Men with breast cancer have lower survival rates than women

When doctors and scientists come to his table at national cancer meetings, Michael Singer says he feels a bit like a caged specimen. “They look at me with that bewildered look, ‘oh, so this is what a male breast cancer patient looks like,’ ” quips the retired 59-year-old from the Bronx, N.Y.

With many diseases, women receive procedures and drugs that were largely tested in men. Breast cancer has the opposite problem: Men make up less than 1 percent of breast cancer cases and often receive treatment based on data collected in women.

What’s more, breast cancer in men has been rising. Diagnoses have gone from 0.85 per 100,000 men in the United States in 1975 to 1.21 per 100,000 in 2016. This year, an estimated 2,670 U.S. males will develop the disease. And a new analysis confirms what smaller studies have suggested: Men with breast cancer fare worse than their female counterparts. 

The study, published September 19 in JAMA Oncology, is the largest of its kind. It analyzed registry data on 1,816,733 U.S. patients — including 16,025 men — who were diagnosed with breast cancer from January 2004 to December 2014. At three and five years after diagnosis, as well as at the end of the study period, men had lower survival rates than women. The disparity remained “even after we adjusted for known contributing factors including clinical predictors, socioeconomic status and access to care,” says Xiao-Ou Shu, an epidemiologist at Vanderbilt University Medical Center in Nashville who led the research.

To Laura Esserman, a breast oncologist at the University of California, San Francisco, who wasn’t involved with the study, “the most striking thing is that there was a difference in treatment.” Case in point: Although 84.5 percent of the male breast cancer patients were “hormone-receptor positive” — meaning their tumors grow in response to estrogen or progesterone — only 57.9 percent of those men received standard-of-care endocrine therapy —  drugs that stop hormones from helping breast cancer cells grow. By comparison, only 75.8 percent of female breast cancer patients were hormone-receptor positive, yet 70.2 percent of them got endocrine therapy.

Consistent with past analyses, the new study also found that male breast cancer patients were older when diagnosed, and more likely to have advanced disease, compared with women.

Singer isn’t surprised. Unlike women, who are taught to do breast exams on themselves and advised to have regular mammograms, “guys never touch themselves there,” he says. “We’re never trained to look for early warning signs.” 

When Singer noticed a lump below his left nipple, months passed before he brought it up with his doctor in December 2010. “I was embarrassed,” he says. “I was ignoring it and hoping it would go away.” Weeks later, he learned it was Stage 2 breast cancer and got a mastectomy.

“There are some real barriers for lesions to be found in a timely way,” says Esserman, who heard Singer speak at a breast cancer charity event in September. “His talk really made me more aware of that, and how important it is to make people feel comfortable bringing this to the attention of their physicians and not be embarrassed.”

In addition to shame about having a “woman’s disease,” Esserman says routine screening, which is done only in women and tends to detect earlier-stage disease, could explain some of the gender disparity in treatment outcomes.

Another contributing factor could be compliance with follow-up treatment. After primary treatment, many breast cancer patients get assigned a 5- to 10-year regimen of tamoxifen. This daily pill reduces the risk of cancer recurrence, but also carries side effects such as mood swings, nausea, hot flashes and loss of sex drive. “Right there, you’re going to lose most men,” Singer says.

Even if compliance were not an issue, some experts note that the molecular pathways that produce endocrine effects differ between the sexes, and male breast cancer patients could have alternative pathways to drive tumor growth. That means hormone therapies might not work as well in men, says Xiaoxian Bill Li, a breast pathologist at Emory University in Atlanta whose smaller 2017 study indicated that male breast cancer patients have worse outcomes than females, especially for early-stage disease.

To expand treatment options, the Food and Drug Administration issued a draft guidance in August encouraging drug companies to include men in breast cancer studies. (Last year, the FDA released a guidance document to motivate inclusion of pregnant women (SN: 5/30/18) in clinical trials.) And when clinical trial data is scant, the agency occasionally considers other sources of information. In April, for instance, the FDA expanded the indications for the breast cancer drug palbociclib to include men, based on electronic health records and post-marketing data related to patients’ real-world experiences.

Recently, the agency approved several breast cancer drugs for both men and women even though the clinical trials had no male participants, because the drugs weren’t expected to behave differently between genders, says Richard Pazdur, director of the FDA’s Oncology Center of Excellence.

“This is huge,” Singer says. This is “proof that the tide is turning, that we matter.”