Abstract P1-17-04: Association of BRCA1 mutations with impaired ovarian reserve: A plausible connection between infertility and breast/ovarian cancer risks
Authors: Giordano Sara B , Mittal Navdha , Smith Kristin , Pavone Mary Ellen 
Published: May 2015

Purpose: Mutations in either the BRCA1 or BRCA2 gene are associated with breast and ovarian cancer susceptibility. Lifetime risk estimates for ovarian cancer in the general population indicate that 1.4 percent (14 out of 1,000) of women will be diagnosed with ovarian cancer compared with 15 to 40 percent of women (150-400 out of 1,000) who have a BRCA1 or BRCA2 mutation. For decades, scientists have been attempting to establish a link between the risk of developing cancer and infertility. One prospective study suggested an association with BRCA1 mutations and occult primary ovarian insufficiency. This study showed a novel association between low response to ovarian stimulation and BRCA1 mutations, suggesting a link between double-strand DNA break repair dysfunction, infertility, and breast/ovarian cancer risks.

If substantiated, this may place BRCA mutation positive women at higher risk for chemotherapy induced ovarian failure. We also know that reproductive factors including low parity and infertility may place women at increased risk for breast cancer. Taking into account that 1% of females suffer from primary ovarian insufficiency and that the underlying mechanism remains unknown most of the time, discovery of susceptibility gene may have implications for understanding the link between infertility and breast/ovarian cancer.

We hypothesize that mutations in the BRCA1 gene will adversely affect ovarian reserve, as measured by AMH levels.

Participants and Methods: Subset analysis of serum samples taken from Northwestern Ovarian Cancer Early Detection Program (NOCEDPP) of reproductive aged women who had testing for the BRCA mutation. Using an IRB approved protocol, the NOCEDPP database was searched for women 18-45 years old who had previous BRCA testing. These women must have also provided consent for their stored serum to be used for research purposes. We excluded those with a BRCA2 mutation, a previous history of cancer and/or cancer treatment, and those with a previous unilateral or bilateral oophorectomy or other ovarian surgery. Statistical analysis was done using parametric and nonparametric testing.

Results: A total of 125 met the criteria for our study. 66 women were BRCA1 mutation-positive and 59 were BRCA mutation- negative. The median age for BRCA1 mutation-positive women was 33.5 years while BRCA mutation-negative patients was 37 years (p&lt;0.05). Body mass index, gravidity, parity, and duration of birth control were similar between the groups. Overall median AMH values were 2.6ng/mL in both groups. However, when broken into age groups, BRCA1 mutation-positive women aged 35-39 had a significantly lower AMH level when compared to BRCA mutation-negative women (median 3.6ng/mL vs 1.3ng/mL, p&lt;0.05).

Conclusion: AMH values were significantly lower in BRCA1 mutation-positive women aged 35-39. Women with the BRCA1 mutation should be counseled regarding this potential decrease in ovarian reserve.

Citation Format: Sara B Giordano, Navdha Mittal, Kristin Smith, Mary Ellen Pavone. Association of BRCA1 mutations with impaired ovarian reserve: A plausible connection between infertility and breast/ovarian cancer risks [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-17-04.