Breast cancer risk among patients with Klinefelter syndrome

To evaluate male breast cancer (MBC) risk among patients with Klinefelter syndrome (KS) and relate this to possible biological explanations.

A literature review was conducted to identify case series and epidemiologic studies that have evaluated MBC risk among patients with KS.

Case reports without expected values have often led to false impressions of risk. Problems include that a diagnosis of cancer can prompt a karyotypic evaluation and that many cases of KS are unrecognized, resulting in incomplete denominators. Few carefully conducted epidemiologic studies have been undertaken given that both KS and MBC are rare events. The largest study found 19.2- and 57.8-fold increases in incidence and mortality, respectively, with particularly high risks among 47,XXY mosaics. These risks were still approximately 70% lower than among females, contradicting case reports that patients with KS have breast cancer rates similar to females. Altered hormone levels (especially the ratio of oestrogens to androgens), administration of exogenous androgens, gynaecomastia and genetic factors have been offered as possible explanations for the high risks.

Additional well-designed epidemiologic studies are needed to clarify which patients with KS are at a high risk of developing MBC and to distinguish between possible predisposing factors, including altered endogenous hormones.