Abstract P5-09-06: Ovarian reserve and response to controlled ovarian hyperstimulation (COH) in breast cancer women with and without BRCA mutation
Authors: Mailliez A , Keller L , Menu-Hespel S , Plouvier P , D'Orazio E , Basson L , Pigny P , Bonneterre J , Decanter C 
Published: March 2017

Background: 6300 new cases of breast cancer arise in young women under 40 each year in France. Some of them are BRCA 1 or 2 mutation carriers. Most of them receive a potentially gonadotoxic chemotherapy while they have not yet completed their family. Since 2011, a systematic proposal of ovarian reserve follow-up and fertility preservation by oocyte freezing is provided to each young early breast cancer (BC) patients (pts) of our program (NCT 01614704). Preliminary results were presented at the SABCS in 2013. We now investigate the impact of BRCA mutation on the ovarian reserve and the ovarian response to simulation.

Methods: 115 young BC pts were systematically referred to a reproductive medicine centre before starting chemotherapy. Inclusion criteria were age 18 to 38, histologically confirmed invasive breast carcinoma, absence of metastases. According to their personal and familial history, genetic counselling was performed and if the patient met the criteria and agreed, BRCA genes were analysed. Pts in an adjuvant setting and who were asking for fertility preservation underwent COH during the interval between complete surgery and start of adjuvant chemotherapy. Ovarian stimulation protocol consisted in a conventional antagonist protocol with recombinant FSH starting on day 2 of the menstrual cycles. The GnRh antagonist was started on day of the COH and the final oocyte maturation was achieved by an injection of triptorelin 0.2 mg when at least 3 follicles reached 18 mm of diameter. All pts gave their informed consent for COH, egg/embryo freezing and follow-up.

Results: 115 pts achieved pre-treatment AMH and AFC assessment. 60 (52,1%) were eligible for COH in order to cryopreserve egg or embryos. BRCA analysis was performed in 83 pts. 23 did not meet the criteria or refused. 9 analyses are still in process. 17 (20.4%) pts were positive for BRCA mutation (BRCA1: 13; BRCA2: 4) and 66 were not. In the mutation carriers group (n=17), median age was 32 years (Range 25-37). Median initial AMH levels and AFC were 23 pmol/l (5.1–223) and 20 (6-100), respectively. Eight pts underwent COH. Median duration of stimulation was 9,5 days (8-13) with a median cumulative dose of gonadotropins of 2875 UI (1200-5450). The median number of vitrified oocytes was 5,5 (0-15). Two patients chose frozen embryo preservation (1 and 2 eggs respectively). In the non-carriers group (n=66), median age was 31 years (24-37). Median initial AMH levels and AFC were 23.4 pmol/l (0.8-136) and 24 (1-68). 27 pts underwent COH. Median duration of stimulation was 10 days (7-14). Dose of gonadotropins was 2700 UI (1365-5600). The median number of vitrified oocytes was 6 (0-18). The 3 patients chose eggs preservation (0.0 and 3 eggs respectively). There was no significant difference in the two groups.

Discussion/ Conclusion: Few studies stated that BRCA1 mutation may be associated with reduced ovarian reserve in healthy BRCA mutation carriers. Meirow and al concluded that both healthy and BC BRCA mutation carriers demonstrated normal ovarian response in vitro fertilization cycles. Our results show that ovarian reserve of BRCA 1/2 mutations BC carriers do not differ from that of non-carriers. Response to COH seems similar in both groups too.

Citation Format: Mailliez A, Keller L, Menu-Hespel S, Plouvier P, D'Orazio E, Basson L, Pigny P, Bonneterre J, Decanter C. Ovarian reserve and response to controlled ovarian hyperstimulation (COH) in breast cancer women with and without BRCA mutation [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-09-06.