BRCA2 MORE IMPORTANT THAN BRCA1 FOR MALES

July 8, 2010 — Men with the BRCA2 gene mutation have a 7.1% chance of developing breast cancer by age 70 and an 8.6% chance by age 80, according to a new British study published online June 28 in the Journal of Medical Genetics.

This is the largest study to date of BRCA2-affected families, say the researchers, and only the fourth to have assessed lifetime risk in affected men. It strongly defines the breast cancer risk associated with the BRCA2 mutation for men, according to the authors.

"Based on the now 4 studies to assess male breast cancer risks using different study designs, it would appear appropriate to quote lifetime risks (to age 70 to 80 years) of breast cancer to men in the Western world of between 6% and 9%," write the authors, led by Gareth Evans, MD, from the Manchester Academic Health Science Centre in England.

The risk of a male developing breast cancer is much greater with the BRCA2 mutation than with the BRCA1 mutation, said Sining Chen, PhD, from the School of Public Health at the University of Medicine and Dentistry of New Jersey in New Brunswick, who was not involved with the study.

Dr. Chen, who was approached by Medscape Medical News for comment, was a coauthor of one of the other studies on the risk of BRCA-related male breast cancer (J Natl Cancer Inst. 2007;99:1811-1814).

"Our paper indicated that male BRCA1 carriers have a 1.8% chance of developing breast cancer by age 80, compared with an 8.3% chance with BRCA2," she said.

With regard to breast cancer risk associated with BRCA2 by age 80, Dr. Chen's findings (8.3%) were "remarkably similar" to those in the British study (8.6%).

"I'm glad to see the estimates are very close," she said of the BRCA2 data. "There is a lot of uncertainty in estimates when the cancer is this rare."

The British study did not evaluate risk associated with BRCA1 mutations.

Men with female relatives who are BRCA carriers should ask them if they are BRCA2 carriers because of the heightened breast cancer risk, said Dr. Chen.

The authors of the British study suggest a similar awareness.

The risk of developing breast cancer is "sufficient to increase awareness of breast cancer among men in BRCA2 families and to stress the importance of early presentation with breast symptoms," they write.

Study Details

The data from the British study come from a database that includes all male first-degree relatives (FDR) of BRCA2-mutation carriers (male or female) older than 20 years. The families are located in and around Manchester and Birmingham, England.

There were 321 families with proven pathogenic BRCA2 mutations.

There were 905 male FDRs of proven BRCA2-mutation carriers. Sixteen of 905 (2%) had breast cancer (age range, 46 to 74 years; median, 61.7 years). Eight additional male breast cancers occurred among second-degree relatives, including 1 with bilateral disease; 2 were confirmed as mutation positive.

Of the 905 male FDRs, 238 died before the family ascertainment date. Of the remaining 667 male FDRs, 3 had breast cancer. In total, there were 4140 years of follow-up from the date of family ascertainment in genetics departments.

Because the male FDRs in the dataset were all at least 20 years old, this would mean that each subject had a potential 60 years of risk, say the authors. "This would amount to a lifetime risk of 4.32%. However, only half of the FDRs would be mutation carriers; as such, the estimated risk in men would be 8.6%," they report.

This study was supported by the Biomedical Research Centre at Central Manchester Foundation Trust and a grant from the Genesis Appeal. The authors have disclosed no relevant financial relationships.

J Med Genet. Published online June 28, 2010. Abstract