Preclinical evidence suggests a possible negative impact of germline BRCA mutations on female fertility. However, the reproductive potential and performance of fertility-preserving procedures in BRCA+ BC pts remain largely uncertain. We aimed to assess fertility outcomes in BRCA+ BC pts who underwent oocyte cryopreservation (OC) or ovarian tissue cryopreservation (OTC) before (neo)adjuvant chemotherapy.
This was a retrospective analysis of two prospective single center studies investigating OC and OTC in early BC pts. The present analysis included known BRCA+ or BRCA mutation-negative (BRCA-) BC pts who underwent OC or OTC between January 2006 and December 2016. Pts with unknown BRCA status, BRCA variants of unknown significance or other germline mutations were excluded. Baseline anti-mullerian hormone (AMH), OC and OTC performance were compared between BRCA+ and BRCA- BC pts.
Out of 98 pts included in this analysis, 29 were BRCA+ and 69 BRCA-. Median age was 31 (range: 29-33) and 30 (range: 28-33) years in BRCA+ and BRCA- BC pts, respectively. Baseline AMH was 1.8 ng/ml (range: 1-2.7) in BRCA+ and 2.6 ng/ml (range: 1.4-4.3) in BRCA- BC pts (p = 0.108). Among pts who underwent OC (n = 27), despite receiving a numerically higher dose of gonadotropins (2775 vs 2150 UI; p = 0.125) and longer duration of stimulation (11.5 vs 9; p = 0.164), BRCA+ pts tended to retrieve (6.5 vs. 10; p = 0.135) and to cryopreserve (3.5 vs 6; p = 0.134) less oocytes than BRCA- pts. Poor response rate (i.e. retrieval of ≤ 4 oocytes) was 40% in BRCA+ and 12.5% in BRCA- BC pts (p = 0.105). Among pts who underwent OTC (n = 71), BRCA+ pts had numerically lower oocyte density per fragment (0.08 vs 0.14; p = 0.224) and per mm2 (0.33 vs 0.75; p = 0.160) than BRCA- pts. Two BRCA+ pts were transplanted after chemotherapy and one delivered at term a healthy baby. No difference between BRCA1+ and BRCA2+ pts was observed in any of the above-mentioned outcomes.
This is the largest study addressing fertility issues in BRCA+ BC pts. We observed a trend for reduced reproductive potential and performance of OC and OTC in BRCA+ BC pts. Further research efforts in this field are urgently needed.
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E. De Azambuja, M. Ignatiadis: Honoraria from Roche and travel grants from Roche and GlaxoSmithKline outside the submitted work. All other authors have declared no conflicts of interest.