At SABCS, Ann Partridge, MD, presented initial results from the international Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine responsIVE breast cancer (POSITIVE) Trial (IBCSG 48-14/BIG 8-13), a prospective, single arm trial determining the effect of temporarily interrupting endocrine therapy (ET) to attempt pregnancy on breast cancer (BC) recurrence.
POSITIVE enrolled premenopausal women desiring pregnancy who were age ≤42 years, with >18 and <30 months of prior adjuvant ET for stage I-III hormone receptor (HR)+ BC with no recurrence.
ET was interrupted ≤1 month of enrollment for up to 2 years to attempt pregnancy, conceive, deliver, and breastfeed, after a 3-month washout. Fertility assessment was recommended if no pregnancy by 1 year. ET resumption was strongly recommended after pregnancy to complete the planned 5-10 years of treatment. The primary efficacy endpoint is BC-free interval (FI) from enrollment to first recurrence (n=516).
At a median follow-up of 41 months, BCFI was 8.9% and distant recurrence-FI was 4.5%. These outcomes are not statistically significantly different from cohorts of 1499 patients from the SOFT and TEXT trials used as external controls. There were no differences in BCFI between patients in the POSITIVE trial who did or did not become pregnant, indicating temporary interruption of ET to attempt pregnancy does not impact short-term disease outcome.
Of 497 patients in the secondary endpoint population, 74% (n=368) had ≥1 pregnancy (70% within 2 years), for a total of 507 pregnancies which resulted in ≥1 live birth (64% of total; 86% of pregnancies); 19% had ≥1 miscarriage. Pregnancy complications occurred in 11%. There were 335 singleton births and 15 sets of twins for the 317 women who had ≥1 live birth; 62% reported breastfeeding. Birth defects were low and not clearly associated with treatment exposure.
Long-term follow-up is ongoing to at least 2029 to monitor ET resumption and outcomes.
Discussant Jennifer K. Litton, MD, said POSITIVE, as the first trial to answer this difficult question, looks at the safety of a practice that was already happening. Although POSITIVE was a single arm study compared with an historic control, this question can never be studied in a randomized controlled trial. Pregnancy after BC is a personal decision; progress in discussing fertility concerns with patients who want future pregnancies is needed.
Dr. Lederman has no conflicts of interest to report.
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