Germline BRCA1 and BRCA2 mutations in ovarian cancer: utility of a histology-based referral strategy

Obstet Gynecol. 2012 Aug;120(2 Pt 1):235-40. doi: 10.1097/AOG.0b013e31825f3576.


Objective: To estimate the frequency of BRCA1 and BRCA2 germline mutations in women with nonmucinous epithelial ovarian carcinoma unselected for a family history of breast or ovarian cancer.

Methods: From 2004 to 2009, women undergoing surgical staging for nonmucinous epithelial ovarian carcinoma, including fallopian tube and primary peritoneal carcinoma, were invited to participate in tumor banking and genetic counseling for BRCA1 and BRCA2 mutations. Pathology and family history obtained by the gynecologic oncology surgeon and genetic counselors were reviewed.

Results: Of 131 women fulfilling entry criteria, germline BRCA1 and BRCA2 mutations were found in 20% (26/131) and were exclusively associated with high-grade serous histology (26/103 [25%]). Restricting BRCA1 and BRCA2 testing to women with family histories of hereditary breast and ovarian cancer, as ascertained by the surgeon, missed 14 mutation carriers, lowering detection rates to 9% (12/131) or 11.6% (12/103) if only considering the patients with high-grade serous histology. This improved to 16% (21/131) or 20.4% (21/103) when ascertained by the genetic counselor; however, 5 of 26 (19%) mutation carriers did not have a family history of hereditary breast or ovarian cancer.

Conclusion: Germline BRCA1 and BRCA2 mutations in ovarian (pelvic) cancer are associated with high-grade serous histology. The high incidence (25%) of germline BRCA1 and BRCA2 mutations specific to the high-grade serous subtype suggests that genetic assessment of all women diagnosed with high-grade serous ovarian (pelvic) carcinoma will improve detection rates and capture mutation carriers otherwise missed by referral based on family history alone.

Level of evidence: II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cystadenocarcinoma, Serous / genetics*
  • Cystadenocarcinoma, Serous / pathology
  • Female
  • Gene Frequency
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genetic Carrier Screening / methods
  • Germ-Line Mutation
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Referral and Consultation