Breast Cancer ICYMI

Key clinical point: Addition of atezolizumab to carboplatin+paclitaxel in the neoadjuvant setting improved the pathological complete response (pCR) rate in patients with stage II-III triple-negative breast cancer (TNBC).

Major finding: After a median follow-up of 6.6 months, a significantly higher proportion of patients achieved pCR in the atezolizumab+chemotherapy vs chemotherapy-only group (55.6% vs 18.8%; P  =  .018). However, the increase in the percentage of tumor infiltrating lymphocytes was nominal and not significantly different between both groups (P  =  .36). Grade ≥3 treatment-related adverse events were reported by 62.5% vs 57.8% of patients in the only chemotherapy vs atezolizumab+chemotherapy group, respectively.

Study details: Findings are from the phase 2 NCI-10013 study including 67 patients with previously untreated stage II and III TNBC who were randomly assigned to receive neoadjuvant carboplatin+paclitaxel with or without atezolizumab.

Disclosures: This study was supported by the US National Cancer Institute Cancer Therapy Evaluation Program. Some authors declared receiving research grants or having other financial or non-financial ties with several sources.

Source: Ademuyiwa FO et al. A randomized phase 2 study of neoadjuvant carboplatin and paclitaxel with or without atezolizumab in triple negative breast cancer (TNBC) - NCI 10013. NPJ Breast Cancer. 2022;8(1):134 (Dec 30). Doi: 10.1038/s41523-022-00500-3

Key clinical point: Addition of atezolizumab to carboplatin+paclitaxel in the neoadjuvant setting improved the pathological complete response (pCR) rate in patients with stage II-III triple-negative breast cancer (TNBC).

Major finding: After a median follow-up of 6.6 months, a significantly higher proportion of patients achieved pCR in the atezolizumab+chemotherapy vs chemotherapy-only group (55.6% vs 18.8%; P  =  .018). However, the increase in the percentage of tumor infiltrating lymphocytes was nominal and not significantly different between both groups (P  =  .36). Grade ≥3 treatment-related adverse events were reported by 62.5% vs 57.8% of patients in the only chemotherapy vs atezolizumab+chemotherapy group, respectively.

Study details: Findings are from the phase 2 NCI-10013 study including 67 patients with previously untreated stage II and III TNBC who were randomly assigned to receive neoadjuvant carboplatin+paclitaxel with or without atezolizumab.

Disclosures: This study was supported by the US National Cancer Institute Cancer Therapy Evaluation Program. Some authors declared receiving research grants or having other financial or non-financial ties with several sources.

Source: Ademuyiwa FO et al. A randomized phase 2 study of neoadjuvant carboplatin and paclitaxel with or without atezolizumab in triple negative breast cancer (TNBC) - NCI 10013. NPJ Breast Cancer. 2022;8(1):134 (Dec 30). Doi: 10.1038/s41523-022-00500-3

Key clinical point: Addition of atezolizumab to carboplatin+paclitaxel in the neoadjuvant setting improved the pathological complete response (pCR) rate in patients with stage II-III triple-negative breast cancer (TNBC).

Major finding: After a median follow-up of 6.6 months, a significantly higher proportion of patients achieved pCR in the atezolizumab+chemotherapy vs chemotherapy-only group (55.6% vs 18.8%; P  =  .018). However, the increase in the percentage of tumor infiltrating lymphocytes was nominal and not significantly different between both groups (P  =  .36). Grade ≥3 treatment-related adverse events were reported by 62.5% vs 57.8% of patients in the only chemotherapy vs atezolizumab+chemotherapy group, respectively.

Study details: Findings are from the phase 2 NCI-10013 study including 67 patients with previously untreated stage II and III TNBC who were randomly assigned to receive neoadjuvant carboplatin+paclitaxel with or without atezolizumab.

Disclosures: This study was supported by the US National Cancer Institute Cancer Therapy Evaluation Program. Some authors declared receiving research grants or having other financial or non-financial ties with several sources.

Source: Ademuyiwa FO et al. A randomized phase 2 study of neoadjuvant carboplatin and paclitaxel with or without atezolizumab in triple negative breast cancer (TNBC) - NCI 10013. NPJ Breast Cancer. 2022;8(1):134 (Dec 30). Doi: 10.1038/s41523-022-00500-3

Key clinical point: Exemestane plus ovarian function suppression (OFS) led to a greater reduction in recurrence risk than tamoxifen+OFS in premenopausal women with estrogen or progesterone receptor-positive (ER/PgR+) early breast cancer (BC).

Major finding: There was a significant improvement in 12-year disease-free survival (hazard ratio [HR] 0.79; P < .001) and distant recurrence-free interval (HR 0.83; P  =  .03) with exemestane+OFS vs tamoxifen+OFS, with overall survival outcomes (90.1% vs 89.1%) being excellent in both treatment arms.

Study details: Findings are from a combined analysis of the SOFT and TEXT trials including 4690 premenopausal women with ER/PgR+ early BC who were randomly assigned to receive OFS plus exemestane or tamoxifen.

Disclosures: The SOFT and TEXT are supported by ETOP IBCSG (European Thoracic Oncology Platform, International Breast Cancer Study Group) Partners Foundation, Switzerland. The authors declared serving as consultants or advisors or receiving honoraria, research funding, or travel and accommodation expenses from several sources.

Source: Pagani O, Walley BA, et al for the SOFT and TEXT Investigators and the International Breast Cancer Study Group (a division of ETOP IBCSG Partners Foundation). Adjuvant exemestane with ovarian suppression in premenopausal breast cancer: Long-term follow-up of the combined TEXT and SOFT trials. J Clin Oncol. 2022 (Dec 15). Doi: 10.1200/JCO.22.01064

Key clinical point: Exemestane plus ovarian function suppression (OFS) led to a greater reduction in recurrence risk than tamoxifen+OFS in premenopausal women with estrogen or progesterone receptor-positive (ER/PgR+) early breast cancer (BC).

Major finding: There was a significant improvement in 12-year disease-free survival (hazard ratio [HR] 0.79; P < .001) and distant recurrence-free interval (HR 0.83; P  =  .03) with exemestane+OFS vs tamoxifen+OFS, with overall survival outcomes (90.1% vs 89.1%) being excellent in both treatment arms.

Study details: Findings are from a combined analysis of the SOFT and TEXT trials including 4690 premenopausal women with ER/PgR+ early BC who were randomly assigned to receive OFS plus exemestane or tamoxifen.

Disclosures: The SOFT and TEXT are supported by ETOP IBCSG (European Thoracic Oncology Platform, International Breast Cancer Study Group) Partners Foundation, Switzerland. The authors declared serving as consultants or advisors or receiving honoraria, research funding, or travel and accommodation expenses from several sources.

Source: Pagani O, Walley BA, et al for the SOFT and TEXT Investigators and the International Breast Cancer Study Group (a division of ETOP IBCSG Partners Foundation). Adjuvant exemestane with ovarian suppression in premenopausal breast cancer: Long-term follow-up of the combined TEXT and SOFT trials. J Clin Oncol. 2022 (Dec 15). Doi: 10.1200/JCO.22.01064

Key clinical point: Exemestane plus ovarian function suppression (OFS) led to a greater reduction in recurrence risk than tamoxifen+OFS in premenopausal women with estrogen or progesterone receptor-positive (ER/PgR+) early breast cancer (BC).

Major finding: There was a significant improvement in 12-year disease-free survival (hazard ratio [HR] 0.79; P < .001) and distant recurrence-free interval (HR 0.83; P  =  .03) with exemestane+OFS vs tamoxifen+OFS, with overall survival outcomes (90.1% vs 89.1%) being excellent in both treatment arms.

Study details: Findings are from a combined analysis of the SOFT and TEXT trials including 4690 premenopausal women with ER/PgR+ early BC who were randomly assigned to receive OFS plus exemestane or tamoxifen.

Disclosures: The SOFT and TEXT are supported by ETOP IBCSG (European Thoracic Oncology Platform, International Breast Cancer Study Group) Partners Foundation, Switzerland. The authors declared serving as consultants or advisors or receiving honoraria, research funding, or travel and accommodation expenses from several sources.

Source: Pagani O, Walley BA, et al for the SOFT and TEXT Investigators and the International Breast Cancer Study Group (a division of ETOP IBCSG Partners Foundation). Adjuvant exemestane with ovarian suppression in premenopausal breast cancer: Long-term follow-up of the combined TEXT and SOFT trials. J Clin Oncol. 2022 (Dec 15). Doi: 10.1200/JCO.22.01064

Key clinical point: In patients with germline BRCA1/2-wildtype metastatic triple-negative breast cancer (TNBC) with a BRCA-like phenotype, cisplatin plus veliparib significantly improved progression-free survival (PFS) without causing any unprecedented adverse events.

Major finding: PFS was significantly improved with cisplatin+veliparib vs cisplatin+placebo (hazard ratio 0.57; log-rank P  =  .01) in patients with BRCA-like TNBC, but not in germline BRCA1/2-mutated (P  =  .54) and non-BRCA-like (P  =  .57) groups. No new toxicity signals were observed.

Study details: Findings are from the phase 2 S1416 study including 320 patients with metastatic TNBC (n = 305) or estrogen receptor (ER)-positive/progesterone receptor (PR)-positive/both ER and PR positive, human epidermal growth factor receptor 2-negative BC (n = 15) who were randomly assigned to receive cisplatin with either veliparib or placebo.

Disclosures: This study was funded by the US National Cancer Institute and other sources. Some authors declared receiving grants, payments, or honoraria from; serving on advisory boards for; or having other financial or non-financial ties with several sources.

Source: Rodler E et al. Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2023 (Jan 6). Doi: 10.1016/S1470-2045(22)00739-2

Key clinical point: In patients with germline BRCA1/2-wildtype metastatic triple-negative breast cancer (TNBC) with a BRCA-like phenotype, cisplatin plus veliparib significantly improved progression-free survival (PFS) without causing any unprecedented adverse events.

Major finding: PFS was significantly improved with cisplatin+veliparib vs cisplatin+placebo (hazard ratio 0.57; log-rank P  =  .01) in patients with BRCA-like TNBC, but not in germline BRCA1/2-mutated (P  =  .54) and non-BRCA-like (P  =  .57) groups. No new toxicity signals were observed.

Study details: Findings are from the phase 2 S1416 study including 320 patients with metastatic TNBC (n = 305) or estrogen receptor (ER)-positive/progesterone receptor (PR)-positive/both ER and PR positive, human epidermal growth factor receptor 2-negative BC (n = 15) who were randomly assigned to receive cisplatin with either veliparib or placebo.

Disclosures: This study was funded by the US National Cancer Institute and other sources. Some authors declared receiving grants, payments, or honoraria from; serving on advisory boards for; or having other financial or non-financial ties with several sources.

Source: Rodler E et al. Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2023 (Jan 6). Doi: 10.1016/S1470-2045(22)00739-2

Key clinical point: In patients with germline BRCA1/2-wildtype metastatic triple-negative breast cancer (TNBC) with a BRCA-like phenotype, cisplatin plus veliparib significantly improved progression-free survival (PFS) without causing any unprecedented adverse events.

Major finding: PFS was significantly improved with cisplatin+veliparib vs cisplatin+placebo (hazard ratio 0.57; log-rank P  =  .01) in patients with BRCA-like TNBC, but not in germline BRCA1/2-mutated (P  =  .54) and non-BRCA-like (P  =  .57) groups. No new toxicity signals were observed.

Study details: Findings are from the phase 2 S1416 study including 320 patients with metastatic TNBC (n = 305) or estrogen receptor (ER)-positive/progesterone receptor (PR)-positive/both ER and PR positive, human epidermal growth factor receptor 2-negative BC (n = 15) who were randomly assigned to receive cisplatin with either veliparib or placebo.

Disclosures: This study was funded by the US National Cancer Institute and other sources. Some authors declared receiving grants, payments, or honoraria from; serving on advisory boards for; or having other financial or non-financial ties with several sources.

Source: Rodler E et al. Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2023 (Jan 6). Doi: 10.1016/S1470-2045(22)00739-2

Key clinical point: Women with invasive breast cancer (BC) who have germline pathogenic variants (PV) in BRCA1, BRCA2, CHEK2, or PALB2 have 2-3 times higher risk for contralateral BC than those without these PVs.

Major finding: The overall risk for contralateral BC was significantly elevated in all women with germline PV in BRCA1 (hazard ratio [HR] 2.7; P < .001), BRCA2 (HR 3.0; P < .001), and CHEK2 (HR 1.9; P  =  .03), and in the subset of women with estrogen receptor-negative BC and germline PV in PALB2 (HR 2.9; P  =  .006).

Study details: Findings are from an analysis of the CARRIERS study including 15,104 women with invasive BC who underwent ipsilateral surgery.

Disclosures: This study was supported by US National Institutes of Health grants and other sources. The authors declared serving as consultants or advisors and on speakers’ bureaus; receiving research funding, travel, accommodation expenses, or honoraria; and having other ties with several sources.

Source: Yadav S, Boddicker NJ, et al. Contralateral breast cancer risk among carriers of germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. J Clin Oncol. 2023 (Jan 9). Doi: 10.1200/JCO.22.01239

Key clinical point: Women with invasive breast cancer (BC) who have germline pathogenic variants (PV) in BRCA1, BRCA2, CHEK2, or PALB2 have 2-3 times higher risk for contralateral BC than those without these PVs.

Major finding: The overall risk for contralateral BC was significantly elevated in all women with germline PV in BRCA1 (hazard ratio [HR] 2.7; P < .001), BRCA2 (HR 3.0; P < .001), and CHEK2 (HR 1.9; P  =  .03), and in the subset of women with estrogen receptor-negative BC and germline PV in PALB2 (HR 2.9; P  =  .006).

Study details: Findings are from an analysis of the CARRIERS study including 15,104 women with invasive BC who underwent ipsilateral surgery.

Disclosures: This study was supported by US National Institutes of Health grants and other sources. The authors declared serving as consultants or advisors and on speakers’ bureaus; receiving research funding, travel, accommodation expenses, or honoraria; and having other ties with several sources.

Source: Yadav S, Boddicker NJ, et al. Contralateral breast cancer risk among carriers of germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. J Clin Oncol. 2023 (Jan 9). Doi: 10.1200/JCO.22.01239

Key clinical point: Women with invasive breast cancer (BC) who have germline pathogenic variants (PV) in BRCA1, BRCA2, CHEK2, or PALB2 have 2-3 times higher risk for contralateral BC than those without these PVs.

Major finding: The overall risk for contralateral BC was significantly elevated in all women with germline PV in BRCA1 (hazard ratio [HR] 2.7; P < .001), BRCA2 (HR 3.0; P < .001), and CHEK2 (HR 1.9; P  =  .03), and in the subset of women with estrogen receptor-negative BC and germline PV in PALB2 (HR 2.9; P  =  .006).

Study details: Findings are from an analysis of the CARRIERS study including 15,104 women with invasive BC who underwent ipsilateral surgery.

Disclosures: This study was supported by US National Institutes of Health grants and other sources. The authors declared serving as consultants or advisors and on speakers’ bureaus; receiving research funding, travel, accommodation expenses, or honoraria; and having other ties with several sources.

Source: Yadav S, Boddicker NJ, et al. Contralateral breast cancer risk among carriers of germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. J Clin Oncol. 2023 (Jan 9). Doi: 10.1200/JCO.22.01239

Cancer dietitian Lisa Cianciotta often finds herself sitting across from a patient who suddenly fishes a bottle of antioxidant supplements from their bag and says, “My friend told me this works really well,” or “I read on the Internet that this is supposed to be really good for cancer.” 

Although taking an antioxidant pill sounds harmless, Ms. Cianciotta, a clinical dietitian who works with cancer patients at New York–Presbyterian Hospital, knows well that this popular dietary supplement can interfere with a patient’s radiation or chemotherapy.

But many patients with cancer believe these over-the-counter vitamins, minerals, or herbal remedies will help them, and most use at least one dietary supplement alongside their cancer treatment.

And that leaves Ms. Cianciotta with a delicate conversation ahead of her. 

Drug-supplement interactions are complex, often varying by supplement, cancer, and treatment type, and can do more harm than good. Popular dietary supplements may, for instance, cancel the effects of a cancer treatment, making it less effective, or increase serious side effects, such as liver toxicity. But in other cases, supplementation, such as vitamin D for patients who lack the vitamin, may be beneficial, Ms. Cianciotta said. 

These drug-supplement interactions can be hard to pinpoint, given that more than two-thirds of doctors don’t know their patients are using supplements.

Here’s what patients need to know about the potential risks of supplement use during treatment, and how oncologists can address this thorny, often poorly understood topic with patients.
 

The complex drug-supplement landscape

The list of dietary supplements and how they can interact with different treatments and cancer types is long and nuanced. 

But certain supplements appear to affect cancer treatments regardless of other things and should be avoided. Any supplement that strongly alters the body’s levels of the protein cytochromes P450 is one example. This group of enzymes plays a key role in metabolizing drugs, including chemotherapy and immunotherapy agents. 

Certain supplements – most notably St. John’s wort extract – may decrease or increase the activity of cytochrome P450, which can then  affect the concentrations of anticancer drugs in the blood, said William Figg, PharmD, an associate director of the Center for Cancer Research at the National Cancer Institute in Bethesda, Md. Studies show, for instance, that this common herbal supplement can increase the activity of cytochrome P450, resulting in lower levels of cancer drugs.

Outside of drug metabolism, patients with hormone-related cancers, such as breast and prostate cancers, should steer clear of dietary supplements that can alter levels of testosterone or estrogen, Dr. Figg said. The evergreen shrub ashwagandha, for example, is marketed to reduce stress and fatigue, but can also increase testosterone levels – a potential problem for those with prostate cancer receiving androgen deprivation therapy, which lowers testosterone levels. 

Many oncologists counsel patients against using antioxidant-based dietary supplements – particularly turmeric and green tea extract – while they have radiation therapy and certain chemotherapies. These therapies work by creating an abundance of highly reactive molecules called free radicals in tumor cells, which increase stress within these cells, ultimately killing them off. Antioxidants, in theory, can neutralize this effect, said Skyler Johnson, MD, a radiation oncologist at Huntsman Cancer Institute at the University of Utah, Salt Lake City.  Some studies suggest that antioxidant supplements may lessen the effects of radiation and chemotherapy, although the evidence is mixed.

Some dietary supplements, including high-dose green tea extract and vitamin A, can cause kidney or liver toxicity, and “many cancer patients already have compromised kidney or liver function,” said Jun J. Mao, MD, chief of integrative medicine at Memorial Sloan Kettering Cancer Center in New York. Even herbs that don’t interfere with how well a cancer drug works, such as stevia, can increase treatment-related side effects, such as nausea and vomiting. 

Another potential problem with dietary supplements: It’s nearly impossible to know exactly what’s in them. For instance, just last year, the Food and Drug Administration sent nearly 50 warning letters to companies marketing dietary supplements. The issue is that federal regulations governing production are less strict for supplements than for medications. As a result, some supplements contain ingredients not listed on the label. 

One historical example was the supplement PC-SPES, a mix of eight herbs, marketed to men with prostate cancer. The supplement was recalled in 2002 after certain batches were found to contain traces of prescription drugs, including diethylstilbestrol, ethinyl estradiol, warfarin, and alprazolam.

To further complicate matters, some dietary supplements can be helpful. Most patients with cancer “are malnourished and missing out on nutrients they could be getting from food,” said Ms. Cianciotta.

Patients are tested routinely for vitamin deficiencies and receive supplements as needed, she said. Vitamin D and folic acid are two of the most common deficiencies in this patient population. Vitamin D supplementation can improve outcomes in patients who have received a stem cell transplant by aiding engraftment and rebuilding the immune system, while folic acid supplementation can help to raise low red blood cell counts and hemoglobin levels. 

Although she rarely sees vitamin toxicity, Ms. Cianciotta stressed that more is not always better and supplement use, even when it seems safe or warranted due to a deficiency, should be taken under supervision, and monitored carefully by the patient’s care team. 
 

Bringing supplement use into the light

Too often, providers are unaware of a patient’s supplement use. 

A core reason: Dietary supplements are often touted as natural, which many patients equate with safety, said Samantha Heller, a senior clinical nutritionist at New York (N.Y.) University Langone Health. 

That means patients may not know a supplement can act like a drug and interfere with their cancer treatment, and thus may not see the importance of telling their doctors.

Still, the promise of herbs, vitamins, and minerals can be alluring, and there are many reasons patients decide to partake. One major appeal: Dietary supplements can help some patients feel empowered.

“Cancer is a disease that takes away a lot of control from the individual. Taking supplements or herbs is a way to regain some sense of control,” said Dr. Mao. 

The phenomenon can also be cultural, he said. Some people grow up taking herbs and supplements to stay healthy or combat health woes.

Pressure or advice from family or friends who may think they are helping a loved one with their dietary recommendations may play a role as well. Friends and family “cannot prescribe chemo, but they can buy herbs and supplements,” Dr. Mao said. 

Patients seeking greater control over their health or who feel high levels of anxiety may be more likely to take suggestions from friends and family or more likely to believe false or misleading claims about the efficacy or safety of supplements, explained  medical oncologist William Dahut, MD, chief scientific officer for the American Cancer Society. 

Plus, social media often amplifies and normalizes this misinformation, noted Dr. Johnson. In a 2021 study published in the Journal of the National Cancer Institute, he and colleagues found that one-third of the most popular articles on cancer treatment posted to social media in 2018 and 2019 contained false, inaccurate, or misleading information that was often harmful. 

Some of the false claims centered on unproven, potentially unsafe herbal remedies, according to Dr. Johnson. These included “lung cancer can be cured with cannabis oil” and “golden berries cure and prevent cancer.” 

Given exaggerated claims of “cures,” some patients may keep their supplement use under the radar out of fear they will be judged or criticized. 

“Clinicians should avoid making patients feel judged or telling people not to go online to do their own research,” Dr. Johnson said.

Guiding patients, instead, to accurate sources of online information may be one way to help patients feel empowered, he said. Cancer.gov and the Memorial Sloan Kettering Cancer Center’s About Herbs database provide accessible and accurate information on dietary supplements and cancer treatment for both health care professionals and patients, he noted. 

If a particular supplement is not safe during treatment, providers should be able to explain why, said  Ms. Cianciotta. In a recent study, 80% of health care providers surveyed believed that interactions between herbals and medications could be problematic, but only 15% could explain why. 

“Being able to explain why we are discouraging a particular supplement right now tends to be much better received than just telling a patient not to take something, because it is bad,” she said. 

Another key is listening closely to patients to understand why they may be taking a particular supplement. Does the patient feel out of control? Is nausea a problem? 

“Allowing patients to tell you why they are using a particular supplement will often reveal unmet needs or psychosocial challenges,” Dr. Mao said. This information can allow providers to suggest an evidence-based alternative, such as mindfulness meditation or acupuncture, to manage stress.

And if a patient has received a dietary supplement from well-meaning family and friends?

“Simply telling a patient that a given supplement is useless or harmful could create family tension,” said  Dr. Mao. 

Instead, he recommends reframing the issue. 

“We want to have a better understanding of how patients are tolerating chemo or immunotherapy before throwing other things on top of it. Let them know that now may just not be the right time to add a supplement to the mix,” Dr. Mao said. 

The bottom line: “Patients want to play an active role in their own care, and we want to help them do that in a safe way,” he said. 

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

Cancer dietitian Lisa Cianciotta often finds herself sitting across from a patient who suddenly fishes a bottle of antioxidant supplements from their bag and says, “My friend told me this works really well,” or “I read on the Internet that this is supposed to be really good for cancer.” 

Although taking an antioxidant pill sounds harmless, Ms. Cianciotta, a clinical dietitian who works with cancer patients at New York–Presbyterian Hospital, knows well that this popular dietary supplement can interfere with a patient’s radiation or chemotherapy.

But many patients with cancer believe these over-the-counter vitamins, minerals, or herbal remedies will help them, and most use at least one dietary supplement alongside their cancer treatment.

And that leaves Ms. Cianciotta with a delicate conversation ahead of her. 

Drug-supplement interactions are complex, often varying by supplement, cancer, and treatment type, and can do more harm than good. Popular dietary supplements may, for instance, cancel the effects of a cancer treatment, making it less effective, or increase serious side effects, such as liver toxicity. But in other cases, supplementation, such as vitamin D for patients who lack the vitamin, may be beneficial, Ms. Cianciotta said. 

These drug-supplement interactions can be hard to pinpoint, given that more than two-thirds of doctors don’t know their patients are using supplements.

Here’s what patients need to know about the potential risks of supplement use during treatment, and how oncologists can address this thorny, often poorly understood topic with patients.
 

The complex drug-supplement landscape

The list of dietary supplements and how they can interact with different treatments and cancer types is long and nuanced. 

But certain supplements appear to affect cancer treatments regardless of other things and should be avoided. Any supplement that strongly alters the body’s levels of the protein cytochromes P450 is one example. This group of enzymes plays a key role in metabolizing drugs, including chemotherapy and immunotherapy agents. 

Certain supplements – most notably St. John’s wort extract – may decrease or increase the activity of cytochrome P450, which can then  affect the concentrations of anticancer drugs in the blood, said William Figg, PharmD, an associate director of the Center for Cancer Research at the National Cancer Institute in Bethesda, Md. Studies show, for instance, that this common herbal supplement can increase the activity of cytochrome P450, resulting in lower levels of cancer drugs.

Outside of drug metabolism, patients with hormone-related cancers, such as breast and prostate cancers, should steer clear of dietary supplements that can alter levels of testosterone or estrogen, Dr. Figg said. The evergreen shrub ashwagandha, for example, is marketed to reduce stress and fatigue, but can also increase testosterone levels – a potential problem for those with prostate cancer receiving androgen deprivation therapy, which lowers testosterone levels. 

Many oncologists counsel patients against using antioxidant-based dietary supplements – particularly turmeric and green tea extract – while they have radiation therapy and certain chemotherapies. These therapies work by creating an abundance of highly reactive molecules called free radicals in tumor cells, which increase stress within these cells, ultimately killing them off. Antioxidants, in theory, can neutralize this effect, said Skyler Johnson, MD, a radiation oncologist at Huntsman Cancer Institute at the University of Utah, Salt Lake City.  Some studies suggest that antioxidant supplements may lessen the effects of radiation and chemotherapy, although the evidence is mixed.

Some dietary supplements, including high-dose green tea extract and vitamin A, can cause kidney or liver toxicity, and “many cancer patients already have compromised kidney or liver function,” said Jun J. Mao, MD, chief of integrative medicine at Memorial Sloan Kettering Cancer Center in New York. Even herbs that don’t interfere with how well a cancer drug works, such as stevia, can increase treatment-related side effects, such as nausea and vomiting. 

Another potential problem with dietary supplements: It’s nearly impossible to know exactly what’s in them. For instance, just last year, the Food and Drug Administration sent nearly 50 warning letters to companies marketing dietary supplements. The issue is that federal regulations governing production are less strict for supplements than for medications. As a result, some supplements contain ingredients not listed on the label. 

One historical example was the supplement PC-SPES, a mix of eight herbs, marketed to men with prostate cancer. The supplement was recalled in 2002 after certain batches were found to contain traces of prescription drugs, including diethylstilbestrol, ethinyl estradiol, warfarin, and alprazolam.

To further complicate matters, some dietary supplements can be helpful. Most patients with cancer “are malnourished and missing out on nutrients they could be getting from food,” said Ms. Cianciotta.

Patients are tested routinely for vitamin deficiencies and receive supplements as needed, she said. Vitamin D and folic acid are two of the most common deficiencies in this patient population. Vitamin D supplementation can improve outcomes in patients who have received a stem cell transplant by aiding engraftment and rebuilding the immune system, while folic acid supplementation can help to raise low red blood cell counts and hemoglobin levels. 

Although she rarely sees vitamin toxicity, Ms. Cianciotta stressed that more is not always better and supplement use, even when it seems safe or warranted due to a deficiency, should be taken under supervision, and monitored carefully by the patient’s care team. 
 

Bringing supplement use into the light

Too often, providers are unaware of a patient’s supplement use. 

A core reason: Dietary supplements are often touted as natural, which many patients equate with safety, said Samantha Heller, a senior clinical nutritionist at New York (N.Y.) University Langone Health. 

That means patients may not know a supplement can act like a drug and interfere with their cancer treatment, and thus may not see the importance of telling their doctors.

Still, the promise of herbs, vitamins, and minerals can be alluring, and there are many reasons patients decide to partake. One major appeal: Dietary supplements can help some patients feel empowered.

“Cancer is a disease that takes away a lot of control from the individual. Taking supplements or herbs is a way to regain some sense of control,” said Dr. Mao. 

The phenomenon can also be cultural, he said. Some people grow up taking herbs and supplements to stay healthy or combat health woes.

Pressure or advice from family or friends who may think they are helping a loved one with their dietary recommendations may play a role as well. Friends and family “cannot prescribe chemo, but they can buy herbs and supplements,” Dr. Mao said. 

Patients seeking greater control over their health or who feel high levels of anxiety may be more likely to take suggestions from friends and family or more likely to believe false or misleading claims about the efficacy or safety of supplements, explained  medical oncologist William Dahut, MD, chief scientific officer for the American Cancer Society. 

Plus, social media often amplifies and normalizes this misinformation, noted Dr. Johnson. In a 2021 study published in the Journal of the National Cancer Institute, he and colleagues found that one-third of the most popular articles on cancer treatment posted to social media in 2018 and 2019 contained false, inaccurate, or misleading information that was often harmful. 

Some of the false claims centered on unproven, potentially unsafe herbal remedies, according to Dr. Johnson. These included “lung cancer can be cured with cannabis oil” and “golden berries cure and prevent cancer.” 

Given exaggerated claims of “cures,” some patients may keep their supplement use under the radar out of fear they will be judged or criticized. 

“Clinicians should avoid making patients feel judged or telling people not to go online to do their own research,” Dr. Johnson said.

Guiding patients, instead, to accurate sources of online information may be one way to help patients feel empowered, he said. Cancer.gov and the Memorial Sloan Kettering Cancer Center’s About Herbs database provide accessible and accurate information on dietary supplements and cancer treatment for both health care professionals and patients, he noted. 

If a particular supplement is not safe during treatment, providers should be able to explain why, said  Ms. Cianciotta. In a recent study, 80% of health care providers surveyed believed that interactions between herbals and medications could be problematic, but only 15% could explain why. 

“Being able to explain why we are discouraging a particular supplement right now tends to be much better received than just telling a patient not to take something, because it is bad,” she said. 

Another key is listening closely to patients to understand why they may be taking a particular supplement. Does the patient feel out of control? Is nausea a problem? 

“Allowing patients to tell you why they are using a particular supplement will often reveal unmet needs or psychosocial challenges,” Dr. Mao said. This information can allow providers to suggest an evidence-based alternative, such as mindfulness meditation or acupuncture, to manage stress.

And if a patient has received a dietary supplement from well-meaning family and friends?

“Simply telling a patient that a given supplement is useless or harmful could create family tension,” said  Dr. Mao. 

Instead, he recommends reframing the issue. 

“We want to have a better understanding of how patients are tolerating chemo or immunotherapy before throwing other things on top of it. Let them know that now may just not be the right time to add a supplement to the mix,” Dr. Mao said. 

The bottom line: “Patients want to play an active role in their own care, and we want to help them do that in a safe way,” he said. 

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

Cancer dietitian Lisa Cianciotta often finds herself sitting across from a patient who suddenly fishes a bottle of antioxidant supplements from their bag and says, “My friend told me this works really well,” or “I read on the Internet that this is supposed to be really good for cancer.” 

Although taking an antioxidant pill sounds harmless, Ms. Cianciotta, a clinical dietitian who works with cancer patients at New York–Presbyterian Hospital, knows well that this popular dietary supplement can interfere with a patient’s radiation or chemotherapy.

But many patients with cancer believe these over-the-counter vitamins, minerals, or herbal remedies will help them, and most use at least one dietary supplement alongside their cancer treatment.

And that leaves Ms. Cianciotta with a delicate conversation ahead of her. 

Drug-supplement interactions are complex, often varying by supplement, cancer, and treatment type, and can do more harm than good. Popular dietary supplements may, for instance, cancel the effects of a cancer treatment, making it less effective, or increase serious side effects, such as liver toxicity. But in other cases, supplementation, such as vitamin D for patients who lack the vitamin, may be beneficial, Ms. Cianciotta said. 

These drug-supplement interactions can be hard to pinpoint, given that more than two-thirds of doctors don’t know their patients are using supplements.

Here’s what patients need to know about the potential risks of supplement use during treatment, and how oncologists can address this thorny, often poorly understood topic with patients.
 

The complex drug-supplement landscape

The list of dietary supplements and how they can interact with different treatments and cancer types is long and nuanced. 

But certain supplements appear to affect cancer treatments regardless of other things and should be avoided. Any supplement that strongly alters the body’s levels of the protein cytochromes P450 is one example. This group of enzymes plays a key role in metabolizing drugs, including chemotherapy and immunotherapy agents. 

Certain supplements – most notably St. John’s wort extract – may decrease or increase the activity of cytochrome P450, which can then  affect the concentrations of anticancer drugs in the blood, said William Figg, PharmD, an associate director of the Center for Cancer Research at the National Cancer Institute in Bethesda, Md. Studies show, for instance, that this common herbal supplement can increase the activity of cytochrome P450, resulting in lower levels of cancer drugs.

Outside of drug metabolism, patients with hormone-related cancers, such as breast and prostate cancers, should steer clear of dietary supplements that can alter levels of testosterone or estrogen, Dr. Figg said. The evergreen shrub ashwagandha, for example, is marketed to reduce stress and fatigue, but can also increase testosterone levels – a potential problem for those with prostate cancer receiving androgen deprivation therapy, which lowers testosterone levels. 

Many oncologists counsel patients against using antioxidant-based dietary supplements – particularly turmeric and green tea extract – while they have radiation therapy and certain chemotherapies. These therapies work by creating an abundance of highly reactive molecules called free radicals in tumor cells, which increase stress within these cells, ultimately killing them off. Antioxidants, in theory, can neutralize this effect, said Skyler Johnson, MD, a radiation oncologist at Huntsman Cancer Institute at the University of Utah, Salt Lake City.  Some studies suggest that antioxidant supplements may lessen the effects of radiation and chemotherapy, although the evidence is mixed.

Some dietary supplements, including high-dose green tea extract and vitamin A, can cause kidney or liver toxicity, and “many cancer patients already have compromised kidney or liver function,” said Jun J. Mao, MD, chief of integrative medicine at Memorial Sloan Kettering Cancer Center in New York. Even herbs that don’t interfere with how well a cancer drug works, such as stevia, can increase treatment-related side effects, such as nausea and vomiting. 

Another potential problem with dietary supplements: It’s nearly impossible to know exactly what’s in them. For instance, just last year, the Food and Drug Administration sent nearly 50 warning letters to companies marketing dietary supplements. The issue is that federal regulations governing production are less strict for supplements than for medications. As a result, some supplements contain ingredients not listed on the label. 

One historical example was the supplement PC-SPES, a mix of eight herbs, marketed to men with prostate cancer. The supplement was recalled in 2002 after certain batches were found to contain traces of prescription drugs, including diethylstilbestrol, ethinyl estradiol, warfarin, and alprazolam.

To further complicate matters, some dietary supplements can be helpful. Most patients with cancer “are malnourished and missing out on nutrients they could be getting from food,” said Ms. Cianciotta.

Patients are tested routinely for vitamin deficiencies and receive supplements as needed, she said. Vitamin D and folic acid are two of the most common deficiencies in this patient population. Vitamin D supplementation can improve outcomes in patients who have received a stem cell transplant by aiding engraftment and rebuilding the immune system, while folic acid supplementation can help to raise low red blood cell counts and hemoglobin levels. 

Although she rarely sees vitamin toxicity, Ms. Cianciotta stressed that more is not always better and supplement use, even when it seems safe or warranted due to a deficiency, should be taken under supervision, and monitored carefully by the patient’s care team. 
 

Bringing supplement use into the light

Too often, providers are unaware of a patient’s supplement use. 

A core reason: Dietary supplements are often touted as natural, which many patients equate with safety, said Samantha Heller, a senior clinical nutritionist at New York (N.Y.) University Langone Health. 

That means patients may not know a supplement can act like a drug and interfere with their cancer treatment, and thus may not see the importance of telling their doctors.

Still, the promise of herbs, vitamins, and minerals can be alluring, and there are many reasons patients decide to partake. One major appeal: Dietary supplements can help some patients feel empowered.

“Cancer is a disease that takes away a lot of control from the individual. Taking supplements or herbs is a way to regain some sense of control,” said Dr. Mao. 

The phenomenon can also be cultural, he said. Some people grow up taking herbs and supplements to stay healthy or combat health woes.

Pressure or advice from family or friends who may think they are helping a loved one with their dietary recommendations may play a role as well. Friends and family “cannot prescribe chemo, but they can buy herbs and supplements,” Dr. Mao said. 

Patients seeking greater control over their health or who feel high levels of anxiety may be more likely to take suggestions from friends and family or more likely to believe false or misleading claims about the efficacy or safety of supplements, explained  medical oncologist William Dahut, MD, chief scientific officer for the American Cancer Society. 

Plus, social media often amplifies and normalizes this misinformation, noted Dr. Johnson. In a 2021 study published in the Journal of the National Cancer Institute, he and colleagues found that one-third of the most popular articles on cancer treatment posted to social media in 2018 and 2019 contained false, inaccurate, or misleading information that was often harmful. 

Some of the false claims centered on unproven, potentially unsafe herbal remedies, according to Dr. Johnson. These included “lung cancer can be cured with cannabis oil” and “golden berries cure and prevent cancer.” 

Given exaggerated claims of “cures,” some patients may keep their supplement use under the radar out of fear they will be judged or criticized. 

“Clinicians should avoid making patients feel judged or telling people not to go online to do their own research,” Dr. Johnson said.

Guiding patients, instead, to accurate sources of online information may be one way to help patients feel empowered, he said. Cancer.gov and the Memorial Sloan Kettering Cancer Center’s About Herbs database provide accessible and accurate information on dietary supplements and cancer treatment for both health care professionals and patients, he noted. 

If a particular supplement is not safe during treatment, providers should be able to explain why, said  Ms. Cianciotta. In a recent study, 80% of health care providers surveyed believed that interactions between herbals and medications could be problematic, but only 15% could explain why. 

“Being able to explain why we are discouraging a particular supplement right now tends to be much better received than just telling a patient not to take something, because it is bad,” she said. 

Another key is listening closely to patients to understand why they may be taking a particular supplement. Does the patient feel out of control? Is nausea a problem? 

“Allowing patients to tell you why they are using a particular supplement will often reveal unmet needs or psychosocial challenges,” Dr. Mao said. This information can allow providers to suggest an evidence-based alternative, such as mindfulness meditation or acupuncture, to manage stress.

And if a patient has received a dietary supplement from well-meaning family and friends?

“Simply telling a patient that a given supplement is useless or harmful could create family tension,” said  Dr. Mao. 

Instead, he recommends reframing the issue. 

“We want to have a better understanding of how patients are tolerating chemo or immunotherapy before throwing other things on top of it. Let them know that now may just not be the right time to add a supplement to the mix,” Dr. Mao said. 

The bottom line: “Patients want to play an active role in their own care, and we want to help them do that in a safe way,” he said. 

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

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

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

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

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

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

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

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

Clinical trials underway

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

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

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

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

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

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

Demand may burden health systems

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

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

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

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

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

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

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

Planning and prep in Boston

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

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

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

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

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

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

Out-of-pocket test may widen disparities in care

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

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

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

The first positive test result

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

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

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

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

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

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

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

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

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

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

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

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

Clinical trials underway

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

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

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

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

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

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

Demand may burden health systems

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

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

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

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

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

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

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

Planning and prep in Boston

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

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

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

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

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

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

Out-of-pocket test may widen disparities in care

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

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

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

The first positive test result

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

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

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

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

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

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

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

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

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

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

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

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

Clinical trials underway

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

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

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

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

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

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

Demand may burden health systems

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

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

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

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

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

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

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

Planning and prep in Boston

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

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

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

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

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

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

Out-of-pocket test may widen disparities in care

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

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

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

The first positive test result

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

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

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

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

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

This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.

A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.

Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.

Prior studies¹ have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.

The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.

Additional References

Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival.  J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046

This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.

A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.

Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.

Prior studies¹ have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.

The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.

Additional References

Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival.  J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046

This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.

A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.

Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.

Prior studies¹ have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.

The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.

Additional References

Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival.  J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046

Breast cancer (BC) is the most diagnosed cancer and the second leading cause of cancer deaths in women. In 2022, more than 275,000 women were diagnosed with BC, and at least 43,000 of these cases resulted in death. With targeted drug therapy for treating BC now approved by the US Food and Drug Administration (FDA) and available (or in the late phases of clinical trials and pending availability and FDA approval), clinicians are beginning to be able to move away from a “one-size-fits-all” treatment approach that has been used in the past, enhancing prognosis and survival rates in their patients living with BC. 

The new targeted drug therapies available are more precise and individualized. They treat patients more effectively because they are based on the patient’s own biology. These therapies open the possibility of having more valuable treatment options, which can be beneficial for the outcome of many patients diagnosed with BC—especially the highly aggressive forms that were previously difficult to treat. 

In March 2022, the FDA approved the drug olaparib to treat HER2-, high-risk, early breast cancer (EBC). The approval was made after the conclusion of the phase 3 OlympiA trial. The clinical trial results showed a statistically significant improvement in overall survival rates (by 32%) with adjuvant olaparib compared with placebo for germline BRCA1/2-mutated EBC. 

In August 2022, the FDA approved the antibody drug conjugate fam-trastuzumab deruxtecan-nxki (or T-DXd), which is the first FDA-approved therapy targeted to treat patients who have the HER2-low BC subtype. It is also approved for patients with unresectable or metastatic HER2+ breast cancer who have already been treated with 2 or more prior anti-HER2–based therapies in the metastatic setting. The approval of T-DXd was given on the basis of DESTINY-Breast04, a randomized, multicenter, open-label clinical trial that was published in June 2022. T-DXd had been previously approved in HER2+ metastatic breast cancer.

The results from the phase 3 CAPItello-291 clinical trial of capivasertib in combination with fulvestrant suggests the combination could become a new treatment option for patients with hormone receptor–positive, HER2-low, locally advanced or metastatic BC following recurrence or progression after treatment with endocrine therapy and a CDK4/6 inhibitor. Capivasertib is a novel, selective, ATP-competitive, pan-AKT kinase inhibitor. In clinical trials, the drug was shown to successfully block activity of the cancer-driving protein molecule AKT. This research was presented at the 2022 San Antonio Breast Cancer Symposium, and the findings demonstrated a significant improvement in the overall population, as well as the subgroup of patients with PI3K pathway–altered tumors.

The year 2022 was full of exciting discoveries in the field of targeted drug therapies for treating BC, expanding patients’ treatment options and giving hope to people who have been diagnosed with breast cancer and their loved ones. In addition, emerging technologies such as immunotherapy and new antibody-drug conjugates continue to be evaluated as potential treatment options for treating breast cancer in the near future.

Breast cancer (BC) is the most diagnosed cancer and the second leading cause of cancer deaths in women. In 2022, more than 275,000 women were diagnosed with BC, and at least 43,000 of these cases resulted in death. With targeted drug therapy for treating BC now approved by the US Food and Drug Administration (FDA) and available (or in the late phases of clinical trials and pending availability and FDA approval), clinicians are beginning to be able to move away from a “one-size-fits-all” treatment approach that has been used in the past, enhancing prognosis and survival rates in their patients living with BC. 

The new targeted drug therapies available are more precise and individualized. They treat patients more effectively because they are based on the patient’s own biology. These therapies open the possibility of having more valuable treatment options, which can be beneficial for the outcome of many patients diagnosed with BC—especially the highly aggressive forms that were previously difficult to treat. 

In March 2022, the FDA approved the drug olaparib to treat HER2-, high-risk, early breast cancer (EBC). The approval was made after the conclusion of the phase 3 OlympiA trial. The clinical trial results showed a statistically significant improvement in overall survival rates (by 32%) with adjuvant olaparib compared with placebo for germline BRCA1/2-mutated EBC. 

In August 2022, the FDA approved the antibody drug conjugate fam-trastuzumab deruxtecan-nxki (or T-DXd), which is the first FDA-approved therapy targeted to treat patients who have the HER2-low BC subtype. It is also approved for patients with unresectable or metastatic HER2+ breast cancer who have already been treated with 2 or more prior anti-HER2–based therapies in the metastatic setting. The approval of T-DXd was given on the basis of DESTINY-Breast04, a randomized, multicenter, open-label clinical trial that was published in June 2022. T-DXd had been previously approved in HER2+ metastatic breast cancer.

The results from the phase 3 CAPItello-291 clinical trial of capivasertib in combination with fulvestrant suggests the combination could become a new treatment option for patients with hormone receptor–positive, HER2-low, locally advanced or metastatic BC following recurrence or progression after treatment with endocrine therapy and a CDK4/6 inhibitor. Capivasertib is a novel, selective, ATP-competitive, pan-AKT kinase inhibitor. In clinical trials, the drug was shown to successfully block activity of the cancer-driving protein molecule AKT. This research was presented at the 2022 San Antonio Breast Cancer Symposium, and the findings demonstrated a significant improvement in the overall population, as well as the subgroup of patients with PI3K pathway–altered tumors.

The year 2022 was full of exciting discoveries in the field of targeted drug therapies for treating BC, expanding patients’ treatment options and giving hope to people who have been diagnosed with breast cancer and their loved ones. In addition, emerging technologies such as immunotherapy and new antibody-drug conjugates continue to be evaluated as potential treatment options for treating breast cancer in the near future.

Breast cancer (BC) is the most diagnosed cancer and the second leading cause of cancer deaths in women. In 2022, more than 275,000 women were diagnosed with BC, and at least 43,000 of these cases resulted in death. With targeted drug therapy for treating BC now approved by the US Food and Drug Administration (FDA) and available (or in the late phases of clinical trials and pending availability and FDA approval), clinicians are beginning to be able to move away from a “one-size-fits-all” treatment approach that has been used in the past, enhancing prognosis and survival rates in their patients living with BC. 

The new targeted drug therapies available are more precise and individualized. They treat patients more effectively because they are based on the patient’s own biology. These therapies open the possibility of having more valuable treatment options, which can be beneficial for the outcome of many patients diagnosed with BC—especially the highly aggressive forms that were previously difficult to treat. 

In March 2022, the FDA approved the drug olaparib to treat HER2-, high-risk, early breast cancer (EBC). The approval was made after the conclusion of the phase 3 OlympiA trial. The clinical trial results showed a statistically significant improvement in overall survival rates (by 32%) with adjuvant olaparib compared with placebo for germline BRCA1/2-mutated EBC. 

In August 2022, the FDA approved the antibody drug conjugate fam-trastuzumab deruxtecan-nxki (or T-DXd), which is the first FDA-approved therapy targeted to treat patients who have the HER2-low BC subtype. It is also approved for patients with unresectable or metastatic HER2+ breast cancer who have already been treated with 2 or more prior anti-HER2–based therapies in the metastatic setting. The approval of T-DXd was given on the basis of DESTINY-Breast04, a randomized, multicenter, open-label clinical trial that was published in June 2022. T-DXd had been previously approved in HER2+ metastatic breast cancer.

The results from the phase 3 CAPItello-291 clinical trial of capivasertib in combination with fulvestrant suggests the combination could become a new treatment option for patients with hormone receptor–positive, HER2-low, locally advanced or metastatic BC following recurrence or progression after treatment with endocrine therapy and a CDK4/6 inhibitor. Capivasertib is a novel, selective, ATP-competitive, pan-AKT kinase inhibitor. In clinical trials, the drug was shown to successfully block activity of the cancer-driving protein molecule AKT. This research was presented at the 2022 San Antonio Breast Cancer Symposium, and the findings demonstrated a significant improvement in the overall population, as well as the subgroup of patients with PI3K pathway–altered tumors.

The year 2022 was full of exciting discoveries in the field of targeted drug therapies for treating BC, expanding patients’ treatment options and giving hope to people who have been diagnosed with breast cancer and their loved ones. In addition, emerging technologies such as immunotherapy and new antibody-drug conjugates continue to be evaluated as potential treatment options for treating breast cancer in the near future.

Topical minoxidil is widely used to treat hair loss, but new findings suggest that a combination of oral and topical minoxidil could be effective for women with breast cancer who have experienced alopecia from anticancer treatment.

In a retrospective cohort study of women with breast cancer and anticancer therapy–induced alopecia, researchers found that combining low-dose oral minoxidil (LDOM) and topical minoxidil achieved better results than topical minoxidil alone and that the treatment was well tolerated. A total of 5 of the 37 patients (13.5%) in the combination therapy group achieved a complete response, defined as an improvement of alopecia severity from grade 2 to grade 1, compared with none of the 19 patients in the topical therapy–only group.

In contrast, none of the patients in the combination group experienced worsening of alopecia, compared with two (10.5%) in the topical monotherapy group.

The study was published online in the Journal of the American Academy of Dermatology. Topical minoxidil is approved by the Food and Drug Administration to treat androgenetic alopecia. Oral minoxidil is not approved for treating hair loss but has been receiving increased attention as an adjunctive therapy for hair loss, particularly for women. Oral minoxidil is approved for treating hypertension but at much higher doses.

An increasing number of studies have been conducted on the use of oral minoxidil for the treatment of female pattern hair loss, dating back to a pilot study in 2017, with promising results. The findings suggest that LDOM might be more effective than topical therapy, well tolerated, and more convenient for individuals to take.

Hypothesis generating

In a comment, Kai Johnson, MD, a medical oncologist who specializes in treating patients with breast cancer at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, noted that the study, like most small-scale retrospective studies, is hypothesis generating. However, “I’d be hesitant to broadly recommend this practice of dual therapy – oral and topical minoxidil together – until we see a placebo-controlled prospective study performed demonstrating clinically meaningful benefits for patients.”

Another factor is the study endpoints. “While there was a statistically significant benefit documented with dual therapy in this study, it’s important to have study endpoints that are more patient oriented,” Dr. Johnson said. The most important endpoint for patients would be improvements “in the actual alopecia grade, which did occur in 5 of the 37 of dual-therapy patients, versus 0 topical minoxidil patients.”

George Cotsarelis, MD, chair of the department of dermatology and professor of dermatology at the University of Pennsylvania, Philadelphia, also weighed in. He questioned whether adding the topical therapy to oral minoxidil actually improved the results. “What was missing was a study arm that used the oral alone,” he said in an interview. “So we don’t know how effective the oral therapy would be by itself and if combining it with the topical is really adding anything.”

Oral minoxidil as a treatment for hair loss is gaining traction, and it’s clear that it is effective. However, the risk of side effects is higher, he said. “The risk isn’t that high with the low dose, but it can grow hair on places other than the scalp, and that can be disconcerting.” In this study, two women who took the oral drug reported edema, and one reported headache and dizziness. Hypertrichosis was reported by five patients who received the combination.
 

Study details

In the study, Jeewoo Kang, MD, and colleagues from the Seoul National University evaluated the efficacy of LDOM in 100 patients with breast cancer who had been diagnosed with persistent chemotherapy-induced alopecia (pCIA) and endocrine therapy–induced alopecia (EIA) at a dermatology clinic.

They conducted an analysis of medical records, standardized clinical photographs, and trichoscopic images to evaluate the alopecia pattern, severity, treatment response, and posttreatment changes in vertex hair density and thickness.

Compared with those with EIA alone, patients with pCIA were significantly more likely to have diffuse alopecia (P < .001), and they were more likely to have more severe alopecia, although this difference was not significant (P = .058). Outcomes were evaluated for 56 patients who were treated with minoxidil (19 with topical minoxidil alone and 37 with both LDOM and topical minoxidil) and for whom clinical and trichoscopic photos were available at baseline and at the last follow-up (all patients were scheduled for follow-up at 3-month intervals).

The results showed that those treated with 1.25-5.0 mg/d of oral minoxidil and 5% topical minoxidil solution once a day had better responses (P = .002) and a higher percentage increase in hair density from baseline (P = .003), compared with those who received topical minoxidil monotherapy.

However, changes in hair thickness after treatment were not significantly different between the two groups (P = .540).

In addition to the five (13.5%) cases of hypertrichosis, two cases of edema (5.4%), and one case of headache/dizziness (2.7%) among those who received the combination, there was also one report of palpitations (2.7%). Palpitations were reported in one patient (5%) who received topical monotherapy, the only adverse event reported in this group.

Dr. Johnson noted that, at his institution, a dermatologist is conducting a clinical trial with oncology patients post chemotherapy and endocrine therapy. “She is looking at a similar question, although she is comparing oral minoxidil to topical minoxidil directly rather than in combination.” There is also an active clinical trial at Northwestern University, Chicago, of LDOM alone for patients with chemotherapy-induced alopecia.

“So there is a lot of momentum surrounding this concept, and I feel we will continue to see it come up as a possible treatment option, but more data are needed at this time before it can become standard of care,” Dr. Johnson added.

No funding for the study was reported. The authors disclosed no relevant financial relationships.

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

Topical minoxidil is widely used to treat hair loss, but new findings suggest that a combination of oral and topical minoxidil could be effective for women with breast cancer who have experienced alopecia from anticancer treatment.

In a retrospective cohort study of women with breast cancer and anticancer therapy–induced alopecia, researchers found that combining low-dose oral minoxidil (LDOM) and topical minoxidil achieved better results than topical minoxidil alone and that the treatment was well tolerated. A total of 5 of the 37 patients (13.5%) in the combination therapy group achieved a complete response, defined as an improvement of alopecia severity from grade 2 to grade 1, compared with none of the 19 patients in the topical therapy–only group.

In contrast, none of the patients in the combination group experienced worsening of alopecia, compared with two (10.5%) in the topical monotherapy group.

The study was published online in the Journal of the American Academy of Dermatology. Topical minoxidil is approved by the Food and Drug Administration to treat androgenetic alopecia. Oral minoxidil is not approved for treating hair loss but has been receiving increased attention as an adjunctive therapy for hair loss, particularly for women. Oral minoxidil is approved for treating hypertension but at much higher doses.

An increasing number of studies have been conducted on the use of oral minoxidil for the treatment of female pattern hair loss, dating back to a pilot study in 2017, with promising results. The findings suggest that LDOM might be more effective than topical therapy, well tolerated, and more convenient for individuals to take.

Hypothesis generating

In a comment, Kai Johnson, MD, a medical oncologist who specializes in treating patients with breast cancer at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, noted that the study, like most small-scale retrospective studies, is hypothesis generating. However, “I’d be hesitant to broadly recommend this practice of dual therapy – oral and topical minoxidil together – until we see a placebo-controlled prospective study performed demonstrating clinically meaningful benefits for patients.”

Another factor is the study endpoints. “While there was a statistically significant benefit documented with dual therapy in this study, it’s important to have study endpoints that are more patient oriented,” Dr. Johnson said. The most important endpoint for patients would be improvements “in the actual alopecia grade, which did occur in 5 of the 37 of dual-therapy patients, versus 0 topical minoxidil patients.”

George Cotsarelis, MD, chair of the department of dermatology and professor of dermatology at the University of Pennsylvania, Philadelphia, also weighed in. He questioned whether adding the topical therapy to oral minoxidil actually improved the results. “What was missing was a study arm that used the oral alone,” he said in an interview. “So we don’t know how effective the oral therapy would be by itself and if combining it with the topical is really adding anything.”

Oral minoxidil as a treatment for hair loss is gaining traction, and it’s clear that it is effective. However, the risk of side effects is higher, he said. “The risk isn’t that high with the low dose, but it can grow hair on places other than the scalp, and that can be disconcerting.” In this study, two women who took the oral drug reported edema, and one reported headache and dizziness. Hypertrichosis was reported by five patients who received the combination.
 

Study details

In the study, Jeewoo Kang, MD, and colleagues from the Seoul National University evaluated the efficacy of LDOM in 100 patients with breast cancer who had been diagnosed with persistent chemotherapy-induced alopecia (pCIA) and endocrine therapy–induced alopecia (EIA) at a dermatology clinic.

They conducted an analysis of medical records, standardized clinical photographs, and trichoscopic images to evaluate the alopecia pattern, severity, treatment response, and posttreatment changes in vertex hair density and thickness.

Compared with those with EIA alone, patients with pCIA were significantly more likely to have diffuse alopecia (P < .001), and they were more likely to have more severe alopecia, although this difference was not significant (P = .058). Outcomes were evaluated for 56 patients who were treated with minoxidil (19 with topical minoxidil alone and 37 with both LDOM and topical minoxidil) and for whom clinical and trichoscopic photos were available at baseline and at the last follow-up (all patients were scheduled for follow-up at 3-month intervals).

The results showed that those treated with 1.25-5.0 mg/d of oral minoxidil and 5% topical minoxidil solution once a day had better responses (P = .002) and a higher percentage increase in hair density from baseline (P = .003), compared with those who received topical minoxidil monotherapy.

However, changes in hair thickness after treatment were not significantly different between the two groups (P = .540).

In addition to the five (13.5%) cases of hypertrichosis, two cases of edema (5.4%), and one case of headache/dizziness (2.7%) among those who received the combination, there was also one report of palpitations (2.7%). Palpitations were reported in one patient (5%) who received topical monotherapy, the only adverse event reported in this group.

Dr. Johnson noted that, at his institution, a dermatologist is conducting a clinical trial with oncology patients post chemotherapy and endocrine therapy. “She is looking at a similar question, although she is comparing oral minoxidil to topical minoxidil directly rather than in combination.” There is also an active clinical trial at Northwestern University, Chicago, of LDOM alone for patients with chemotherapy-induced alopecia.

“So there is a lot of momentum surrounding this concept, and I feel we will continue to see it come up as a possible treatment option, but more data are needed at this time before it can become standard of care,” Dr. Johnson added.

No funding for the study was reported. The authors disclosed no relevant financial relationships.

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

Topical minoxidil is widely used to treat hair loss, but new findings suggest that a combination of oral and topical minoxidil could be effective for women with breast cancer who have experienced alopecia from anticancer treatment.

In a retrospective cohort study of women with breast cancer and anticancer therapy–induced alopecia, researchers found that combining low-dose oral minoxidil (LDOM) and topical minoxidil achieved better results than topical minoxidil alone and that the treatment was well tolerated. A total of 5 of the 37 patients (13.5%) in the combination therapy group achieved a complete response, defined as an improvement of alopecia severity from grade 2 to grade 1, compared with none of the 19 patients in the topical therapy–only group.

In contrast, none of the patients in the combination group experienced worsening of alopecia, compared with two (10.5%) in the topical monotherapy group.

The study was published online in the Journal of the American Academy of Dermatology. Topical minoxidil is approved by the Food and Drug Administration to treat androgenetic alopecia. Oral minoxidil is not approved for treating hair loss but has been receiving increased attention as an adjunctive therapy for hair loss, particularly for women. Oral minoxidil is approved for treating hypertension but at much higher doses.

An increasing number of studies have been conducted on the use of oral minoxidil for the treatment of female pattern hair loss, dating back to a pilot study in 2017, with promising results. The findings suggest that LDOM might be more effective than topical therapy, well tolerated, and more convenient for individuals to take.

Hypothesis generating

In a comment, Kai Johnson, MD, a medical oncologist who specializes in treating patients with breast cancer at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, noted that the study, like most small-scale retrospective studies, is hypothesis generating. However, “I’d be hesitant to broadly recommend this practice of dual therapy – oral and topical minoxidil together – until we see a placebo-controlled prospective study performed demonstrating clinically meaningful benefits for patients.”

Another factor is the study endpoints. “While there was a statistically significant benefit documented with dual therapy in this study, it’s important to have study endpoints that are more patient oriented,” Dr. Johnson said. The most important endpoint for patients would be improvements “in the actual alopecia grade, which did occur in 5 of the 37 of dual-therapy patients, versus 0 topical minoxidil patients.”

George Cotsarelis, MD, chair of the department of dermatology and professor of dermatology at the University of Pennsylvania, Philadelphia, also weighed in. He questioned whether adding the topical therapy to oral minoxidil actually improved the results. “What was missing was a study arm that used the oral alone,” he said in an interview. “So we don’t know how effective the oral therapy would be by itself and if combining it with the topical is really adding anything.”

Oral minoxidil as a treatment for hair loss is gaining traction, and it’s clear that it is effective. However, the risk of side effects is higher, he said. “The risk isn’t that high with the low dose, but it can grow hair on places other than the scalp, and that can be disconcerting.” In this study, two women who took the oral drug reported edema, and one reported headache and dizziness. Hypertrichosis was reported by five patients who received the combination.
 

Study details

In the study, Jeewoo Kang, MD, and colleagues from the Seoul National University evaluated the efficacy of LDOM in 100 patients with breast cancer who had been diagnosed with persistent chemotherapy-induced alopecia (pCIA) and endocrine therapy–induced alopecia (EIA) at a dermatology clinic.

They conducted an analysis of medical records, standardized clinical photographs, and trichoscopic images to evaluate the alopecia pattern, severity, treatment response, and posttreatment changes in vertex hair density and thickness.

Compared with those with EIA alone, patients with pCIA were significantly more likely to have diffuse alopecia (P < .001), and they were more likely to have more severe alopecia, although this difference was not significant (P = .058). Outcomes were evaluated for 56 patients who were treated with minoxidil (19 with topical minoxidil alone and 37 with both LDOM and topical minoxidil) and for whom clinical and trichoscopic photos were available at baseline and at the last follow-up (all patients were scheduled for follow-up at 3-month intervals).

The results showed that those treated with 1.25-5.0 mg/d of oral minoxidil and 5% topical minoxidil solution once a day had better responses (P = .002) and a higher percentage increase in hair density from baseline (P = .003), compared with those who received topical minoxidil monotherapy.

However, changes in hair thickness after treatment were not significantly different between the two groups (P = .540).

In addition to the five (13.5%) cases of hypertrichosis, two cases of edema (5.4%), and one case of headache/dizziness (2.7%) among those who received the combination, there was also one report of palpitations (2.7%). Palpitations were reported in one patient (5%) who received topical monotherapy, the only adverse event reported in this group.

Dr. Johnson noted that, at his institution, a dermatologist is conducting a clinical trial with oncology patients post chemotherapy and endocrine therapy. “She is looking at a similar question, although she is comparing oral minoxidil to topical minoxidil directly rather than in combination.” There is also an active clinical trial at Northwestern University, Chicago, of LDOM alone for patients with chemotherapy-induced alopecia.

“So there is a lot of momentum surrounding this concept, and I feel we will continue to see it come up as a possible treatment option, but more data are needed at this time before it can become standard of care,” Dr. Johnson added.

No funding for the study was reported. The authors disclosed no relevant financial relationships.

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

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

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

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

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

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

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

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

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

Access to therapies for all patients

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

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

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

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

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

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

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

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

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

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

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

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

Access to therapies for all patients

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

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

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

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

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

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

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

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

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

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

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

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

Access to therapies for all patients

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

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

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

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