AIM: To evaluate male breast cancer (MBC) risk among patients with Klinefelter 
syndrome (KS) and relate this to possible biological explanations.
METHODS: A literature review was conducted to identify case series and 
epidemiologic studies that have evaluated MBC risk among patients with KS.
RESULTS: 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.
CONCLUSIONS: 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.