001). There were no new safety signals reported for trastuzumab deruxtecan. Of interest, drug-related interstitial lung disease occurred in 10% of patients treated with trastuzumab deruxtecan (including two grade 5 death events) compared with < 1% in the physician's-choice treatment group.

Overall, trastuzumab deruxtecan demonstrated a favorable benefit-risk profile in patients with HER2+ BC previously treated with trastuzumab emtansine. This is the first randomized study to show efficacy with an antibody-drug conjugate after a previous antibody-drug conjugate.

Breast density is a known independent risk factor for BC, furthermore, dense breast tissue can make identifying BC on screening mammograms more challenging. The nested case-control cohort study by Jiang and colleagues observed women with no history of any cancer for 10 years, with screening mammograms every 1-2 years. Subsequently, 289 women who developed BC were identified and analyzed along with 658 matched control individuals. BC risk factors were also collected via questionnaires at the time of enrollment. Of note, the BC cases cohort had an overall higher mean body mass index, a higher percentage of Black women, and of women with a family history of BC. The results showed that though women's breast density decreased over time in both cases and controls, the rate of change in breast density was significantly slower in the breast that later developed cancer compared with the cancer-free breast in control individuals (estimate 0.027; P = .04). Enhancing screening modalities to enable assessing for longitudinal changes in breast density may provide an additional tool for evaluating the risk for BC.

Reducing the late BC recurrence risk beyond 5 years is a significant issue in patients with hormone receptor–positive (HR+) BC. This prospective, randomized, phase 3, AERAS trial included 1593 postmenopausal women with HR+ early-stage invasive BC who were disease-free at 5 years after postoperative endocrine therapy. Patients were randomly assigned 1:1 to stop or continue receiving anastrozole for an additional 5 years. Results showed that continuation of anastrozole treatment for an additional 5 years significantly improved 5-year disease-free survival (DFS) (hazard ratio 0.61; 95% CI 0.46-0.82; P < .0010). Furthermore, extended anastrozole treatment reduced the incidence of local recurrence and second primary cancers. However, there was no significant difference in distant DFS. The incidence of grade 3 or higher adverse events was < 1% in both groups, although menopausal or bone-related all-grade adverse events were more frequent among patients in the group that continued with anastrozole, as expected. Results from this study help inform the risks and benefits of extending hormone therapy beyond 5 years.

The RxPONDER trial comparing endocrine therapy (ET) alone to chemotherapy plus endocrine therapy (CET) in patients with one to three positive axillary lymph nodes and recurrence score (RS) ≤ 25 showed that CET did not improve survival outcomes compared with ET alone in postmenopausal women with HR+/HER2- BC. This retrospective cohort study of real-world data from the National Cancer Database included 28,427 women with stage I-III HR+/HER2- BC and one to three positive axillary lymph nodes, of which 26.3% and 73.7% of patients received CET and ET, respectively. Results showed that in patients with RS of 20-25, CET was associated with a significant improvement in overall survival compared with ET alone, in both premenopausal (age ≤ 50 years: hazard ratio 0.334, P = .002) and postmenopausal patients (age > 50 years: hazard ratio 0.521, P = .019). Though these results are inconsistent with the RxPONDER trial results regarding the postmenopausal cohort, they do raise an important finding that is supported by prior published data.¹ More studies are needed to validate these findings. At this time, guidelines recommend omitting chemotherapy in patients with HR+/HER2- BC, one to three positive axillary lymph nodes, and an RS of 20-25 per RxPONDER.

Additional Reference

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. doi: 10.1016/S0140-6736(11)61625-5

Among the patients treated with trastuzumab deruxtecan, median progression-free survival was significantly prolonged compared with the physician's choice treatment group (17.8 vs 6.9 months; hazard ratio 0.36; P < .0001). There were no new safety signals reported for trastuzumab deruxtecan. Of interest, drug-related interstitial lung disease occurred in 10% of patients treated with trastuzumab deruxtecan (including two grade 5 death events) compared with < 1% in the physician's-choice treatment group.

Overall, trastuzumab deruxtecan demonstrated a favorable benefit-risk profile in patients with HER2+ BC previously treated with trastuzumab emtansine. This is the first randomized study to show efficacy with an antibody-drug conjugate after a previous antibody-drug conjugate.

Breast density is a known independent risk factor for BC, furthermore, dense breast tissue can make identifying BC on screening mammograms more challenging. The nested case-control cohort study by Jiang and colleagues observed women with no history of any cancer for 10 years, with screening mammograms every 1-2 years. Subsequently, 289 women who developed BC were identified and analyzed along with 658 matched control individuals. BC risk factors were also collected via questionnaires at the time of enrollment. Of note, the BC cases cohort had an overall higher mean body mass index, a higher percentage of Black women, and of women with a family history of BC. The results showed that though women's breast density decreased over time in both cases and controls, the rate of change in breast density was significantly slower in the breast that later developed cancer compared with the cancer-free breast in control individuals (estimate 0.027; P = .04). Enhancing screening modalities to enable assessing for longitudinal changes in breast density may provide an additional tool for evaluating the risk for BC.

Reducing the late BC recurrence risk beyond 5 years is a significant issue in patients with hormone receptor–positive (HR+) BC. This prospective, randomized, phase 3, AERAS trial included 1593 postmenopausal women with HR+ early-stage invasive BC who were disease-free at 5 years after postoperative endocrine therapy. Patients were randomly assigned 1:1 to stop or continue receiving anastrozole for an additional 5 years. Results showed that continuation of anastrozole treatment for an additional 5 years significantly improved 5-year disease-free survival (DFS) (hazard ratio 0.61; 95% CI 0.46-0.82; P < .0010). Furthermore, extended anastrozole treatment reduced the incidence of local recurrence and second primary cancers. However, there was no significant difference in distant DFS. The incidence of grade 3 or higher adverse events was < 1% in both groups, although menopausal or bone-related all-grade adverse events were more frequent among patients in the group that continued with anastrozole, as expected. Results from this study help inform the risks and benefits of extending hormone therapy beyond 5 years.

The RxPONDER trial comparing endocrine therapy (ET) alone to chemotherapy plus endocrine therapy (CET) in patients with one to three positive axillary lymph nodes and recurrence score (RS) ≤ 25 showed that CET did not improve survival outcomes compared with ET alone in postmenopausal women with HR+/HER2- BC. This retrospective cohort study of real-world data from the National Cancer Database included 28,427 women with stage I-III HR+/HER2- BC and one to three positive axillary lymph nodes, of which 26.3% and 73.7% of patients received CET and ET, respectively. Results showed that in patients with RS of 20-25, CET was associated with a significant improvement in overall survival compared with ET alone, in both premenopausal (age ≤ 50 years: hazard ratio 0.334, P = .002) and postmenopausal patients (age > 50 years: hazard ratio 0.521, P = .019). Though these results are inconsistent with the RxPONDER trial results regarding the postmenopausal cohort, they do raise an important finding that is supported by prior published data.¹ More studies are needed to validate these findings. At this time, guidelines recommend omitting chemotherapy in patients with HR+/HER2- BC, one to three positive axillary lymph nodes, and an RS of 20-25 per RxPONDER.

Additional Reference

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. doi: 10.1016/S0140-6736(11)61625-5

Among the patients treated with trastuzumab deruxtecan, median progression-free survival was significantly prolonged compared with the physician's choice treatment group (17.8 vs 6.9 months; hazard ratio 0.36; P < .0001). There were no new safety signals reported for trastuzumab deruxtecan. Of interest, drug-related interstitial lung disease occurred in 10% of patients treated with trastuzumab deruxtecan (including two grade 5 death events) compared with < 1% in the physician's-choice treatment group.

Overall, trastuzumab deruxtecan demonstrated a favorable benefit-risk profile in patients with HER2+ BC previously treated with trastuzumab emtansine. This is the first randomized study to show efficacy with an antibody-drug conjugate after a previous antibody-drug conjugate.

Breast density is a known independent risk factor for BC, furthermore, dense breast tissue can make identifying BC on screening mammograms more challenging. The nested case-control cohort study by Jiang and colleagues observed women with no history of any cancer for 10 years, with screening mammograms every 1-2 years. Subsequently, 289 women who developed BC were identified and analyzed along with 658 matched control individuals. BC risk factors were also collected via questionnaires at the time of enrollment. Of note, the BC cases cohort had an overall higher mean body mass index, a higher percentage of Black women, and of women with a family history of BC. The results showed that though women's breast density decreased over time in both cases and controls, the rate of change in breast density was significantly slower in the breast that later developed cancer compared with the cancer-free breast in control individuals (estimate 0.027; P = .04). Enhancing screening modalities to enable assessing for longitudinal changes in breast density may provide an additional tool for evaluating the risk for BC.

Reducing the late BC recurrence risk beyond 5 years is a significant issue in patients with hormone receptor–positive (HR+) BC. This prospective, randomized, phase 3, AERAS trial included 1593 postmenopausal women with HR+ early-stage invasive BC who were disease-free at 5 years after postoperative endocrine therapy. Patients were randomly assigned 1:1 to stop or continue receiving anastrozole for an additional 5 years. Results showed that continuation of anastrozole treatment for an additional 5 years significantly improved 5-year disease-free survival (DFS) (hazard ratio 0.61; 95% CI 0.46-0.82; P < .0010). Furthermore, extended anastrozole treatment reduced the incidence of local recurrence and second primary cancers. However, there was no significant difference in distant DFS. The incidence of grade 3 or higher adverse events was < 1% in both groups, although menopausal or bone-related all-grade adverse events were more frequent among patients in the group that continued with anastrozole, as expected. Results from this study help inform the risks and benefits of extending hormone therapy beyond 5 years.

The RxPONDER trial comparing endocrine therapy (ET) alone to chemotherapy plus endocrine therapy (CET) in patients with one to three positive axillary lymph nodes and recurrence score (RS) ≤ 25 showed that CET did not improve survival outcomes compared with ET alone in postmenopausal women with HR+/HER2- BC. This retrospective cohort study of real-world data from the National Cancer Database included 28,427 women with stage I-III HR+/HER2- BC and one to three positive axillary lymph nodes, of which 26.3% and 73.7% of patients received CET and ET, respectively. Results showed that in patients with RS of 20-25, CET was associated with a significant improvement in overall survival compared with ET alone, in both premenopausal (age ≤ 50 years: hazard ratio 0.334, P = .002) and postmenopausal patients (age > 50 years: hazard ratio 0.521, P = .019). Though these results are inconsistent with the RxPONDER trial results regarding the postmenopausal cohort, they do raise an important finding that is supported by prior published data.¹ More studies are needed to validate these findings. At this time, guidelines recommend omitting chemotherapy in patients with HR+/HER2- BC, one to three positive axillary lymph nodes, and an RS of 20-25 per RxPONDER.

Additional Reference

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. doi: 10.1016/S0140-6736(11)61625-5

Detection of circulating tumor DNA was significantly associated with worse rates of disease-free and overall survival in patients with stage I-III breast cancer, a new meta-analysis and systematic review found.

“Circulating tumor DNA (ctDNA) has been extensively studied as a prognostic biomarker in early breast cancer. However, there is a significant heterogeneity in the study results, which is probably related to the fact that each individual study included different patient populations, collected blood at different time points, and used different methods (assays) for ctDNA analysis,” said Guilherme Nader Marta, MD, of the Institut Jules Bordet, Anderlecht, Belgium, in an interview.

“The aim of our study was to summarize the available evidence that has been presented so far on this topic by performing a systematic review and meta-analysis including studies that reported the association between ctDNA detection and long-term outcomes,” said Dr. Nader Marta, who coauthored the new research, which was presented as a poster (Poster 26P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Methods and results

The authors identified 57 studies including data from 5,729 individuals with early breast cancer. The 44.5% for whom stages were reported consisted of 18.3% with stage I disease, 60.0% with stage II, and 21.5% with stage III. Patients’ ctDNA collection was divided into three groups: baseline, after neoadjuvant therapy (End-of-NAT), and during follow-up care; ctDNA assays were classified as tumor-informed or non–tumor-informed.

The detection of ctDNA at any time point during diagnosis and treatment was associated with worse disease-free survival (DFS) and overall survival (OS), compared with no ctDNA. The association was stronger in tumor-informed assays, the researchers said.

For disease-free survival, the overall multivariate hazard ratios were 2.5, 5.5, and 7.2 for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

For overall survival, the overall multivariate hazard ratios were 3.0, 12.9, and 5.6, for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

The pooled hazard ratios were numerically higher for both DFS and OS when ctDNA was detected at either End-of-NAT or follow-up.

In addition, detection of ctDNA was associated with a high degree of specificity (from 0.7 to 1.0) for breast cancer relapse; sensitivity ranged from 0.31 to 1.0, the researchers noted. The mean lead time from ctDNA detection to breast cancer recurrence in these cases was approximately 10 months.
 

Results show ctDNA detection is associated with worse survival

“Our study results demonstrate that ctDNA detection is associated with worse disease-free survival and overall survival in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays,” Dr. Nader Marta said in an interview.

“As next steps, we need to build on this evidence to bring the potential benefits of this powerful prognostic tool to our patients,” said Dr. Nader Marta. “Ongoing studies exploring different management strategies based on serial ctDNA assessments will help us understand the exact role of this technology in our clinical practice.”

The study received no outside funding. Dr. Nader Marta disclosed relationships with companies including Roche and Bayer.
 

Detection of circulating tumor DNA was significantly associated with worse rates of disease-free and overall survival in patients with stage I-III breast cancer, a new meta-analysis and systematic review found.

“Circulating tumor DNA (ctDNA) has been extensively studied as a prognostic biomarker in early breast cancer. However, there is a significant heterogeneity in the study results, which is probably related to the fact that each individual study included different patient populations, collected blood at different time points, and used different methods (assays) for ctDNA analysis,” said Guilherme Nader Marta, MD, of the Institut Jules Bordet, Anderlecht, Belgium, in an interview.

“The aim of our study was to summarize the available evidence that has been presented so far on this topic by performing a systematic review and meta-analysis including studies that reported the association between ctDNA detection and long-term outcomes,” said Dr. Nader Marta, who coauthored the new research, which was presented as a poster (Poster 26P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Methods and results

The authors identified 57 studies including data from 5,729 individuals with early breast cancer. The 44.5% for whom stages were reported consisted of 18.3% with stage I disease, 60.0% with stage II, and 21.5% with stage III. Patients’ ctDNA collection was divided into three groups: baseline, after neoadjuvant therapy (End-of-NAT), and during follow-up care; ctDNA assays were classified as tumor-informed or non–tumor-informed.

The detection of ctDNA at any time point during diagnosis and treatment was associated with worse disease-free survival (DFS) and overall survival (OS), compared with no ctDNA. The association was stronger in tumor-informed assays, the researchers said.

For disease-free survival, the overall multivariate hazard ratios were 2.5, 5.5, and 7.2 for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

For overall survival, the overall multivariate hazard ratios were 3.0, 12.9, and 5.6, for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

The pooled hazard ratios were numerically higher for both DFS and OS when ctDNA was detected at either End-of-NAT or follow-up.

In addition, detection of ctDNA was associated with a high degree of specificity (from 0.7 to 1.0) for breast cancer relapse; sensitivity ranged from 0.31 to 1.0, the researchers noted. The mean lead time from ctDNA detection to breast cancer recurrence in these cases was approximately 10 months.
 

Results show ctDNA detection is associated with worse survival

“Our study results demonstrate that ctDNA detection is associated with worse disease-free survival and overall survival in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays,” Dr. Nader Marta said in an interview.

“As next steps, we need to build on this evidence to bring the potential benefits of this powerful prognostic tool to our patients,” said Dr. Nader Marta. “Ongoing studies exploring different management strategies based on serial ctDNA assessments will help us understand the exact role of this technology in our clinical practice.”

The study received no outside funding. Dr. Nader Marta disclosed relationships with companies including Roche and Bayer.
 

Detection of circulating tumor DNA was significantly associated with worse rates of disease-free and overall survival in patients with stage I-III breast cancer, a new meta-analysis and systematic review found.

“Circulating tumor DNA (ctDNA) has been extensively studied as a prognostic biomarker in early breast cancer. However, there is a significant heterogeneity in the study results, which is probably related to the fact that each individual study included different patient populations, collected blood at different time points, and used different methods (assays) for ctDNA analysis,” said Guilherme Nader Marta, MD, of the Institut Jules Bordet, Anderlecht, Belgium, in an interview.

“The aim of our study was to summarize the available evidence that has been presented so far on this topic by performing a systematic review and meta-analysis including studies that reported the association between ctDNA detection and long-term outcomes,” said Dr. Nader Marta, who coauthored the new research, which was presented as a poster (Poster 26P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Methods and results

The authors identified 57 studies including data from 5,729 individuals with early breast cancer. The 44.5% for whom stages were reported consisted of 18.3% with stage I disease, 60.0% with stage II, and 21.5% with stage III. Patients’ ctDNA collection was divided into three groups: baseline, after neoadjuvant therapy (End-of-NAT), and during follow-up care; ctDNA assays were classified as tumor-informed or non–tumor-informed.

The detection of ctDNA at any time point during diagnosis and treatment was associated with worse disease-free survival (DFS) and overall survival (OS), compared with no ctDNA. The association was stronger in tumor-informed assays, the researchers said.

For disease-free survival, the overall multivariate hazard ratios were 2.5, 5.5, and 7.2 for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

For overall survival, the overall multivariate hazard ratios were 3.0, 12.9, and 5.6, for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

The pooled hazard ratios were numerically higher for both DFS and OS when ctDNA was detected at either End-of-NAT or follow-up.

In addition, detection of ctDNA was associated with a high degree of specificity (from 0.7 to 1.0) for breast cancer relapse; sensitivity ranged from 0.31 to 1.0, the researchers noted. The mean lead time from ctDNA detection to breast cancer recurrence in these cases was approximately 10 months.
 

Results show ctDNA detection is associated with worse survival

“Our study results demonstrate that ctDNA detection is associated with worse disease-free survival and overall survival in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays,” Dr. Nader Marta said in an interview.

“As next steps, we need to build on this evidence to bring the potential benefits of this powerful prognostic tool to our patients,” said Dr. Nader Marta. “Ongoing studies exploring different management strategies based on serial ctDNA assessments will help us understand the exact role of this technology in our clinical practice.”

The study received no outside funding. Dr. Nader Marta disclosed relationships with companies including Roche and Bayer.
 

A new study finds that racial disparities in male breast cancer are persisting in the United States.

From 2000 to 2019, Black men were diagnosed at later ages than White males (median ages, 69 and 63 years, respectively) and were more likely to die from the disease (22.4% vs. 16.8%, respectively). Male breast cancer (MBC) was more likely to kill Black men in rural vs. urban areas (hazard ratio = 1.4; 95% confidence interval, 1.0-2.1; P less than .05). Among White males, in contrast, there was no difference on that front, according to the research, which was presented in a poster (Abstract No. 87P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

It’s not clear why the disparities exist, said lead author Lekha Yadukumar, MBBS, an internal medicine resident at the Wright Center for Graduate Medical Education in Scranton, Penn., in an interview.

“Several potential factors may contribute to the higher rate of breast cancer diagnosis in older [Black] men, including the pathology of the disease, limited awareness about breast cancer, and potential barriers to accessibility,” she said. “The increased mortality among [Black men] may be linked to variations in tumor pathology and molecular biology. Social factors may also potentially impact survival rates, including [having] limited access to health care in rural areas and inadequate social support.”

Male breast cancer is rare, accounting for less than 1% of all breast cancer cases in the United States, according to the Breast Cancer Research Foundation. An estimated 2,700 men are diagnosed each year, and about 530 will die. Previous research has suggested Black men have worse outcomes than White men, but the data covered earlier years than the new study.
 

Methods and results

Dr. Yadukumar and colleagues retrospectively analyzed statistics from the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary male breast cancer from 2000 to 2019 (n = 8,373; Black men, 1,111 [13.26%]; White men, 6,817 [81.41%]).

Median income didn’t affect mortality, whereas men in both racial groups were less likely to die if they were married vs. single/divorced (hazard ratio = 0.6; P less than .05).

Other studies have shown that “[Black American] men diagnosed with breast cancer experience longer time intervals before receiving treatment, encounter more severe disease manifestations, and exhibit lower rates of survivorship,” Dr. Yadukumar said. “Despite these findings, there remains a scarcity of genetic studies aimed at comprehending the underlying causes of these disparities. Moreover, there is a dearth of research investigating other factors that may influence survival outcomes among men with breast cancer.”
 

Findings reflect the disparities in female breast cancer

In an interview, Duke University, Durham, N.C., oncologist Arif Kamal, MD, MBA, MHS, the chief patient officer at the American Cancer Society, said the study is impressive since the number of patients is large for a rare cancer and the population is diverse. Plus, the findings reflect the disparities in female breast cancer, he noted.

“We know that Black women’s mortality is worse vs. White women in breast cancer, and we believe that most of that has nothing to do with cancer screening,” said Dr. Kamal, who was not involved in the new study. “When the clock starts from diagnosis onwards, you start to see less introduction to clinical trials and standard care medications and more time to treatment, surgery, and radiation,” he said.

“You see similar disparities as related to mortality in Black vs. White men,” he noted.

The new findings about higher death rates for Black men, especially in rural areas, suggest that “distance matters, and race matters,” he said. In rural areas, it can be hard to access pathologists, radiologists, and surgeons with more experience with breast cancer, he said.

But, he noted, the study finds that income doesn’t appear to be a factor.

In the big picture, he said, the results suggest that when it comes to barriers to better outcomes, “things that are systemic don’t make exceptions because you are a man vs. a woman.”

No study funding was reported. The study authors and Dr. Kamal have no relevant financial disclosures.
 

A new study finds that racial disparities in male breast cancer are persisting in the United States.

From 2000 to 2019, Black men were diagnosed at later ages than White males (median ages, 69 and 63 years, respectively) and were more likely to die from the disease (22.4% vs. 16.8%, respectively). Male breast cancer (MBC) was more likely to kill Black men in rural vs. urban areas (hazard ratio = 1.4; 95% confidence interval, 1.0-2.1; P less than .05). Among White males, in contrast, there was no difference on that front, according to the research, which was presented in a poster (Abstract No. 87P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

It’s not clear why the disparities exist, said lead author Lekha Yadukumar, MBBS, an internal medicine resident at the Wright Center for Graduate Medical Education in Scranton, Penn., in an interview.

“Several potential factors may contribute to the higher rate of breast cancer diagnosis in older [Black] men, including the pathology of the disease, limited awareness about breast cancer, and potential barriers to accessibility,” she said. “The increased mortality among [Black men] may be linked to variations in tumor pathology and molecular biology. Social factors may also potentially impact survival rates, including [having] limited access to health care in rural areas and inadequate social support.”

Male breast cancer is rare, accounting for less than 1% of all breast cancer cases in the United States, according to the Breast Cancer Research Foundation. An estimated 2,700 men are diagnosed each year, and about 530 will die. Previous research has suggested Black men have worse outcomes than White men, but the data covered earlier years than the new study.
 

Methods and results

Dr. Yadukumar and colleagues retrospectively analyzed statistics from the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary male breast cancer from 2000 to 2019 (n = 8,373; Black men, 1,111 [13.26%]; White men, 6,817 [81.41%]).

Median income didn’t affect mortality, whereas men in both racial groups were less likely to die if they were married vs. single/divorced (hazard ratio = 0.6; P less than .05).

Other studies have shown that “[Black American] men diagnosed with breast cancer experience longer time intervals before receiving treatment, encounter more severe disease manifestations, and exhibit lower rates of survivorship,” Dr. Yadukumar said. “Despite these findings, there remains a scarcity of genetic studies aimed at comprehending the underlying causes of these disparities. Moreover, there is a dearth of research investigating other factors that may influence survival outcomes among men with breast cancer.”
 

Findings reflect the disparities in female breast cancer

In an interview, Duke University, Durham, N.C., oncologist Arif Kamal, MD, MBA, MHS, the chief patient officer at the American Cancer Society, said the study is impressive since the number of patients is large for a rare cancer and the population is diverse. Plus, the findings reflect the disparities in female breast cancer, he noted.

“We know that Black women’s mortality is worse vs. White women in breast cancer, and we believe that most of that has nothing to do with cancer screening,” said Dr. Kamal, who was not involved in the new study. “When the clock starts from diagnosis onwards, you start to see less introduction to clinical trials and standard care medications and more time to treatment, surgery, and radiation,” he said.

“You see similar disparities as related to mortality in Black vs. White men,” he noted.

The new findings about higher death rates for Black men, especially in rural areas, suggest that “distance matters, and race matters,” he said. In rural areas, it can be hard to access pathologists, radiologists, and surgeons with more experience with breast cancer, he said.

But, he noted, the study finds that income doesn’t appear to be a factor.

In the big picture, he said, the results suggest that when it comes to barriers to better outcomes, “things that are systemic don’t make exceptions because you are a man vs. a woman.”

No study funding was reported. The study authors and Dr. Kamal have no relevant financial disclosures.
 

A new study finds that racial disparities in male breast cancer are persisting in the United States.

From 2000 to 2019, Black men were diagnosed at later ages than White males (median ages, 69 and 63 years, respectively) and were more likely to die from the disease (22.4% vs. 16.8%, respectively). Male breast cancer (MBC) was more likely to kill Black men in rural vs. urban areas (hazard ratio = 1.4; 95% confidence interval, 1.0-2.1; P less than .05). Among White males, in contrast, there was no difference on that front, according to the research, which was presented in a poster (Abstract No. 87P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

It’s not clear why the disparities exist, said lead author Lekha Yadukumar, MBBS, an internal medicine resident at the Wright Center for Graduate Medical Education in Scranton, Penn., in an interview.

“Several potential factors may contribute to the higher rate of breast cancer diagnosis in older [Black] men, including the pathology of the disease, limited awareness about breast cancer, and potential barriers to accessibility,” she said. “The increased mortality among [Black men] may be linked to variations in tumor pathology and molecular biology. Social factors may also potentially impact survival rates, including [having] limited access to health care in rural areas and inadequate social support.”

Male breast cancer is rare, accounting for less than 1% of all breast cancer cases in the United States, according to the Breast Cancer Research Foundation. An estimated 2,700 men are diagnosed each year, and about 530 will die. Previous research has suggested Black men have worse outcomes than White men, but the data covered earlier years than the new study.
 

Methods and results

Dr. Yadukumar and colleagues retrospectively analyzed statistics from the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary male breast cancer from 2000 to 2019 (n = 8,373; Black men, 1,111 [13.26%]; White men, 6,817 [81.41%]).

Median income didn’t affect mortality, whereas men in both racial groups were less likely to die if they were married vs. single/divorced (hazard ratio = 0.6; P less than .05).

Other studies have shown that “[Black American] men diagnosed with breast cancer experience longer time intervals before receiving treatment, encounter more severe disease manifestations, and exhibit lower rates of survivorship,” Dr. Yadukumar said. “Despite these findings, there remains a scarcity of genetic studies aimed at comprehending the underlying causes of these disparities. Moreover, there is a dearth of research investigating other factors that may influence survival outcomes among men with breast cancer.”
 

Findings reflect the disparities in female breast cancer

In an interview, Duke University, Durham, N.C., oncologist Arif Kamal, MD, MBA, MHS, the chief patient officer at the American Cancer Society, said the study is impressive since the number of patients is large for a rare cancer and the population is diverse. Plus, the findings reflect the disparities in female breast cancer, he noted.

“We know that Black women’s mortality is worse vs. White women in breast cancer, and we believe that most of that has nothing to do with cancer screening,” said Dr. Kamal, who was not involved in the new study. “When the clock starts from diagnosis onwards, you start to see less introduction to clinical trials and standard care medications and more time to treatment, surgery, and radiation,” he said.

“You see similar disparities as related to mortality in Black vs. White men,” he noted.

The new findings about higher death rates for Black men, especially in rural areas, suggest that “distance matters, and race matters,” he said. In rural areas, it can be hard to access pathologists, radiologists, and surgeons with more experience with breast cancer, he said.

But, he noted, the study finds that income doesn’t appear to be a factor.

In the big picture, he said, the results suggest that when it comes to barriers to better outcomes, “things that are systemic don’t make exceptions because you are a man vs. a woman.”

No study funding was reported. The study authors and Dr. Kamal have no relevant financial disclosures.
 

The advantages of neoadjuvant therapy (NAT), including the downstaging of the primary tumor/nodal burden and assessment of the tumor biology via response to chemotherapy, can have prognostic and therapeutic implications in the adjuvant setting. Additionally, trials in the neoadjuvant space allow rapid assessment of new agents that can help patients gain access to these therapies in an expedited fashion. Three-year outcomes from the neoadjuvant I-SPY2 trial have shown that achievement of pathologic complete response (pCR) after NAT is associated with an approximately 80% reduction in recurrence rate, regardless of molecular subtype or treatment regimen (including various novel therapy combinations).³ An analysis of individual data from 3710 patients with human epidermal growth factor receptor 2 (HER2)–positive early BC from 11 neoadjuvant trials evaluated additional prognostic factors to better characterize pCR (van Mackelenbergh et al). A total of 1497 patients (40%) had pCR, and these patients had improved event-free survival (hazard ratio 0.39; P < .001) and overall survival (hazard ratio 0.32 P < .001) compared to those with residual disease after NAT. Among patients who had pCR, tumor size at presentation (cT1-2 vs cT3-4) and nodal status (cN0 vs cN+) were independent prognostic factors for event-free survival (hazard ratio 0.67 [P = .007] and 0.72 [P = .039], respectively). These data support the role of pCR as an indicator of outcome post-NAT and, furthermore, identify additional features beyond pCR that can affect recurrence risk. It is valuable to take these other factors into account when considering patients for adjuvant therapies, even in the context of pCR.

Advances in detection modalities and treatments have led to improved survival after BC diagnosis, and as a result, more women in the survivorship setting are experiencing side effects that affect quality of life. The prevalence of sexual dysfunction is variable, perhaps owing to how this variable is defined and reported, and includes symptoms of low libido, dyspareunia, vaginal dryness, and anorgasmia.⁴ Chang and colleagues performed a population-based study evaluating sexual dysfunction among a cohort of 19,709 BC survivors ≥ 18 years of age from the Utah Cancer Registry and 93,389 cancer-free women matched by age and birth state from the general population. BC survivors had a higher risk for sexual dysfunction (hazard ratio 1.60; 95% CI 1.51-1.70) compared with the general population, and this effect was more prominent within 1-5 years after diagnosis (hazard ratio 2.05; 95% CI 1.89-2.22) and in those < 50 years of age (hazard ratio 3.05; 95% CI 2.65-3.51). Furthermore, BC survivors who received chemotherapy and ET had an increased risk for sexual dysfunction (hazard ratio 1.16 and 1.46, respectively). These findings underscore the importance of recognition and communication regarding survivorship issues, such as sexual health, which can affect medication adherence, quality of life, and outcomes for patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: a systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.200535
2. Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer. 2022;173:113-12 doi: 10.1016/j.ejca.20206.048
3. I-SPY2 Trial Consortium. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6:1355-1362. doi: 10.1001/jamaoncol.2020.2535
4. Panjari M, Bell RJ, Davis SR. Sexual function after breast cancer. J Sex Med. 2011;8:294-302. doi: 10.1111/j.1743-6109.2010.0203x

The advantages of neoadjuvant therapy (NAT), including the downstaging of the primary tumor/nodal burden and assessment of the tumor biology via response to chemotherapy, can have prognostic and therapeutic implications in the adjuvant setting. Additionally, trials in the neoadjuvant space allow rapid assessment of new agents that can help patients gain access to these therapies in an expedited fashion. Three-year outcomes from the neoadjuvant I-SPY2 trial have shown that achievement of pathologic complete response (pCR) after NAT is associated with an approximately 80% reduction in recurrence rate, regardless of molecular subtype or treatment regimen (including various novel therapy combinations).³ An analysis of individual data from 3710 patients with human epidermal growth factor receptor 2 (HER2)–positive early BC from 11 neoadjuvant trials evaluated additional prognostic factors to better characterize pCR (van Mackelenbergh et al). A total of 1497 patients (40%) had pCR, and these patients had improved event-free survival (hazard ratio 0.39; P < .001) and overall survival (hazard ratio 0.32 P < .001) compared to those with residual disease after NAT. Among patients who had pCR, tumor size at presentation (cT1-2 vs cT3-4) and nodal status (cN0 vs cN+) were independent prognostic factors for event-free survival (hazard ratio 0.67 [P = .007] and 0.72 [P = .039], respectively). These data support the role of pCR as an indicator of outcome post-NAT and, furthermore, identify additional features beyond pCR that can affect recurrence risk. It is valuable to take these other factors into account when considering patients for adjuvant therapies, even in the context of pCR.

Advances in detection modalities and treatments have led to improved survival after BC diagnosis, and as a result, more women in the survivorship setting are experiencing side effects that affect quality of life. The prevalence of sexual dysfunction is variable, perhaps owing to how this variable is defined and reported, and includes symptoms of low libido, dyspareunia, vaginal dryness, and anorgasmia.⁴ Chang and colleagues performed a population-based study evaluating sexual dysfunction among a cohort of 19,709 BC survivors ≥ 18 years of age from the Utah Cancer Registry and 93,389 cancer-free women matched by age and birth state from the general population. BC survivors had a higher risk for sexual dysfunction (hazard ratio 1.60; 95% CI 1.51-1.70) compared with the general population, and this effect was more prominent within 1-5 years after diagnosis (hazard ratio 2.05; 95% CI 1.89-2.22) and in those < 50 years of age (hazard ratio 3.05; 95% CI 2.65-3.51). Furthermore, BC survivors who received chemotherapy and ET had an increased risk for sexual dysfunction (hazard ratio 1.16 and 1.46, respectively). These findings underscore the importance of recognition and communication regarding survivorship issues, such as sexual health, which can affect medication adherence, quality of life, and outcomes for patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: a systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.200535
2. Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer. 2022;173:113-12 doi: 10.1016/j.ejca.20206.048
3. I-SPY2 Trial Consortium. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6:1355-1362. doi: 10.1001/jamaoncol.2020.2535
4. Panjari M, Bell RJ, Davis SR. Sexual function after breast cancer. J Sex Med. 2011;8:294-302. doi: 10.1111/j.1743-6109.2010.0203x

The advantages of neoadjuvant therapy (NAT), including the downstaging of the primary tumor/nodal burden and assessment of the tumor biology via response to chemotherapy, can have prognostic and therapeutic implications in the adjuvant setting. Additionally, trials in the neoadjuvant space allow rapid assessment of new agents that can help patients gain access to these therapies in an expedited fashion. Three-year outcomes from the neoadjuvant I-SPY2 trial have shown that achievement of pathologic complete response (pCR) after NAT is associated with an approximately 80% reduction in recurrence rate, regardless of molecular subtype or treatment regimen (including various novel therapy combinations).³ An analysis of individual data from 3710 patients with human epidermal growth factor receptor 2 (HER2)–positive early BC from 11 neoadjuvant trials evaluated additional prognostic factors to better characterize pCR (van Mackelenbergh et al). A total of 1497 patients (40%) had pCR, and these patients had improved event-free survival (hazard ratio 0.39; P < .001) and overall survival (hazard ratio 0.32 P < .001) compared to those with residual disease after NAT. Among patients who had pCR, tumor size at presentation (cT1-2 vs cT3-4) and nodal status (cN0 vs cN+) were independent prognostic factors for event-free survival (hazard ratio 0.67 [P = .007] and 0.72 [P = .039], respectively). These data support the role of pCR as an indicator of outcome post-NAT and, furthermore, identify additional features beyond pCR that can affect recurrence risk. It is valuable to take these other factors into account when considering patients for adjuvant therapies, even in the context of pCR.

Advances in detection modalities and treatments have led to improved survival after BC diagnosis, and as a result, more women in the survivorship setting are experiencing side effects that affect quality of life. The prevalence of sexual dysfunction is variable, perhaps owing to how this variable is defined and reported, and includes symptoms of low libido, dyspareunia, vaginal dryness, and anorgasmia.⁴ Chang and colleagues performed a population-based study evaluating sexual dysfunction among a cohort of 19,709 BC survivors ≥ 18 years of age from the Utah Cancer Registry and 93,389 cancer-free women matched by age and birth state from the general population. BC survivors had a higher risk for sexual dysfunction (hazard ratio 1.60; 95% CI 1.51-1.70) compared with the general population, and this effect was more prominent within 1-5 years after diagnosis (hazard ratio 2.05; 95% CI 1.89-2.22) and in those < 50 years of age (hazard ratio 3.05; 95% CI 2.65-3.51). Furthermore, BC survivors who received chemotherapy and ET had an increased risk for sexual dysfunction (hazard ratio 1.16 and 1.46, respectively). These findings underscore the importance of recognition and communication regarding survivorship issues, such as sexual health, which can affect medication adherence, quality of life, and outcomes for patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: a systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.200535
2. Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer. 2022;173:113-12 doi: 10.1016/j.ejca.20206.048
3. I-SPY2 Trial Consortium. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6:1355-1362. doi: 10.1001/jamaoncol.2020.2535
4. Panjari M, Bell RJ, Davis SR. Sexual function after breast cancer. J Sex Med. 2011;8:294-302. doi: 10.1111/j.1743-6109.2010.0203x

Many of the persistent problems that breast cancer survivors experience after treatment are not part of the conversation with oncologists during treatment, said Patricia A. Ganz, MD, during a presentation at the European Society for Medical Oncology Breast Cancer annual congress.

Several studies suggest that many breast cancer patients are not well prepared to move forward after a breast cancer diagnosis and subsequent treatments, continued Dr. Ganz, who works at the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

Meeting the survivorship needs of breast cancer patients requires addressing both their physical and psychosocial needs, Dr. Ganz said. She explained how to achieve that, but first pointed to research elaborating on what's missing from some breast cancer survivors' care and barriers to these patients having their variety of health-related needs met.

In a 2021 study published in the Journal of Cancer Survivorship, Dr. Ganz and colleagues conducted a survey of approximately 200 medical oncologists in the United States. They determined that less than 50% provide survivorship care plans to patients at the end of treatment or communicate with patients’ other physicians about follow-up care.

In a secondary analysis of data from the same survey published in 2022 in Breast Cancer Research and Treatment, Dr. Ganz and colleagues examined medical oncologists’ perceived barriers to addressing both physical and psychosocial long-term effects in breast cancer survivors. For both, lack of time was the greatest perceived barrier, cited by nearly two-thirds of oncologists. Other barriers to addressing physical effects included lack of evidence-based, effective interventions, lack of clinical algorithms to guide care, and ambiguity regarding professional responsibility at the end of treatment. Other top barriers to addressing psychosocial issues included lack of mental health providers, lack of psychosocial resources, and lack of clinician knowledge and skills.

Data from additional studies suggest that, overall, cancer patients with greater physical burdens, such as more complex and lengthy treatment regimens, also have greater psychosocial needs, Dr. Ganz noted. Plus, approximately 15%-20% of cancer survivors have ongoing anxiety and depressive symptoms.

Shift to primary care

As more breast cancer and other cancer patients survive for longer periods, more care will likely occur in general medical settings, Dr. Ganz said. Issues to be addressed will include the potential increased risk of comorbid conditions for these survivors, and whether survivorship interventions earlier in the disease trajectory will impact survivorship. For cancer patients who achieve remission after treatment, the first 5 years after a diagnosis involves treatment and short-term surveillance for late effects. Beyond 5 years, care for cancer survivors mainly involves primary care and management of any comorbid conditions, as well as surveillance for late effects and recurrences, and awareness of new research.

A patient consultation early in the process after diagnosis is the start of a continuum of care, Dr. Ganz said. A patient consultation should address symptoms related to initial treatments, such as neuropathy, pain, fatigue, and insomnia, as well as the psychological symptoms of anxiety and depression. An early consultation also should evaluate adherence to endocrine therapy and management of symptoms, if needed, with the larger goal of preparing patients for recovery and the transition to survivorship, and what to expect for long-term follow-up.
 

Delivering the three P’s

The “Three P’s” of survivor care for breast cancer patients are palliation, prevention, and promotion of health, according to Dr. Ganz .

The first “P,” for palliative, is a key part of survivorship care, said Dr. Ganz. Palliative care is defined as care that focuses on reducing symptom severity and improving quality of life. The biological effects of cancer treatment can be associated with physical effects, such as functional limitations and frailty, and behavioral/cognitive effects such as depression, fatigue, and cognitive deficits, she said. To manage these effects and provide palliative care, consultation is needed with specialists in relevant areas including mental health, pain management, physical medicine/rehabilitation, endocrinology, cardiology, and neurology.

The second “P,” which is for prevention in survivorship care, refers to ongoing follow-up screening to identify any potentially serious late-onset complications such as osteoporosis or cardiac disease so they can be addressed, said Dr. Ganz. Other considerations include chemoprevention if available and genetic counseling for patients with hereditary cancers. Prevention also includes counseling patients about lifestyle modifications to help prevent additional cancer.

The goal of the third “P,” which is for health promotion, is to promote risk reduction for the health problems associated with accelerated aging that may arise in cancer survivors, said Dr. Ganz.

Health promotion strategies include maintaining a healthy weight, increasing physical activity, and avoiding harmful exposures, she said. Healthy lifestyle interventions can also reduce the risk of other chronic diseases such as diabetes and heart disease.

To that end, Dr. Ganz outlined several behavioral interventions that may mitigate the effects of cancer treatment on the accelerated aging process, including stress reduction in the form of meditation or yoga, cognitive behavioral therapy, improving sleep, increasing physical activity, reducing obesity, and decreasing tobacco and alcohol use. These interventions may help reduce inflammation and promote tissue repair and healing.

For cancer survivors, the life span may be longer than the health span, and these patients may benefit from an integrated model of care, with systematic screening and consolidated appointments, rather than a fragmented model in which departments and referrals are siloed, which may result in conflicting advice or redundancy, said Dr. Ganz.

Looking ahead, more research is needed to explore models of care delivery, as requirements for survivor care will vary among patients and care settings, Dr. Ganz said.

However, regardless of setting, treatment plans and shared decision-making can help reduce potential long-term or late-emerging effects, she said. Developing a survivorship care plan can help patients learn how to enhance their recovery.

During a question and answer session, Dr. Ganz was asked about whether hormone therapy could be used for patients with hormone negative breast cancer. “I think vaginal estrogen can be used if someone is on tamoxifen,” she said. However, “we need to be cautious” in case there are remaining estrogen positive cells, in order to avoid potential metastases, and use of hormone therapy in breast cancer survivors is an individualized decision based in part on quality of life.
 

Engaging a patient’s partner early can be helpful

If possible, engage the patient’s partner in survivorship discussions, said Luzia Travado, PhD, head of psycho-oncology at the Champalimaud Foundation, Lisbon, who presented on the topic of sexuality and commented on survivorship during the discussion. For those women with partners, engaging the partner early in treatment often means they are more likely to play a larger role in the post treatment and long term by providing stability and emotional support.

“Make sure partners are engaged and understand that they have a role, and that this role is valued,” she said. Unfortunately, there are a lot of divorced women with breast cancer, as the disease can take a toll on relationships. However, remember “sexuality is not just sex; it is caring, loving, and intimacy.”

“To end on a positive note, it is important to empower patients, and to give them self-management skills so they can make things even better in their survivorship,” said Dr. Ganz. In spite of discussing difficulties and challenges, one of the goals of the session was to offer potential solutions and answers.

Dr. Ganz disclosed serving as editor of the cancer survivorship section on Up-to-Date, and serving as a consultant for Blue Note Therapeutics, GRAIL, InformedDNA, and Roche-Genentech. Dr. Travado had no relevant financial conflicts to disclose.

Many of the persistent problems that breast cancer survivors experience after treatment are not part of the conversation with oncologists during treatment, said Patricia A. Ganz, MD, during a presentation at the European Society for Medical Oncology Breast Cancer annual congress.

Several studies suggest that many breast cancer patients are not well prepared to move forward after a breast cancer diagnosis and subsequent treatments, continued Dr. Ganz, who works at the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

Meeting the survivorship needs of breast cancer patients requires addressing both their physical and psychosocial needs, Dr. Ganz said. She explained how to achieve that, but first pointed to research elaborating on what's missing from some breast cancer survivors' care and barriers to these patients having their variety of health-related needs met.

In a 2021 study published in the Journal of Cancer Survivorship, Dr. Ganz and colleagues conducted a survey of approximately 200 medical oncologists in the United States. They determined that less than 50% provide survivorship care plans to patients at the end of treatment or communicate with patients’ other physicians about follow-up care.

In a secondary analysis of data from the same survey published in 2022 in Breast Cancer Research and Treatment, Dr. Ganz and colleagues examined medical oncologists’ perceived barriers to addressing both physical and psychosocial long-term effects in breast cancer survivors. For both, lack of time was the greatest perceived barrier, cited by nearly two-thirds of oncologists. Other barriers to addressing physical effects included lack of evidence-based, effective interventions, lack of clinical algorithms to guide care, and ambiguity regarding professional responsibility at the end of treatment. Other top barriers to addressing psychosocial issues included lack of mental health providers, lack of psychosocial resources, and lack of clinician knowledge and skills.

Data from additional studies suggest that, overall, cancer patients with greater physical burdens, such as more complex and lengthy treatment regimens, also have greater psychosocial needs, Dr. Ganz noted. Plus, approximately 15%-20% of cancer survivors have ongoing anxiety and depressive symptoms.

Shift to primary care

As more breast cancer and other cancer patients survive for longer periods, more care will likely occur in general medical settings, Dr. Ganz said. Issues to be addressed will include the potential increased risk of comorbid conditions for these survivors, and whether survivorship interventions earlier in the disease trajectory will impact survivorship. For cancer patients who achieve remission after treatment, the first 5 years after a diagnosis involves treatment and short-term surveillance for late effects. Beyond 5 years, care for cancer survivors mainly involves primary care and management of any comorbid conditions, as well as surveillance for late effects and recurrences, and awareness of new research.

A patient consultation early in the process after diagnosis is the start of a continuum of care, Dr. Ganz said. A patient consultation should address symptoms related to initial treatments, such as neuropathy, pain, fatigue, and insomnia, as well as the psychological symptoms of anxiety and depression. An early consultation also should evaluate adherence to endocrine therapy and management of symptoms, if needed, with the larger goal of preparing patients for recovery and the transition to survivorship, and what to expect for long-term follow-up.
 

Delivering the three P’s

The “Three P’s” of survivor care for breast cancer patients are palliation, prevention, and promotion of health, according to Dr. Ganz .

The first “P,” for palliative, is a key part of survivorship care, said Dr. Ganz. Palliative care is defined as care that focuses on reducing symptom severity and improving quality of life. The biological effects of cancer treatment can be associated with physical effects, such as functional limitations and frailty, and behavioral/cognitive effects such as depression, fatigue, and cognitive deficits, she said. To manage these effects and provide palliative care, consultation is needed with specialists in relevant areas including mental health, pain management, physical medicine/rehabilitation, endocrinology, cardiology, and neurology.

The second “P,” which is for prevention in survivorship care, refers to ongoing follow-up screening to identify any potentially serious late-onset complications such as osteoporosis or cardiac disease so they can be addressed, said Dr. Ganz. Other considerations include chemoprevention if available and genetic counseling for patients with hereditary cancers. Prevention also includes counseling patients about lifestyle modifications to help prevent additional cancer.

The goal of the third “P,” which is for health promotion, is to promote risk reduction for the health problems associated with accelerated aging that may arise in cancer survivors, said Dr. Ganz.

Health promotion strategies include maintaining a healthy weight, increasing physical activity, and avoiding harmful exposures, she said. Healthy lifestyle interventions can also reduce the risk of other chronic diseases such as diabetes and heart disease.

To that end, Dr. Ganz outlined several behavioral interventions that may mitigate the effects of cancer treatment on the accelerated aging process, including stress reduction in the form of meditation or yoga, cognitive behavioral therapy, improving sleep, increasing physical activity, reducing obesity, and decreasing tobacco and alcohol use. These interventions may help reduce inflammation and promote tissue repair and healing.

For cancer survivors, the life span may be longer than the health span, and these patients may benefit from an integrated model of care, with systematic screening and consolidated appointments, rather than a fragmented model in which departments and referrals are siloed, which may result in conflicting advice or redundancy, said Dr. Ganz.

Looking ahead, more research is needed to explore models of care delivery, as requirements for survivor care will vary among patients and care settings, Dr. Ganz said.

However, regardless of setting, treatment plans and shared decision-making can help reduce potential long-term or late-emerging effects, she said. Developing a survivorship care plan can help patients learn how to enhance their recovery.

During a question and answer session, Dr. Ganz was asked about whether hormone therapy could be used for patients with hormone negative breast cancer. “I think vaginal estrogen can be used if someone is on tamoxifen,” she said. However, “we need to be cautious” in case there are remaining estrogen positive cells, in order to avoid potential metastases, and use of hormone therapy in breast cancer survivors is an individualized decision based in part on quality of life.
 

Engaging a patient’s partner early can be helpful

If possible, engage the patient’s partner in survivorship discussions, said Luzia Travado, PhD, head of psycho-oncology at the Champalimaud Foundation, Lisbon, who presented on the topic of sexuality and commented on survivorship during the discussion. For those women with partners, engaging the partner early in treatment often means they are more likely to play a larger role in the post treatment and long term by providing stability and emotional support.

“Make sure partners are engaged and understand that they have a role, and that this role is valued,” she said. Unfortunately, there are a lot of divorced women with breast cancer, as the disease can take a toll on relationships. However, remember “sexuality is not just sex; it is caring, loving, and intimacy.”

“To end on a positive note, it is important to empower patients, and to give them self-management skills so they can make things even better in their survivorship,” said Dr. Ganz. In spite of discussing difficulties and challenges, one of the goals of the session was to offer potential solutions and answers.

Dr. Ganz disclosed serving as editor of the cancer survivorship section on Up-to-Date, and serving as a consultant for Blue Note Therapeutics, GRAIL, InformedDNA, and Roche-Genentech. Dr. Travado had no relevant financial conflicts to disclose.

Many of the persistent problems that breast cancer survivors experience after treatment are not part of the conversation with oncologists during treatment, said Patricia A. Ganz, MD, during a presentation at the European Society for Medical Oncology Breast Cancer annual congress.

Several studies suggest that many breast cancer patients are not well prepared to move forward after a breast cancer diagnosis and subsequent treatments, continued Dr. Ganz, who works at the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

Meeting the survivorship needs of breast cancer patients requires addressing both their physical and psychosocial needs, Dr. Ganz said. She explained how to achieve that, but first pointed to research elaborating on what's missing from some breast cancer survivors' care and barriers to these patients having their variety of health-related needs met.

In a 2021 study published in the Journal of Cancer Survivorship, Dr. Ganz and colleagues conducted a survey of approximately 200 medical oncologists in the United States. They determined that less than 50% provide survivorship care plans to patients at the end of treatment or communicate with patients’ other physicians about follow-up care.

In a secondary analysis of data from the same survey published in 2022 in Breast Cancer Research and Treatment, Dr. Ganz and colleagues examined medical oncologists’ perceived barriers to addressing both physical and psychosocial long-term effects in breast cancer survivors. For both, lack of time was the greatest perceived barrier, cited by nearly two-thirds of oncologists. Other barriers to addressing physical effects included lack of evidence-based, effective interventions, lack of clinical algorithms to guide care, and ambiguity regarding professional responsibility at the end of treatment. Other top barriers to addressing psychosocial issues included lack of mental health providers, lack of psychosocial resources, and lack of clinician knowledge and skills.

Data from additional studies suggest that, overall, cancer patients with greater physical burdens, such as more complex and lengthy treatment regimens, also have greater psychosocial needs, Dr. Ganz noted. Plus, approximately 15%-20% of cancer survivors have ongoing anxiety and depressive symptoms.

Shift to primary care

As more breast cancer and other cancer patients survive for longer periods, more care will likely occur in general medical settings, Dr. Ganz said. Issues to be addressed will include the potential increased risk of comorbid conditions for these survivors, and whether survivorship interventions earlier in the disease trajectory will impact survivorship. For cancer patients who achieve remission after treatment, the first 5 years after a diagnosis involves treatment and short-term surveillance for late effects. Beyond 5 years, care for cancer survivors mainly involves primary care and management of any comorbid conditions, as well as surveillance for late effects and recurrences, and awareness of new research.

A patient consultation early in the process after diagnosis is the start of a continuum of care, Dr. Ganz said. A patient consultation should address symptoms related to initial treatments, such as neuropathy, pain, fatigue, and insomnia, as well as the psychological symptoms of anxiety and depression. An early consultation also should evaluate adherence to endocrine therapy and management of symptoms, if needed, with the larger goal of preparing patients for recovery and the transition to survivorship, and what to expect for long-term follow-up.
 

Delivering the three P’s

The “Three P’s” of survivor care for breast cancer patients are palliation, prevention, and promotion of health, according to Dr. Ganz .

The first “P,” for palliative, is a key part of survivorship care, said Dr. Ganz. Palliative care is defined as care that focuses on reducing symptom severity and improving quality of life. The biological effects of cancer treatment can be associated with physical effects, such as functional limitations and frailty, and behavioral/cognitive effects such as depression, fatigue, and cognitive deficits, she said. To manage these effects and provide palliative care, consultation is needed with specialists in relevant areas including mental health, pain management, physical medicine/rehabilitation, endocrinology, cardiology, and neurology.

The second “P,” which is for prevention in survivorship care, refers to ongoing follow-up screening to identify any potentially serious late-onset complications such as osteoporosis or cardiac disease so they can be addressed, said Dr. Ganz. Other considerations include chemoprevention if available and genetic counseling for patients with hereditary cancers. Prevention also includes counseling patients about lifestyle modifications to help prevent additional cancer.

The goal of the third “P,” which is for health promotion, is to promote risk reduction for the health problems associated with accelerated aging that may arise in cancer survivors, said Dr. Ganz.

Health promotion strategies include maintaining a healthy weight, increasing physical activity, and avoiding harmful exposures, she said. Healthy lifestyle interventions can also reduce the risk of other chronic diseases such as diabetes and heart disease.

To that end, Dr. Ganz outlined several behavioral interventions that may mitigate the effects of cancer treatment on the accelerated aging process, including stress reduction in the form of meditation or yoga, cognitive behavioral therapy, improving sleep, increasing physical activity, reducing obesity, and decreasing tobacco and alcohol use. These interventions may help reduce inflammation and promote tissue repair and healing.

For cancer survivors, the life span may be longer than the health span, and these patients may benefit from an integrated model of care, with systematic screening and consolidated appointments, rather than a fragmented model in which departments and referrals are siloed, which may result in conflicting advice or redundancy, said Dr. Ganz.

Looking ahead, more research is needed to explore models of care delivery, as requirements for survivor care will vary among patients and care settings, Dr. Ganz said.

However, regardless of setting, treatment plans and shared decision-making can help reduce potential long-term or late-emerging effects, she said. Developing a survivorship care plan can help patients learn how to enhance their recovery.

During a question and answer session, Dr. Ganz was asked about whether hormone therapy could be used for patients with hormone negative breast cancer. “I think vaginal estrogen can be used if someone is on tamoxifen,” she said. However, “we need to be cautious” in case there are remaining estrogen positive cells, in order to avoid potential metastases, and use of hormone therapy in breast cancer survivors is an individualized decision based in part on quality of life.
 

Engaging a patient’s partner early can be helpful

If possible, engage the patient’s partner in survivorship discussions, said Luzia Travado, PhD, head of psycho-oncology at the Champalimaud Foundation, Lisbon, who presented on the topic of sexuality and commented on survivorship during the discussion. For those women with partners, engaging the partner early in treatment often means they are more likely to play a larger role in the post treatment and long term by providing stability and emotional support.

“Make sure partners are engaged and understand that they have a role, and that this role is valued,” she said. Unfortunately, there are a lot of divorced women with breast cancer, as the disease can take a toll on relationships. However, remember “sexuality is not just sex; it is caring, loving, and intimacy.”

“To end on a positive note, it is important to empower patients, and to give them self-management skills so they can make things even better in their survivorship,” said Dr. Ganz. In spite of discussing difficulties and challenges, one of the goals of the session was to offer potential solutions and answers.

Dr. Ganz disclosed serving as editor of the cancer survivorship section on Up-to-Date, and serving as a consultant for Blue Note Therapeutics, GRAIL, InformedDNA, and Roche-Genentech. Dr. Travado had no relevant financial conflicts to disclose.

While poly (ADP-ribose) polymerase (PARP) inhibitors clearly show benefit in certain kinds of breast cancer, questions persist about ideal drug targets and the value of combining them with other medications, oncologists explained at the European Society for Medical Oncology Breast Cancer annual congress.

For now, the drugs are only approved in high-risk germline BRCA mutation (gBRCAmut) early breast cancer, oncologist Kevin Punie, MD, of Saint Augustine Hospital in Wilrijk, Belgium, said during a session at the meeting. Combining the drugs with chemotherapy “has not yet demonstrated significant benefits, and this is irrespective whether platinum was part of the chemotherapy backbone.”

PARP is a kind of enzyme that repairs damaged DNA in cells, especially cancerous ones. PARP inhibitors block the enzyme, potentially leading more cancer cells to die, the Dana-Farber Cancer Institute states.

In a separate presentation during the same session, oncologist Andrew Tutt, MBChB, PhD, noted that a study he led – a phase 3, double-blinded, randomized 2021 trial – found that patients with BRCA1- or BRCA2-mutated breast cancer who took the PARP inhibitor olarapib (Lynparza) versus placebo had improved outcomes on several measures, including 3-year invasive disease-free survival (85.9% vs. 77.1%, P < .001). However, the study noted that “olaparib had limited effects on global patient-reported quality of life.”

Dr. Tutt, of the Institute of Cancer Research, London, and Kings College London, said 57% of patients who took olarapib suffered nausea versus 24% of those who took placebo, and fatigue and anemia were also more common in the olarapib group. Anemia can be severe and lead to transfusions in some cases.

As Dr. Punie explained, there are many reasons to consider combining PARP inhibitors with other treatments such as chemotherapy, immunotherapy, and radiotherapy. The combinations may have synergetic effects, and they could have potential in both the neoadjuvant and adjuvant settings.

The combination of the PARP inhibitor olaparib and endocrine therapy is now approved by the European Medicines Agency for the adjuvant treatment of certain patients with germline BRCA1/2 mutations who have HER2-negative, high-risk early breast cancer, Dr. Punie noted.

The 2021 study led by Dr. Tutt reported that treatment or safety differences were found in those who received both olaparib and endocrine therapy versus those who only received olarapib.

So far, Dr. Punie said, “we not yet have enough clinical evidence to say that there’s really synergy between PNP inhibitors and other anticancer therapies.” According to the National Institutes of Health, medical synergy “describes the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”

In regard to chemotherapy, it makes sense that PARP inhibitors would be helpful in combination, Dr. Punie said. DNA damage to cancer cells accumulates during chemotherapy, he said, and they’re more depending on PARP for repair.

Study results so far have been mixed. A 2022 study, for example, found that adding the experimental PARP inhibitor veliparib to the chemotherapy regimen carboplatin-paclitaxel didn’t improve outcomes, he said. A similar study examining the addition of olaparib to carboplatin-paclitaxel is ongoing.

As for combining radiotherapy and PARP inhibitors, Dr. Punie said that preclinical findings are promising, and research is underway. There’s also ongoing research into combining PARP inhibitors with immunotherapy.

Off-label use of olaparib with immunotherapy or sequential treatment may be appropriate in the setting of adjuvant gBRCAmut triple-negative breast cancer with residual disease, he said.

During his presentation, Dr. Tutt called for researchers to investigate the use of PARP inhibitors in the de-escalation of treatment in lower-risk gBRCAmut disease.

“Clearly, some patients require chemotherapy, and we know patients respond very well to neoadjuvant chemotherapy if they have a BRCA mutation, but we don’t yet know who we can de-escalate in,” he said.

He also highlighted the need to reduce anemia in patients on PARP inhibitors, “particularly if we’re moving into lower-risk populations or possibly considering prevention trials.

“The study of PARP inhibitor resistance ... is now urgent, so that we can address it,” he said.

Dr. Punie disclosed financial relationships with AstraZeneca, Eli Lilly, Exact Sciences, Focus Patient, Medscape, MSD, Mundi Pharma, Need, Novartis, Pierre Fabre, Pfizer, F. Hoffmann–La Roche, Sanofi, Seagen, and PharmaMar. Dr. Tutt disclosed financial relationships with Artios, Gilead, MD Anderson, Merck KGaA, Pfizer, Vertex, AstraZeneca, EM Partners, Medscape Education, CRUK, Inbiomotion, Myriad Genetics, and Breast Cancer Now.

While poly (ADP-ribose) polymerase (PARP) inhibitors clearly show benefit in certain kinds of breast cancer, questions persist about ideal drug targets and the value of combining them with other medications, oncologists explained at the European Society for Medical Oncology Breast Cancer annual congress.

For now, the drugs are only approved in high-risk germline BRCA mutation (gBRCAmut) early breast cancer, oncologist Kevin Punie, MD, of Saint Augustine Hospital in Wilrijk, Belgium, said during a session at the meeting. Combining the drugs with chemotherapy “has not yet demonstrated significant benefits, and this is irrespective whether platinum was part of the chemotherapy backbone.”

PARP is a kind of enzyme that repairs damaged DNA in cells, especially cancerous ones. PARP inhibitors block the enzyme, potentially leading more cancer cells to die, the Dana-Farber Cancer Institute states.

In a separate presentation during the same session, oncologist Andrew Tutt, MBChB, PhD, noted that a study he led – a phase 3, double-blinded, randomized 2021 trial – found that patients with BRCA1- or BRCA2-mutated breast cancer who took the PARP inhibitor olarapib (Lynparza) versus placebo had improved outcomes on several measures, including 3-year invasive disease-free survival (85.9% vs. 77.1%, P < .001). However, the study noted that “olaparib had limited effects on global patient-reported quality of life.”

Dr. Tutt, of the Institute of Cancer Research, London, and Kings College London, said 57% of patients who took olarapib suffered nausea versus 24% of those who took placebo, and fatigue and anemia were also more common in the olarapib group. Anemia can be severe and lead to transfusions in some cases.

As Dr. Punie explained, there are many reasons to consider combining PARP inhibitors with other treatments such as chemotherapy, immunotherapy, and radiotherapy. The combinations may have synergetic effects, and they could have potential in both the neoadjuvant and adjuvant settings.

The combination of the PARP inhibitor olaparib and endocrine therapy is now approved by the European Medicines Agency for the adjuvant treatment of certain patients with germline BRCA1/2 mutations who have HER2-negative, high-risk early breast cancer, Dr. Punie noted.

The 2021 study led by Dr. Tutt reported that treatment or safety differences were found in those who received both olaparib and endocrine therapy versus those who only received olarapib.

So far, Dr. Punie said, “we not yet have enough clinical evidence to say that there’s really synergy between PNP inhibitors and other anticancer therapies.” According to the National Institutes of Health, medical synergy “describes the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”

In regard to chemotherapy, it makes sense that PARP inhibitors would be helpful in combination, Dr. Punie said. DNA damage to cancer cells accumulates during chemotherapy, he said, and they’re more depending on PARP for repair.

Study results so far have been mixed. A 2022 study, for example, found that adding the experimental PARP inhibitor veliparib to the chemotherapy regimen carboplatin-paclitaxel didn’t improve outcomes, he said. A similar study examining the addition of olaparib to carboplatin-paclitaxel is ongoing.

As for combining radiotherapy and PARP inhibitors, Dr. Punie said that preclinical findings are promising, and research is underway. There’s also ongoing research into combining PARP inhibitors with immunotherapy.

Off-label use of olaparib with immunotherapy or sequential treatment may be appropriate in the setting of adjuvant gBRCAmut triple-negative breast cancer with residual disease, he said.

During his presentation, Dr. Tutt called for researchers to investigate the use of PARP inhibitors in the de-escalation of treatment in lower-risk gBRCAmut disease.

“Clearly, some patients require chemotherapy, and we know patients respond very well to neoadjuvant chemotherapy if they have a BRCA mutation, but we don’t yet know who we can de-escalate in,” he said.

He also highlighted the need to reduce anemia in patients on PARP inhibitors, “particularly if we’re moving into lower-risk populations or possibly considering prevention trials.

“The study of PARP inhibitor resistance ... is now urgent, so that we can address it,” he said.

Dr. Punie disclosed financial relationships with AstraZeneca, Eli Lilly, Exact Sciences, Focus Patient, Medscape, MSD, Mundi Pharma, Need, Novartis, Pierre Fabre, Pfizer, F. Hoffmann–La Roche, Sanofi, Seagen, and PharmaMar. Dr. Tutt disclosed financial relationships with Artios, Gilead, MD Anderson, Merck KGaA, Pfizer, Vertex, AstraZeneca, EM Partners, Medscape Education, CRUK, Inbiomotion, Myriad Genetics, and Breast Cancer Now.

While poly (ADP-ribose) polymerase (PARP) inhibitors clearly show benefit in certain kinds of breast cancer, questions persist about ideal drug targets and the value of combining them with other medications, oncologists explained at the European Society for Medical Oncology Breast Cancer annual congress.

For now, the drugs are only approved in high-risk germline BRCA mutation (gBRCAmut) early breast cancer, oncologist Kevin Punie, MD, of Saint Augustine Hospital in Wilrijk, Belgium, said during a session at the meeting. Combining the drugs with chemotherapy “has not yet demonstrated significant benefits, and this is irrespective whether platinum was part of the chemotherapy backbone.”

PARP is a kind of enzyme that repairs damaged DNA in cells, especially cancerous ones. PARP inhibitors block the enzyme, potentially leading more cancer cells to die, the Dana-Farber Cancer Institute states.

In a separate presentation during the same session, oncologist Andrew Tutt, MBChB, PhD, noted that a study he led – a phase 3, double-blinded, randomized 2021 trial – found that patients with BRCA1- or BRCA2-mutated breast cancer who took the PARP inhibitor olarapib (Lynparza) versus placebo had improved outcomes on several measures, including 3-year invasive disease-free survival (85.9% vs. 77.1%, P < .001). However, the study noted that “olaparib had limited effects on global patient-reported quality of life.”

Dr. Tutt, of the Institute of Cancer Research, London, and Kings College London, said 57% of patients who took olarapib suffered nausea versus 24% of those who took placebo, and fatigue and anemia were also more common in the olarapib group. Anemia can be severe and lead to transfusions in some cases.

As Dr. Punie explained, there are many reasons to consider combining PARP inhibitors with other treatments such as chemotherapy, immunotherapy, and radiotherapy. The combinations may have synergetic effects, and they could have potential in both the neoadjuvant and adjuvant settings.

The combination of the PARP inhibitor olaparib and endocrine therapy is now approved by the European Medicines Agency for the adjuvant treatment of certain patients with germline BRCA1/2 mutations who have HER2-negative, high-risk early breast cancer, Dr. Punie noted.

The 2021 study led by Dr. Tutt reported that treatment or safety differences were found in those who received both olaparib and endocrine therapy versus those who only received olarapib.

So far, Dr. Punie said, “we not yet have enough clinical evidence to say that there’s really synergy between PNP inhibitors and other anticancer therapies.” According to the National Institutes of Health, medical synergy “describes the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”

In regard to chemotherapy, it makes sense that PARP inhibitors would be helpful in combination, Dr. Punie said. DNA damage to cancer cells accumulates during chemotherapy, he said, and they’re more depending on PARP for repair.

Study results so far have been mixed. A 2022 study, for example, found that adding the experimental PARP inhibitor veliparib to the chemotherapy regimen carboplatin-paclitaxel didn’t improve outcomes, he said. A similar study examining the addition of olaparib to carboplatin-paclitaxel is ongoing.

As for combining radiotherapy and PARP inhibitors, Dr. Punie said that preclinical findings are promising, and research is underway. There’s also ongoing research into combining PARP inhibitors with immunotherapy.

Off-label use of olaparib with immunotherapy or sequential treatment may be appropriate in the setting of adjuvant gBRCAmut triple-negative breast cancer with residual disease, he said.

During his presentation, Dr. Tutt called for researchers to investigate the use of PARP inhibitors in the de-escalation of treatment in lower-risk gBRCAmut disease.

“Clearly, some patients require chemotherapy, and we know patients respond very well to neoadjuvant chemotherapy if they have a BRCA mutation, but we don’t yet know who we can de-escalate in,” he said.

He also highlighted the need to reduce anemia in patients on PARP inhibitors, “particularly if we’re moving into lower-risk populations or possibly considering prevention trials.

“The study of PARP inhibitor resistance ... is now urgent, so that we can address it,” he said.

Dr. Punie disclosed financial relationships with AstraZeneca, Eli Lilly, Exact Sciences, Focus Patient, Medscape, MSD, Mundi Pharma, Need, Novartis, Pierre Fabre, Pfizer, F. Hoffmann–La Roche, Sanofi, Seagen, and PharmaMar. Dr. Tutt disclosed financial relationships with Artios, Gilead, MD Anderson, Merck KGaA, Pfizer, Vertex, AstraZeneca, EM Partners, Medscape Education, CRUK, Inbiomotion, Myriad Genetics, and Breast Cancer Now.