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A look at risk factors for male breast cancer

Published Sep. 4, 2005

Female breast cancer is relatively common. Although male breast cancer is uncommon, it does exist, albeit at a low frequency in the general population.

There are approximately 1,500 new cases and 400 deaths attributable to male breast cancer each year in the United States alone. Although the number of breast cancers in women are increasing each year, those in men have remained steady in the past 40 years. This may be due to wide application of mammography screening, lifestyle changes and other unknown causes.

Cancer of the male breast accounts for less than 1 percent of all breast cancers. According to a review article by Sasco et al., published in 1993, the female-to-male ratio is 100:1 in Caucasians and 70:1 in African-Americans. These figures are similar to those of the National Cancer Institute's Surveillance, Epidemiology and End Results data.

As in women, breast cancer in men is hormonally driven and results from an imbalance in male and female hormones. Precursors to the female hormone are made in the testicles and the adrenal glands. These are converted to the final female hormone in the liver, kidney, skin, fat and bones. In certain conditions, such as cirrhosis of the liver, excess conversion occurs. Exposure of the breast tissues to larger than normal quantities of the female hormone is one cause of male breast cancer.

Certain other conditions, such as testicular disease, benign breast conditions, Jewish ancestry, family history of male and female breast cancer, increasing age, radiation exposure to the chest wall and Klinefelter's syndrome (men with this syndrome carry an extra female chromosome X) all increase the risk of male breast cancer.

Klinefelter's syndrome is present in less than 0.1 percent of the male population, but when present, it confers a 50-fold increased risk for breast cancer. Men with this condition have atrophied testes and produce less than normal quantities of testosterone, which tips the normal male-to-female hormone ratio in favor of the latter.

Eight percent to 10 percent of all breast cancers are thought to be inherited through the bloodline. Of these, 80 percent are attributable to inheritance of mutant BRCA 1 and 2 genes. Multiple family members with breast and/or ovarian cancer, especially at a young age, increase the probability of belonging to a mutant BRCA family, which in turn increases with increasing number of first- and second-degree relatives with these cancers.

Men who have a BRCA 2 mutation have an excess risk of breast cancer on the order of 4 percent to 35 percent. The exact percentage for BRCA 2 penetrance is not fully known at this time.

A variety of benign testicular problems such as undescended testes, congenital inguinal hernia, orchiectomy, orchitis, testicular injury and infertility all confer additional risk by altering the normal male and female hormonal balance.

Gynecomastia is a benign enlargement of the breasts that occurs normally at infancy, at puberty, in old age and as a side effect of several medications. There is no definite causal relationship between gynecomastia and male breast cancer, but the hormonal imbalances that lead to these two conditions are similar. While gynecomastia is fairly common, male breast cancer is very rare. Therefore, the majority of men with this condition do not have breast cancer and are not at increased risk. If, however, they have one or more of the other risk factors that I described in this article, it is prudent for them to consult their physicians.

Treatment principles are similar to those for women except that more men are found to be hormone receptor positive and, therefore, tend to respond to tamoxifen. There is insufficient data regarding other hormonal agents. Patients treated with chemotherapy likewise fare better than historical controls. Because male breast cancer is such a rare disease, there is a dearth of properly conducted clinical trials; therefore, treatment options are largely derived from female breast cancer data.

In summary, male breast cancer is very rare; however, men who possess any of the above-mentioned risk factors would be considered at a higher risk than the general population, and, because of this, it would be appropriate for them to consult their physicians to properly estimate their risk to assess if they might be candidates for prophylactic measures.

_ V. Upender Rao M.D., FACP, practices at the Cancer and Blood Disease Center in Lecanto.