Many risk factors have been described for male breast cancer. Although the pathogenesis for the development of this disease is not well established, a common pathway linking many of these risk factors is a hormonal imbalance leading to increased estrogens or decreased testosterone.
Clinical conditions such as Klinefelter's syndrome (XXY) is a risk factor which has been reported in several series. Male breast cancer has been reported to be up to 20 times more common in Klinefelter's patients than in normal males (2). The testosterone levels in these patients is about half of normal males and plasma estrogen levels are also elevated. Chronic liver disease is also well known to result in decreased estrogen metabolism and thus increased plasma levels. Case-control studies have shown a higher incidence of male breast cancer in chronic alcoholics (3). In addition, studies in Egypt where liver fibrosis is commonly caused by bilharziasis (schistosomiasis), a higher incidence of male breast cancer is reported in these patients (3). Gynecomastia is a controversial risk factor with several studies reporting both a positive and negative correlation with male breast cancer (3). It may be that breast cancer and gynecomastia may simply occur more commonly in the same patient since they both probably have a common underlying hormonal cause. Testicular injury such as mumps orchitis and other traumatic injury have also been reported to be associated with increased risk (4).
Exogenous estrogen therapy used in several clinical situations has also been implicated in the development of male breast cancer. Several case reports have described the development of male breast cancer in transsexuals 5-10 years after the initiation of exogenous estrogens as part of their therapeutic regimen (5,6). There are also several case reports of the development of male breast cancer in patients treated with exogenous estrogen therapy for prostate cancer (7).
A positive family history, as in female breast cancer, has been correlated with a higher incidence of disease. Case control studies have shown that the relative risk for first degree relatives (male or female) of male breast cancer patients is increased approximately 2-fold (8,9). There are also several case reports of familial clustering of male breast cancer although no gene defect has been identified (10,11).
Prior exposure to radiation has also been linked to the development of male breast cancer. The median latent period from exposure to tumor development is 30 years, which is very similar to the findings for female breast cancer. The usual source of radiation was either from chest fluoroscopies or upper body radiation for a variety of reasons including thymic enlargement and gynecomastia (3).