Rev Endocr Metab Disord. 2016 Feb 4. [Epub ahead of print]
Many cancers have shown a steady increase in incidence over the time that records have been kept, and one hypothesis has been that environmental factors are responsible. When it comes to cancers that occur in hormone regulated tissues, such as the reproductive systems of men and women, the possibility that molecules that can interfere with the signaling functions of the endocrine hormone system is close at hand, and has been actively investigated.
In this review the role of environmental endocrine disruptors in male disease is explored in depth. The authors consider what the recent literature tells us about the impact of environmental disturbance of a man’s hormone signals on various tissues, including the breast.
(I put findings in inverted commas for this blog entry, because a review article doesn’t report new findings but instead summarizes and synthesizes recent discoveries in a field, a very helpful function.)
After a thorough examination of the impact of endocrine disrupting chemicals on the prostate and testes where there is strong evidence for a role, Sweeney and colleagues turn their attention to the male breast. It will come as no surprise to readers of this blog that they start this section off by setting expectations (emphasis mine):
The female rodent MG [mammary gland] has been the model of choice to study the relation between endocrine disruptors and breast development and cancer. Combined with the rarity of male breast cancers (MBCs), there exists a paucity of knowledge on the effects of EDCs [endocrine disrupting chemicals] on the development of the male breast and its pathologies.
The authors then summarize the circumstantial evidence which suggest that there may be a link between exposure to endocrine disrupting chemicals and male breast cancer, as has been demonstrated in women, while conceding that no direct evidence for this exists yet.
They mention a study that showed that in “a small number of cases, patients with no family history of breast cancer treated with DES [Diethylstilbestrol, an endocrine disruptor] for PC [prostate cancer] later developed bilateral gynecomastia and breast cancer.”
Sweeney and colleagues of course also mention the Camp Lejeune evidence:
A case–control study on the 71 reported cases of MBC [male breast cancer] in residents (1950–1985) of Camp Lejeune, North Carolina, suggested associations between vinyl chloride, tricholoroethylene (TCE) and tetrachloroethylene (PCE) found in the drinking water of Camp Lejeune residents and MBC risk in that population. Exposure to vinyl chloride, TCE, PCE and t-1,2- dichloroethylene (DCE, also found in Camp Lejeune water) was also associated with earlier age onset of MBC.
The association between environmental endocrine disruptors and the condition of gynecomastia, the non-cancerous increase in the size of breast tissue in males, is much stronger. Examples cited here include accidental exposure of workers to aerosolized estrogen in one factory, or a delousing agent in another.
Lastly, in the section on the breast, the authors summarize the very limited data on animal studies, where the development of the male mammary gland was studied in mice and rats exposed to agents that affect the endocrine system. Although not many studies exist, they do provide preliminary evidence that the male breast, like the female breast, responds to such external influences. Increases in the amount of breast tissue and changes in its architecture were observed, but no actual tumors arose in these limited studies.
This review provides a helpful summary of the state of knowledge on endocrine disruptors on the biology of male reproductive systems, and concludes that we do not know enough. All the available evidence points to a possible, maybe even likely, link between endocrine disruption and increased risk of male breast cancer, but it falls short of being definitive. It is hard, at the moment, to even guess what the magnitude of risk increase might be, if it indeed exists. Nevertheless, it follows that release of endocrine disruptors into the environment without such knowledge means we may be taking risks we can’t properly assess. My personal leaning would be to exercise caution.
The preliminary and limited observation that exposure to Diethylstilbestrol was associated with male breast cancer in a small sample of men, and that exposure to other endocrine disruptors causes gynecomastia, makes a pretty good case that men’s breasts respond to these agents by activating cell growth. Interestingly, Diethylstilbestrol also reaches humans via beef as it is found in cattle feed.
While gynecomastia is not generally thought to lead to cancer, it may, by increasing the amount of breast tissue, increase the opportunities for additional events to occur (e.g. gene mutation) that will lead to cancer in rare instances. Furthermore, as the authors discuss, exposure early in life including before birth, may set the tissue up for an increase in cancer risk.
So what do we do about it?
I think providing people with increased information of what they are consuming is essential, and can be done now with warning labels on food. Knowing that the meat you are eating has elevated levels of hormone-active compounds because of the way the animals were raised would at least allow you to make a data-driven decision about what risks you are willing to accept. Of course such labeling opportunities already exist in many countries, including the USA Department of Agriculture.
Then we need more research on male organisms. The animal studies cited in the review are a good start, but more can be done. However, animal studies are unlikely to truly reflect the complexity of human exposure, which would occur over decades and at different developmental stages. Therefore, large registration trials on men are needed to explore the risks – this is of course very difficult as male breast cancer is rare, meaning that many more men would be needed to get a statistically meaningful sample, as compared to women. It seems likely that it will be quite some time before we have a definitive answer on this important question.