Association of BRCA1 mutations with occult primary ovarian insufficiency: A possible explanation for the link between infertility and breast/ovarian cancer risks

Kutluk Oktay, Ja Yeon Kim, David Barad, Samir N. Babayev

Research output: Contribution to journalArticle

204 Scopus citations


Purpose: Germline mutations in BRCA genes are associated with breast and ovarian cancer susceptibility. Because infertility is associated with breast and ovarian cancer risks, we hypothesized that the mutations in the BRCA gene may be associated with low response to fertility treatments. Methods: We performed ovarian stimulation in 126 women with breast cancer by using letrozole and gonadotropins for the purpose of fertility preservation by embryo or oocyte cryopreservation. As surrogates of ovarian reserve, the oocyte yield and the incidence of low response were compared with ovarian stimulation according to BRCA mutation status. Results: Of the 82 women who met the inclusion criteria, 47 women (57%) had undergone BRCA testing, and 14 had a mutation in BRCA genes, of which two were of clinically undetermined significance. In BRCA mutation-positive patients, low ovarian response rate was significantly higher compared with BRCA mutation-negative patients (33.3 v 3.3%; P = .014) and with BRCA-untested women (2.9%; P = .012). All BRCA mutation-positive low responders had BRCA1 mutations, but low response was not encountered in women who were only BRCA2 mutation positive. Compared with controls, BRCA1 mutation- but not BRCA2 mutation-positive women produced lower numbers of eggs (7.4 [95% CI, 3.1 to 17.7] v 12.4 [95% CI, 10.8 to 14.2]; P = .025) and had as many as 38.3 times the odds ratio of low response (95% CI, 4.1 to 353.4; P = .001). Conclusion: BRCA1 mutations are associated with occult primary ovarian insufficiency. This finding may, at least in part, explain the link between infertility and breast/ovarian cancer risks.

Original languageEnglish (US)
Pages (from-to)240-244
Number of pages5
JournalJournal of Clinical Oncology
Issue number2
Publication statusPublished - Jan 10 2010


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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