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Understanding male breast cancer

Breast cancer in men and women differ in levels of cancer-associated gene expression and the relative risk of recurrence after initially successful treatment. Some men have a higher risk than women, whereas others have a much lower risk.

Last summer, I had the privilege of working on an article for Stanford Medicine magazine on the impact of sex and gender on health and health care research. One take-home message is that physicians and researchers ignore differences among individuals at their peril. They affect many aspects of our health.

One interesting example is the recent study by breast oncologist Suleiman Massarweh, MD, who collaborated with researchers from San Francisco Bay Area-based Genomic Health to investigate the molecular differences between breast cancers that occur in men versus those that occur in women. Their research was published online in the Journal of Clinical Oncology.

As Massarweh explained:

Breast cancer in men is understudied and much of what we do know has been extrapolated from our experiences and understanding of breast cancer in women. But breast cancer in men occurs in a completely different physiologic and hormonal environment. It is critical to understand the molecular differences between breast cancers in men and women in order to discern how best to treat it and what to expect in terms of outcomes.

The researchers studied 571,115 women and 3,806 men diagnosed with breast cancer who submitted tumor tissue for genetic testing at Genomic Health between 2004 and 2017. Massarweh and his colleagues compared the expression levels of breast cancer-associated genes among patients' tumors using a commercial assay to assign each cancer a recurrence score between 0 and 100. Higher scores correlate with a greater chance of recurrence.

Massarweh explained their findings:

There are differences in the levels of expression of estrogen-related genes, which surprisingly are expressed more highly in men than women. We also see that men have more distinct risk groups according to [this] testing. There are more men than women with higher-risk disease, but also another group of men with very low-risk disease compared to women.

We think these are different disease subsets in men and we need to better individualize treatments for the different groups.

In particular, the researchers found that, although women with a recurrence score of greater than or equal to 31 experienced a five-year breast-cancer-survival rate of 94.9 percent, the corresponding breast cancer survival in men was only 81 percent.

As Massarweh explained:

In general, breast-cancer-specific mortality is so low at five years that it is overshadowed by mortality from other competing causes. However, patients in the high-risk group have higher mortality from breast cancer, despite deploying chemotherapy more frequently in this group.

Additionally, men have a higher risk of death from breast cancer (as well as from all other causes) compared to women. It is possible that higher breast cancer specific mortality in higher risk disease in men may reflect a pattern of using aromatase inhibitors (drugs that lower estrogen) in men inappropriately instead of tamoxifen, thinking that because they are potentially more effective in women that they might be more effective in men too.

The researchers conclude that further study of breast cancer in men is warranted.

Importantly, however, outcomes are excellent in both men and women with low to intermediate risk estrogen-receptor-positive breast cancer (its tumor cells contain estrogen receptors) and endocrine therapy alone may be adequate even in patients with lymph node involvement.

In contrast, higher risk score patients have a higher mortality despite more frequent use of chemotherapy. This group of patients, which include both men and women, needs further clinical trial testing of new targeted therapies to overcome resistance to anti-estrogen therapies, the researchers feel.

Photo by leo abdelnaby

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