Risk of Breast and Ovarian Cancers May Differ by BRCA1/2 Mutation Type


Key Points

  • Among BRCA1-mutation carriers, 46% were diagnosed with breast cancer; 12%, with ovarian cancer; 5%, with both; and 37% were diagnosed without cancer.
  • Among BRCA2-mutation carriers, 52% were diagnosed with breast cancer; 6%, with ovarian cancer; 2%, with both; and 40% were diagnosed without cancer.
  • Further analysis indicated that the risk of breast and ovarian cancers varied by the type and location of BRCA1/2 mutations.

Women who have inherited mutations in BRCA1 or BRCA2 (BRCA1/2) have an increased risk of breast and ovarian cancers. However, little has been known about how cancer risks differ by BRCA1/2 mutation type.

In a study involving more than 31,000 women who are carriers of disease-associated mutations in the BRCA1 or BRCA2 gene, researchers identified mutations that were associated with significantly different risks of breast and ovarian cancers. These findings, reported by Rebbeck et al in JAMA, may have implications for risk assessment and cancer prevention decision-making among carriers of these mutations.

Study Details

Timothy R. Rebbeck, PhD, of the Perelman School of Medicine at the University of Pennsylvania, and colleagues evaluated whether BRCA1 or BRCA2 mutation type or location is associated with variation in breast and ovarian cancer risk. The study included 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 33 countries.

Among BRCA1 mutation carriers, 9,052 women (46%) were diagnosed with breast cancer; 2,317 (12%), with ovarian cancer; 1,041 (5%), with breast and ovarian cancers; and 7,171 (37%), without cancer. Among BRCA2 mutation carriers, 6,180 women (52%) were diagnosed with breast cancer; 682 (6%), with ovarian cancer; 272 (2%), with breast and ovarian cancers, and 4,766 (40%), without cancer.

Analysis of the data indicated that the risk of breast and ovarian cancers varied by the type and location of BRCA1/2 mutations. For example, the overall breast cancer risk for BRCA1 mutation carriers under the age of 70 is 59%, and the risk for ovarian cancer is 34%. The new research suggests that women who have a missense mutation, Jewish founder mutation, or a mutation that undergoes NMD with reinitiation have a higher risk of breast cancer (69%). In women who carry a founder mutation, the risk for ovarian cancer decreases to 26%.

“This study is the first step in defining differences in risk associated with location and type of BRCA1 and BRCA2 mutations. Pending additional mechanistic insights into the observed associations and knowledge of mutation-specific risks could provide important information for clinical risk assessment among BRCA1/2 mutation carriers, but further systematic studies will be required to determine the absolute cancer risks associated with different mutations,” the authors wrote.

“It is yet to be determined what level of absolute risk change will influence decision making among carriers of BRCA1/2 mutations. Additional research will be required to better understand what level of risk difference will change decision making and standards of care, such as preventive surgery, for carriers of BRCA1 and BRCA2 mutations,” the study concluded.

Dr. Rebbeck is the corresponding author of the JAMA article.

For full disclosures of the study authors, visit 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.