Abstract Many young women have not completed their desired childbearing when they are diagnosed with breast cancer. This is increasingly true as the average age of first birth rises such that more premenopausal breast cancers are diagnosed in nulliparous women. Even women who already have one or more children at the time of their cancer diagnosis may be hoping to become pregnant again. Because chemotherapy is gonadotoxic and endocrine therapy is contraindicated during pregnancy(allowing natural ovarian aging over the 5-10 years of adjuvant therapy recommended for those with endocrine-sensitive stage 1-3 tumors), breast cancer treatments can impair fertility. Fertility preservation strategies including oocyte cryopreservation and embryo cryopreservation should be considered prior to initiation of systemic therapy for young women with fertility concerns, often using modified ovarian stimulation protocols to minimize delays in cancer treatment. The administration of a gonadotropin-releasing hormone agonist before and during chemotherapy to help maintain ovarian function is more controversial, but can also be considered. It is critical that we offer reproductive counseling and access to fertility preservation techniques at the time of diagnosis, and that we also continue to discuss contraception and fertility planning during and after cancer treatment. Results from the POSITIVE trial, which is assessing pregnancy and cancer outcomes of young women who wished to take a break from adjuvant endocrine therapy to attempt conception, are eagerly awaited to inform these discussions. This talk will address current knowns and unknowns related to the optimal management of reproductive concerns in premenopausal women with breast cancer. Citation Format: K Ruddy. Oncofertility [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP133.