Background Young patients with breast cancer (BC) are often diagnosed with the disease before completing their families. The best available retrospective evidence suggests that pregnancy after BC does not negatively impact disease outcomes in patients with endocrine responsive BC and is safe for the offspring. However, given the possibility of extended adjuvant endocrine therapy (ET) (5-10 years), it is not feasible for many of these women to delay pregnancy until completion of therapy and thus there is a need to study the safety of interrupting ET to allow pregnancy. To date, no prospective study has been conducted in BC survivors attempting future pregnancy. Trial Design Young patients with endocrine responsive early BC who desire pregnancy will interrupt ET for up to 2 yrs to attempt pregnancy. As resumption of menses and conception depends on many factors (e.g. patient's age and adjuvant treatment received), the 2-yr interruption period is approximate, intended to include treatment wash-out (3 mos), conception (˜3-6 mos), delivery (˜9 mos), and breast feeding (˜6 mos). Patients will be strongly advised to resume ET as soon as pregnancy attempts/deliveries are concluded, and to complete the planned 5-10 yrs of ET. Major Eligibility Criteria - Histologically-proven stage I-III endocrine-responsive BC. - Patient's wish to become pregnant. - Age ≥ 18 and ≤ 42 years at enrollment. - Adjuvant ET (selective estrogen receptor modulator [SERM] alone, GnRH analogue plus SERM or aromatase inhibitor) for ≥18 months but ≤30 months, stopped within 1 month prior to enrollment. - Premenopausal status at BC diagnosis. Specific Aim To assess the risk of BC relapse associated with the interruption of ET to permit pregnancy, and to evaluate pregnancy success rate and offspring outcome. Statistical Methods With 500 pts enrolled and followed for a median of 3 years, the statistical design is based on the 95% CI for the 3-year BC recurrence rate. Interim monitoring assumes a 2% BC recurrence risk/yr with continuous ET and a recommendation to stop the study early if the BC risk exceeds 4%/yr with ET interruption. Translational Research will investigate various ovarian function and uterine parameters and circulating tumour DNA. Fresh frozen paraffin embedded tissue of the primary tumour will be collected to evaluate parameters related to the biology of BC in young women. All material will be banked centrally. Psycho-oncological Companion Study (POCS) will evaluate fertility concerns, psychological well-being and decisional conflict. It is mandatory in North America and open to interested centers elsewhere. Accrual: Target: 500; Actual: 262 (30 June 2018) Psycho-oncological Companion Study Accrual: Target: 200; Actual: 138 (30 June 2018) Citation Format: Pagani O, Partridge AH, Peccatori F, Azim HA, Colleoni M, Saura C, Kroep JR, Warner E, Gombos A, Sætersdal AB, Ruggeri M, Gelber RD, Sun Z. POSITIVE: A study evaluating Pregnancy, disease outcome and safety of interrupting endocrine therapy for premenopausal women with endocrine responsIVE breast cancer who desire pregnancy (IBCSG 48-14/BIG 8-13) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-01-06.