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Aims: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) represent a standard of care for the clinical management of high-grade serous ovarian cancer (HGSOC). The recognition of homologous recombination deficiency (HRD) has emerged as a predictive biomarker of response for first-line PARPIs treatment in patients with HGOSC. On the other hand, this test is extremely complex and therefore it is often externalised. Regrettably, the reliability of outsourced HRD testing can be troubled by inconclusive results and high rejection rates. In this methodological study, we assessed the technical feasibility, interassay and interlaboratory reproducibility of in-house HRD testing using three different commercially available next-generation sequencing assays., Methods: A total of n=20 epithelial ovarian cancer samples previously analysed with MyChoice CDx were subjected to HRD retesting using three different platforms in three different major pathology laboratories, that is, SOPHiA DDM HRD Solution, HRD focus and Oncomine homologous recombination repair pathway predesigned panel. Concordance was calculated by Cohen's (dual) and Fleiss (triple) κ coefficients., Results: In-house BRCA1/2 molecular testing yielded a concordance rate >90.0% among all participating centres. HRD scores were successfully calculated by each institution with a concordance rate of 76.5%. Concerning the external gold standard test, the overall percentage of agreement ranged from 80.0% to 90.0% with a positive percentage agreement ranging from 75.0% to 80.0% and a negative percentage agreement ranging from 80.0% to 100%., Conclusions: In-house testing for HRD can be reliably performed with commercially available next-generation sequencing assays., Competing Interests: Competing interests: EG-R has relevant relationship (advisory fees, honoraria, travel accommodation and expenses, grants and non-financial support) with AstraZeneca, Exact Sciences, GlaxoSmithKline (GSK), Novartis, Roche, Thermo Fisher Scientific unrelated to the current work. MF reports research funding (to Institution) from QED, Macrophage pharma, Astellas, Diaceutics; personal honoraria as invited speaker from Roche, Astellas, AstraZeneca, Incyte, Bristol Myers Squibb (BMS), Merck Serono, Pierre Fabre, GSK, Novartis, Amgen; participation in advisory board for Amgen, Astellas, Roche, Merck Serono, GSK, Novartis, Janssen unrelated to the current work. NF reports honoraria from Merck Sharp and Dohme (MSD), Boehringer Ingelheim, Novartis, AstraZeneca and Daiichi Sankyo unrelated to the current work. CDA Consulting/Advisor: Roche, AstraZeneca, Lilly, GSK, Novartis, Pfizer, Seagen Honoraria: Novartis, Pfizer, Lilly. Research funding to the institution: Novartis, Daiichi Sankyo. Travel, accommodation, expenses: Roche, AstraZeneca, Lilly, GSK, Novartis, Celgene, Pfizer unrelated to the current work. GV reports speaking honoraria from PharmaMar, AstraZeneca, Roche, Clovis and GSK-Tesaro and travel grants from GSK-Tesaro and PharmaMar and has been part of the advisory boards of Tesaro, Amgen and PharmaMar outside of the submitted work. UM has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientific, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, Janssen, Diatech, Novartis and Hedera unrelated to the current work. GT reports personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen and Bayer, unrelated to the current work. MB has received honoraria for consulting, advisory role, speakers’ bureau, travel, accommodation, expenses from MSD Oncology, Roche/Genetech, AstraZeneca, Thermo Fisher Scientific, GSK and Illumina unrelated to the current work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In reproductive medicine the widespread use of ovarian stimulation has focused interest on the possible relation between induction of ovulation and breast and ovarian cancer. The epidemiological studies published so far are reassuring but not devoid of methodological problems, such as small populations, short follow-ups, and lack of information on confounding factors like oral contraceptive use. In younger patients to preserve fertility before radio- or chemotherapy, the American Society of Clinical Oncology recommended embryo cryopreservation as an established procedure. Moreover, experimental procedure as oocytes cryopreservation, ovarian suppression with GnRH analogues and cortical ovarian tissue freezing probably will be routinely used in the future. A reasonable proposal to protect patients from the risk of estrogen peaks in the case of estrogen receptor positive (ER+) breast cancer, ovarian stimulation with tamoxifen or letrozole could be right. Powered studies are necessary to control the safety and effectiveness of the different fertility preservation options. In this review we evaluated the relation between induction of ovulation and breast and ovarian cancer and then the possible options for fertility preservation in patients with these types of tumors.