Male Breast Cancer: A Scientist’s Perspective

A CANCER scientist, Oliver Bogler, PhD, never expected to become a target of the disease himself. As fate would have it, Dr. Bogler was diagnosed with stage 3 breast cancer at 46 years old, and he embarked on a journey as a cancer patient and clinical trial participant. Today, Dr. Bogler is in remission and taking the drug tamoxifen to try to prevent recurrence. He blogs about the topic at Entering a World of Pink, a male breast cancer blog (malebreastcancerblog.org).

BSTQ: How has becoming a survivor impacted your perspective on the disease?

Dr. Bogler: This experience has given me multiple perspectives as I strive every day to make a difference in the battle against cancer. I am now advocating for more research on male breast cancer, serving as a reviewer on grants for breast cancer from the patient perspective, and I have also served as a volunteer to support men newly facing this diagnosis.

BSTQ: What’s the prognosis for men with breast cancer?

Dr. Bogler: In the absence of any large cohort analyses of men, we rely heavily on data from women to help us understand what the future holds for each of us on this journey. However, some papers do look at this question with retrospective studies, which can be very informative, even if based on relatively small numbers. For example, a 2014 analysis of metastatic male breast cancer supported the use of current guidelines for female breast cancer in the treatment of men and suggested similar outcomes can be achieved. The key to understanding the prognosis for female breast cancer (all cancer, really) is classification into subtypes based on clinically meaningful characteristics. For instance, a 2015 study showed that molecular subtype is key for understanding outcomes for men with breast cancer, just like women.

BSTQ: Are molecular studies on male breast cancer different from female breast cancers?

Dr. Bogler: We are seeing an increase in studies that look at the molecular characteristics of male breast cancer. Having an inventory of the mutations and alterations in any cancer is important in this dawning age of “precision medicine,” in which the goal is to make therapy choices based on such information. This molecular data will also be useful in determining what differences exist between the male and female versions of the disease.

BSTQ: What are the suspected causes of male breast cancer?

Dr. Bogler: Most sporadic cancer is probably caused by a combination of factors coming together: mutations in key genes, environmental factors driving the cancer forward and perhaps a more favorable genetic milieu in some of us. Few papers address the causes, but in some instances, things can be ruled out. A study in 2017 showed the precursor lesion for most male breast cancer is ductal carcinoma in situ, just as it is in women. A 2015 paper looked at whether external hormones could contribute to breast cancer risk, using data from transgender veterans, but no effect was seen in relatively brief exposures to hormones used in gender reassignment therapy.

Interestingly, a study that measured endogenous levels of estrogens in male breast cancer patients showed elevated E2, the most common and potent form, was associated with increased risk. The difference between these studies may be the duration of the elevated hormone experience or may indicate there’s more to the elevation of the endogenous hormones than just E2.

BSTQ: Are there factors that seem influenced by ethnic or racial groups?

Dr. Bogler: In some cancers, there are notable variations across different ethnic/racial groups or environments. Studies are now comparing male breast cancers from different parts of the world. For example, studies in Chinese men have shown that, overall, the picture is the same. However, closer to home, a recent analysis showed African American men with male breast cancer fare worse in the U.S. than their white counterparts, even when accounting for socioeconomics and insurance.

BSTQ: Are there any promising findings related to hormone therapy for men?

Dr. Bogler: Occasionally, there are papers not specific to male breast cancer that are still interesting, particularly in relation to hormone therapy. One recent example was a paper showing tamoxifen and melatonin may work together, suggesting it’s better to take tamoxifen before going to bed. Of course, more important for how much benefit there is from tamoxifen may be how well it is metabolized. A meta-analysis of tamoxifen side effects showed, overall, it is well-tolerated by men, and the rate of noncompliance is low. Additional research raised concern that hormone deprivation therapy, perhaps the most effective treatment for male breast cancer, can lead to mutations in the estrogen receptor, and so circumvention of the hormone therapy.