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Impact of assisted reproductive technologies and new therapeutic regimens on fertility and oncological outcomes in young breast cancer patients

par Condorelli, Margherita
Président du jury Casimir, Georges
Promoteur Demeestere, Isabelle
Publication Non publié, 2023-09-05

Thèse de doctorat

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Résumé :

Pregnancy after treatment for breast cancer (BC) does not impact prognosis but young cancer survivors have low chances of becoming mothers. As cancer treatment can hinder fertility, artificial reproductive technologies (ART), using either fresh gametes after ovarian stimulation or gametes that were cryopreserved prior to gonadotoxic treatment may be required to become pregnant. For those bearing a deleterious BRCA germline mutation, which increases the risk of breast and ovarian cancer, these challenges can be amplified due to defects in DNA repair pathways. The objectives of this thesis were to evaluate 1/ the impact of ART on BC survivors, including those who are carriers of a BRCA mutation, 2/ the impact of ionizing radiation exposure from medical imaging, for BC stage and risk assessment, on oocyte quality during ovarian stimulation for fertility preservation (FP). We have conducted three clinical trials. The first, the ACCESS study, was a retrospective multicentric matched cohort (1:2) study addressing the impact of ART after BC. BC survivors who underwent ART between January 2006 and December 2016 (n=39) and matched BC survivors (n=73) were selected from eight Belgian fertility clinics and two oncological centers. After a median follow-up time of >4 years, similar oncological outcomes were observed, irrespective of ART cycle after treatment for BC.Second, the BRCA ART study was a retrospective, international, multicenter study (NCT02308085) that specifically addressed the impact of ART in BRCA-mutated survivors. BC survivors with BRCA1/2 mutations diagnosed between January 2000 and December 2012 were included and those who were pregnant after ART (n=22) were compared to those who achieved spontaneous pregnancies (n=146). Oncological outcomes were similar at >3 years of follow-up, although ART-exposed patients were older at diagnosis with more favorable disease features than non-ART exposed patients. Finally, the CARLOTA study evaluated ionizing radiation-related risk on oocyte quality. This retrospective study included all BC patients who underwent ovarian stimulation for FP between November 2012 and May 2020. We compared the oocyte collection and maturation outcomes between patients with ionizing radiation exposure (IRE) for their BC stage and risk assessment during ovarian stimulation (n=14), and those without any IRE during ovarian stimulation (n=60). This study demonstrated that IRE during ovarian stimulation did not affect oocyte collection and maturation rates.In conclusion, studies associated with this thesis demonstrated that BC survivors can be safely treated with ART, including women who carry a deleterious BRCA germline mutation. Ovarian stimulation for FP during BC stage and risk assessment does not impair oocyte maturation rates.