Abstract OT2-01-08: POSITIVE: A study evaluating pregnancy and disease outcome and safety of interrupting endocrine therapy for young women with endocrine responsive breast cancer who desire pregnancy (IBCSG 48-14/BIG 8-13)
Authors: Pagani O , Partridge A , Azim HA , Peccatori FA , Ruggeri M , Sun Z 
Published: May 2016

Abstract
Background
Young breast cancer (BC) patients often face the disease before completing their family planning. The best available retrospective evidence suggests that pregnancy after BC does not negatively impact disease outcome in patients with endocrine sensitive BC and is safe for the offspring. However, given the need for prolonged adjuvant endocrine therapy for 5-10 years, it is not feasible to wait until completion of therapy in most of these women and thus there is a need to explore the safety of temporary interruption of endocrine therapy to allow pregnancy. To date, no definitive prospective study has been conducted in young women desiring future pregnancy.
Trial Design
Young patients with endocrine responsive early BC and pregnancy desire will interrupt endocrine treatment 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), breast feeding (∼6 mos). Patients will be strongly advised to resume ET as soon as pregnancy attempts are concluded, and to complete 5-10 yrs ET at the local investigator discretion.
Major Eligibility Criteria
-Histologically-proven stage I-III endocrine-responsive BC.
-Age ≥ 18 and ≤ 42 years at enrollment.
-Adjuvant endocrine therapy (SERM alone, GnRH analogue plus SERM or AI) for ≥18 months but ≤30 months, stopped within 1 month prior to enrollment.
-Patient wishes to become pregnant.
-Premenopausal status at BC diagnosis.
Specific Aim
To assess the risk of BC relapse associated with temporary interruption of ET to permit pregnancy and to evaluate pregnancy success.
Statistical Methods
A true risk of BC recurrence of 2% per year is assumed for patients who do not interrupt endocrine treatment. With 500 patients enrolled in 4.0 yrs and an additional 1.6 yrs of follow up, there will be approximately 1600 patient-yrs of follow up and a median follow up of approximately 3 yrs at the time of the primary analysis, anticipated to occur 5.6 yrs after enrollment of the first patient. If the true risk of BC recurrence is 2% per yr, we anticipate 31 BC recurrences and an estimated 3-yr breast cancer free interval (BCFI) failure of 5.6% (95% CI 4.0% to 7.9%).
Translational Research will investigate different ovarian function parameters; uterine evaluation; and circulating tumor DNA. FFPE tissue of the primary tumor will be collected to integrate different parameters related to biology of BC arising in young women. All material will be banked centrally.
Psycho-oncological Companion Study on fertility concerns, psychological well-being and decisional conflicts is mandatory in the United States and open to interested centers elsewhere.
Accrual: Target: 500; Actual: 4 (31 May 2015)
Contact Information
POSITIVE is conducted and sponsored by the International Breast Cancer Study Group. Alliance for Clinical Trials in Oncology is US sponsor for NCTN network. Contact Trial Coordinators at ibcsg48_positive@fstrf.org.
Citation Format: Pagani O, Partridge A, Azim Jr HA, Peccatori FA, Ruggeri M, Sun Z. POSITIVE: A study evaluating pregnancy and disease outcome and safety of interrupting endocrine therapy for young women with endocrine responsive breast cancer who desire pregnancy (IBCSG 48-14/BIG 8-13). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT2-01-08.