Breast Cancer Risk In Males

Familial clustering of female breast cancer was demonstrated as early as 1926 (81), and epidemiological studies have shown that although both men and women with breast cancer are more likely to have family histories in first-degree relatives than unaffected individuals, men with breast cancer were even more likely to have a first-degree relative with ovarian cancer than affected women (82,83). It is noteworthy that initial linkage studies of BRCA1 did not reveal an association with male breast cancer (14,84). Linkage studies for BRCA2, on the other hand, did contain male breast cancer cases (16). Germline analyses of 50 men affected with breast cancer unselected for family history revealed that 14% of these men carried a BRCA2 mutation (85). Easton et al. (52), in a study of two large kindreds linked to BRCA2, estimated the cumulative risk of breast cancer in male carriers to be 6.3% by the age of 70 years. In an analysis of 164 BRCA2 kindreds, a similar estimate for cumulative risk emerged: 6.9% for male breast cancer by the age of 80 years, 80 to 100 times the general population risk (34). Thorlacius et al. (63) studied 34 male and 541 female breast cancer cases in Iceland, unselected for family history. Thirteen of these 34 men (38%) had the Icelandic BRCA2 founder mutation compared to a 10.4% carrier rate among the 541 women. This suggests a high index of suspicion for BRCA2 mutations in kindreds with male breast cancer, a fact that has been incorporated into predictive models of BRCA1/2 prevalence (86). A German study of breast and ovarian cancer patients found that 23% harbored mutations in BRCA2 if there was at least one case of male breast cancer in the family (87). Although the risk of breast cancer in male BRCA1 carriers is less than for BRCA2, it is not inconsiderable. The frequency of the BRCA1 mutations among Ashkenazi male breast cancer patients in Israel was three to four times the expected rate (88). Brose et al. (55) estimated a 58-fold increase in risk of breast cancer among 483 males carrying BRCA1 mutations. Finally, although the risk of breast cancer for men with BRCA1/2 mutations is a fraction of that for women, at least one study has estimated the overall lifetime risk of any cancer for male relatives of BRCA2 mutation carriers is higher than that for female relatives (77). If true, BRCA2 testing criteria, currently almost exclusively based on the clinical discovery of breast and ovarian cancer cases, may need to be more inclusive.

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