Effect of BRCA Mutations on Ovarian Reserve After Chemotherapy

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Women with BRCA 1/2 mutations have lower ovarian reserve and experience greater ovarian reserve loss after chemotherapy compared with those who are BRCA wild-type.
Women with BRCA 1/2 mutations have lower ovarian reserve and experience greater ovarian reserve loss after chemotherapy compared with those who are BRCA wild-type.

Women with BRCA mutations experience greater chemotherapy-induced ovarian reserve loss compared with women without BRCA aberrations, according to a study presented at the 2018 San Antonio Breast Cancer Symposium, Texas.1

Ovarian reserve loss is a recognized long-term side effect of chemotherapy that can result in partial or total infertility. As such, the American Society of Clinical Oncology (ASCO) has developed and published a guideline for fertility preservation for pediatric and adult males and females undergoing anticancer treatment.2 Importantly, chemotherapy-induced infertility can have profound effects on quality of life, as it adds both anxiety and emotional strain to an already challenging situation of navigating cancer treatment.

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Ovarian Reserve

Ovarian reserve refers to the primordial follicles that are present in a female's ovaries, which are established during the last 2 trimesters of fetal life. This reserve naturally declines due to age, as follicles are continuously depleted for oocyte development and release. Other factors, such as genetics and environmental influences, affect ovarian reserve.

Chemotherapy-induced ovarian loss occurs with chemotherapy, particularly with alkylating agents, and does not appear to occur with targeted therapies or immunotherapy. This occurs as a result of the loss of primordial follicles, which are lost as a result of follicle death or DNA damage to oocytes. It has also been hypothesized that indirect damage to stromal cells or vasculature may also cause a decline in ovarian reserve.

Ovarian Loss in the Setting of a BRCA Mutation

In the current study, the effect of BRCA mutations on ovarian reserve decline was evaluated because BRCA genes code for enzymes critical for DNA repair.1 As discussed above, DNA damage to oocytes or stromal cells may cause a reduction in primordial follicles.2 The researchers therefore hypothesized that women with pathogenic BRCA 1/2 mutations may demonstrate a greater loss in ovarian reserve after treatment with chemotherapy.1

The prospective, longitudinal study included 117 evaluable women with early-stage breast cancer, who were enrolled prior to undergoing chemotherapy, between January 2009 and November 2017. Sera were collected at baseline and 18 months to 24 months after treatment with chemotherapy and evaluated for antimüllerian hormone (AMH). The data were adjusted by age at collection.

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