The report follows other studies that generally failed to identify a statistically significant association, but the resources of Great Britain’s National Health Service made it possible to achieve greater power than previous efforts.
“It’s a very difficult disease to study because it’s about 100 times rarer than female breast cancer. To do the equivalent study, you either have to make your study 100 times bigger, or think laterally and approach it a different way. (That’s) why we did a case control study where you identify the cases and find controls, rather than wait for men to develop breast cancer,” said Michael Edwin Jones, PhD, the lead author of the study, which was published online in Breast Cancer Research.
The new study found that men who self-reported infertility had a doubled risk of breast cancer, while there was no difference if the fertility was linked to their female partner. Sex hormones are known to play a key role in female breast cancer, and they have a suspected role in male breast cancer as well, though it’s hard to pin down because there is no concentrated source of exposure like hormone therapy or activity from the ovary to cause spiked levels. “It’s more subtle in men, but there’s a reason to think it’s important,” Dr. Jones said.
Although the results hint at a possible role of sex hormones, the research can’t confirm that. Blood draws were taken from participants, but many were conducted after treatment had begun, leading to inconsistent results. Dr. Jones called for more research into biological mechanisms that might explain the increased risk, and suggested that such efforts could lead to a better understanding of breast cancer overall, since the disease in men is not effected by factors like pregnancy and menopause.
Historically, few clinical trials for breast cancer drugs included men, and this has resulted in few approved treatments. However, the impact of breast cancer on men is increasingly being recognized, and most such trials now accept male patients. The Food and Drug Administration has even produced a guidance document for inclusion of men in development of breast cancer drugs, which states that men should be excluded only if there is a clear scientific rationale. When there are too few male participants to draw direct conclusions, it may be possible to extrapolate findings in women to men for FDA approval, provided the mechanism of action suggests that there should be no difference in efficacy.
The Breast Cancer Now study included 1,998 cases and 1,597 controls, who were asked about infertility and whether they had children. Men with male-origin infertility had a higher risk of breast cancer (odds ratio, 2.03; 95% confidence interval [CI], 1.18-3.49), but not men who reported female-origin infertility (OR, 0.86; 95% CI, 0.51-1.45). There was also a heightened risk among men who had not fathered children versus those who had (OR, 1.50; 95% CI, 1.21-1.86).
The association was statistically significant for invasive tumors (OR, 1.96; P = .02), but only a trend was observed for in situ breast cancer (OR, 1.72; P = .39). A possible explanation is that diagnosis of in situ breast cancer is less common than invasive cancer in men, which could have led to the study being underpowered. “Unfortunately, there were too few in-situ breast cancers to allow us to say anything definitive,” said Dr. Jones.
Dr. Jones has no relevant financial disclosures. The study was funded by Breast Cancer Now.