Summary of Recent Research

I blog about recent papers on male breast cancer, and you can see these posts by following “latest research: paper report” on the main menu above. On this page I have organized these different “paper reports” posts into sections to make them more accessible. (Page updated January 30th, 2017).

How do Men with Breast Cancer do?

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 questions 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 that 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. A 2015 study has shown that molecular subtype is key for understanding outcomes for men with breast cancer, just like for women.

A more fundamental concern for all such retrospective studies was raised in 2014: central cancer registries may be misclassifying sex particularly when it comes to breast cancer, and so some retrospective studies may be suspect. Another reason the prospective studies will be essential.

Molecular Studies on Male Breast Cancer – are they different from female breast cancers?

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” where 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.

Most studies emphasize the similarities between breast cancer in women and men. This includes work showing that molecular classification puts most male breast cancers in the same group as ER/PR+ female breast cancer. Furthermore, an in-depth mutational profile suggested that familial male breast cancers have similarities with luminal A female breast cancers with rare TP53 mutations.

Some differences have also been found. Broad-based studies of the genome have recently shown that while at the highest level male and female breast cancers are similar, there are also differences at various levels:

Also, an unusual BRCA2 mutation was recently reported to be associated with male breast cancer in a case, and a new BRCA2-associated protein was also implicated in the disease, suggesting the importance of this pathway.

The evidence that while overall male and female breast cancers share many similarities must be seen increasingly in the light of findings that there are specific differences when one examines the details. With conventional chemotherapy and endocrine therapy these subtle differences may not be all that important – certainly, they are unlikely to influence therapy choice. But when it comes to precision medicine they may well turn out to be key.

Causes of Male Breast Cancer

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 that the precursor lesion for most male breast cancer is ductal carcinoma in situ (DCIS), 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 – 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 that 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 that there’s more to the elevation of the endogenous hormones than just E2.

Another 2015 study showed that taking hormone therapy for benign prostate hyperlasia was not a risk factor for male breast cancer. Interestingly, men who had surgery for their BPH (perhaps because they had a more serious form of the disease) did have an increased risk – androgens and estrogens are closely related in function and in the pathways that make them.

Comparing Male Breast Cancer from Across the World

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 that African American men with male breast cancer do worse in the US than their white counterparts, even if you account for socioeconomics and insurance.

Studies Related to Therapy including Hormone Therapy

Occasionally there are papers not specific to male breast cancer necessarily, that are still interesting , particularly in relation to therapy. One recent example was a paper showing that tamoxifen and melatonin may work together, suggesting that its better to take your tam before going to bed. Of course, more important for how much benefit you get from tamoxifen may be how well you metabolize it. A recent meta-analysis of tamoxifen side effects showed that it is overall well tolerated by men, and the rate of non-compliance is low.

A 2015 report also suggested that aromatase inhibitors work for men, though probably more work needs to be done, including a trial, to see if the outcomes are the same as for tamoxifen.

Research published in 2015 has 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.

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