In men, the incidence of cancer of the breast is about 1 % of the frequency in females. It has been estimated that about 3.8 % of males with breast cancer have Klinefelter syndrome, giving an extrapolated risk of breast cancer in males with the 47XXY karyotype of about 7 %. This is almost equivalent to the population risk of the disease in females to age 70 years. Studies vary in the extent of risk increase estimated: a relative risk of 5–49 in men has been estimated (Hasle et al. 1995; Swerdlow et al. 2005). There is an increased risk of breast cancer in males carrying mutations in BRCA2, but little data are available on the breast cancer risk in individuals with Klinefelter syndrome who carry such mutations.
Extragonadal malignant germ cell Tumours (teratomas, usually mediastinal, diagnosed before the age of 30 years) are significantly more prevalent in Klinefelter syndrome (relative risk 67), and any individual with early sexual development or testicular growth should be screened by measurement of germ cell Tumours markers, including alpha-fetoprotein and human chorionic gonadotropin-B (Nichols 1992; Derenoncourt et al. 1995; Hasle et al. 1995; Ganslandt et al. 2000; Yong et al. 2000). Testicular Tumours may be more common (perhaps secondary to cryptorchidism), and an association with AML and lymphoma has been proposed (Attard-Montalto et al. 1994), but this has not been substantiated (Machatschek et al. 2004) and may be due to the fact that cytogenetic studies are often performed in individuals with hematological malignancies (Hasle et al. 1995; Keung et al. 2002). A large study of the cancer risks in Klinefelter syndrome by the UK Clinical Cytogenetics Group found an increase in risk for breast (RR 5.2–49.2) and lung (RR 1–1.9) cancers and Hodgkin lymphoma (RR0.8-3.9) and a reduction in risk of prostate (RR 0.02–0.7) cancer (Swerdlow et al. 2005).
The overall risk of cancer in Klinefelter syndrome is not substantially increased (RR 0.7–1.1), any increase being seen mainly in the age group 15– 30 years of age, so that no routine cancer surveillance is recommended.