By: Jennifer Byrne
Research has led to major improvements in breast cancer diagnosis, treatment and survival. However, men with breast cancer represent only 1% of the U.S. breast cancer population and have not been emphasized in this research.
“Nearly all clinical trial participants have been women,” Michael J. Hassett, MD, MPH, medical oncologist at Dana-Farber Cancer Institute and lead author of ASCO’s guideline on management of male breast cancer, said in an interview with Healio. “When so few men have been included in the trials, it’s hard to draw conclusions about how to treat men vs. women. Considering that more than 95% of breast cancers in men are hormone receptor positive, some have suggested that men and women with breast cancer should be treated differently.”
Despite its relative rarity, male breast cancer resulted in approximately 500 deaths in the U.S. in 2019.
Hassett spoke with Healio about the development of the ASCO guideline, published in Journal of Clinical Oncology, how they compare with the current recommendations for women, and how men with breast cancer should be monitored after treatment.
Question: How did ASCO develop this guideline?
Answer: Many of ASCO’s guidelines are evidence-based. With male breast cancer, that’s hard to do because there isn’t as much literature. We formally reviewed the literature for breast cancer in men and, to the extent that it was informative, used the data to guide our recommendations. But, we also included a consensus development process, in which a panel of experts reviewed all available evidence — including studies of women with breast cancer — and used their best judgment to come up with recommendations for men. To come to consensus, we used a modified Delphi process in which a group of experts came up with and voted on a series of draft recommendations. If there was a high level of agreement, the draft would become a formal recommendation.
Q: What are the recommendations in terms of chemotherapy for men with breast cancer?
A: Decisions about when and what chemotherapy to use, as well as which genomic tests can help estimate the benefit of chemotherapy, should be the same for men and women. For example, although HER2-positive breast cancer is less common in men vs. women, HER2 status should still be used to guide chemotherapy treatment planning in men just as it is used in women.
Q: What does the guideline state regarding treatment of male breast cancer with endocrine treatments?
A: Men are very likely to have ER-positive breast cancer, which means they could benefit substantially from endocrine treatments. The recommendation for men is tamoxifen. Men who are unable to tolerate tamoxifen could receive an aromatase inhibitor given together with gosarelin acetate (Zoladex, TerSera) or a similar agent to suppress the production of testosterone and estrogen. There are less data supporting the use of aromatase inhibitors alone for men and some information suggests they may not be as effective for men compared with women.
Q: How does the ASCO guideline differ from those of the National Comprehensive Cancer Network in terms of routine mammography for men who have been treated for breast cancer?
A: The ASCO guideline recommends mammography for the breast that had the cancer, if a man has had a lumpectomy. And, it recommends offering mammography to men with a history of breast cancer and a genetic predisposing mutation, like a BRCA mutation. The guideline panel did not come to consensus on how to follow a man who has had a mastectomy and doesn’t have an inherited risk factor. Also, there wasn’t sufficient consensus among the panel to recommend mammography for the breast that didn’t have cancer. Lastly, some men don’t have much breast tissue, so mammography might not be technically feasible.
Q: What do the recommendations state about genetic testing for this population?
A: Men who have had breast cancer should be offered genetic counseling and, if they agree, testing for germline mutations. There is a link between breast cancer in men and inherited mutations, such as BRCA.
Q: What do you recommend for men with metastatic disease?
A: The guideline recommends endocrine therapy for men with advanced or metastatic, hormone receptor-positive breast cancer. The first-line recommendation for all men with hormone-receptor positive breast cancer is tamoxifen, whereas for women who are postmenopausal an aromatase inhibitor is typically used. Another important consideration is the use of targeted therapies to guide treatment of metastatic disease. For several targets, including HER2, PD-L1, PIK3CA and germline BRCA mutations, specific treatments have shown benefit. The panel recommends use of the same targeted therapies for men when those targets are present, which is why it is important to test men for those targets.
Q: What other important recommendations did the panel make?
A: The panel did not recommend routine breast MRI screening for men with a history of breast cancer. Regarding the management of side effects from endocrine treatments, the panel recommended using the same nonhormonal approaches in men as are already used in women.
Overall, this guideline addresses an important topic. Thousands of men are diagnosed with breast cancer every year, and we want to ensure they get the best quality treatment. Most ASCO guidelines are evidence-based. However, there are some situations, like breast cancer in men, where large randomized trials are not possible and the only way to devise best practices is through consensus-based guidelines from a panel of experts.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.