Abstract OT3-02-01: 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 AH , Azim HA , Peccatori F , Ruggeri M , Sun Z 
Published: March 2017

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 outcomes in patients with endocrine-responsive BC and is safe for offspring. However, given the possibility of prolonged adjuvant endocrine therapy (ET) (5-10 yrs), it is not feasible to wait until completion of therapy in many of these women and thus there is a need to explore the safety of temporary interruption of ET to allow pregnancy. To date, no prospective study has been conducted in young women attempting future pregnancy.
Trial Design
Young patients with endocrine-responsive early BC and pregnancy desire 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), breast feeding (∼6 mos). Patients will be strongly advised to resume ET as soon as pregnancy attempts are concluded and to complete the planned 5-10 yrs ET.
Major Eligibility Criteria
* Histologically-proven stage I-III endocrine-responsive BC.
* Age ≥ 18 and ≤ 42 years at enrollment.
* Adjuvant ET (SERM alone, GnRH analogue plus SERM or AI) for ≥18 mos but ≤30 mos, stopped within 1 mo 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 and offspring outcome.
Statistical Methods
A true risk of BC recurrence of 2% per year is assumed for patients who do not interrupt ET. 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 enrolment 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) event of 5.6% (95% CI 4.0% to 7.9%).
Translational Research will investigate different ovarian function and uterine parameters; and circulating tumour DNA. FFPE tissue of the primary tumour 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 US and open to interested centers elsewhere.
Accrual: Target: 500; Actual: 39 (30 Apr 2016)
Psycho-oncological Companion Study Accrual: Target: 200; Actual: 29 (30 Apr 2016)
Contact Information
POSITIVE is conducted and sponsored by the International Breast Cancer Study Group. The Alliance for Clinical Trials in Oncology is the US sponsor for NCTN network. Contact Monica Ruggeri, IBCSG Coordinating Center, monica.ruggeri@ibcsg.org, or Trial Coordinators at ibcsg48_positive@fstrf.org.
Citation Format: Pagani O, Partridge AH, Azim Jr. HA, Peccatori F, 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 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-02-01.