Balancing Fertility Preservation and Treatment Efficacy in (Neo)adjuvant Therapy for Adolescent and Young Adult Breast Cancer Patients: a Narrative Review

Adolescent and young adult (AYA) breast cancer survivors face a significant risk of infertility due to the gonadotoxic effects of (neo)adjuvant therapy, which complicates their ability to conceive post-treatment. While (neo)adjuvant therapy primarily aims to improve recurrence-free and overall survival, fertility preservation strategies should also be considered for young patients. This narrative review explores recent advancements in fertility preservation techniques, such as oocyte, embryo, and ovarian tissue cryopreservation, and evaluates the feasibility of modifying breast cancer (neo)adjuvant therapy to preserve fertility without compromising survival outcomes.

Our review highlights that clinical trials with co-primary endpoints of oncological safety and fertility preservation are limited, and substituting standard treatment regimens solely for fertility preservation is currently not recommended. Nevertheless, new clinical studies have emerged that either exclude highly ovarian-toxic agents, such as cyclophosphamide, or omit adjuvant therapy altogether, even if fertility preservation is not their primary endpoint. Unfortunately, many of these trials have not evaluated ovarian toxicity. Notably, since 2020, major oncology organizations, including the American Society of Clinical Oncology (ASCO), the European Society of Medical Oncology (ESMO) have advocated for the routine assessment of ovarian toxicity in all clinical trials.

The review underscores the importance of incorporating ovarian toxicity as a standard endpoint in future trials involving premenopausal breast cancer patients to identify treatment regimens that can effectively balance fertility preservation with treatment efficacy.