The POSITIVE trial previously demonstrated the safety and feasibility of temporarily interrupting adjuvant endocrine therapy (ET) to allow for pregnancy in women with hormone receptor (HR)-positive early breast cancer. With early follow-up (median, 41 months), the trial showed that this approach did not increase breast cancer recurrence risk. The POSITIVE trial’s 5-year follow-up revealed that temporary interruption of ET for pregnancy in women with early-stage, HR-positive breast cancer did not lead to an increased risk of breast cancer recurrence.

POSITIVE (NCT02308085) is a single-arm, prospective trial that enrolled 518 eligible women with HR-positive, stage I-III breast cancer wishing to become pregnant between December 2014 and December 2019. Participants were permitted to interrupt adjuvant ET after 18 to 30 months for up to 2 years to attempt pregnancy. Outcomes were compared with a matched external control group of patients from the SOFT/TEXT trials. Five-year breast cancer–free interval (BCFI) and distant recurrence-free interval (DRFI) event rates were estimated for both groups, as well as pregnancy and in vitro fertilization outcomes, and ET resumption rates.

A total of 516 patients were evaluable for breast cancer–related events and 497 were evaluable for pregnancy-related events. At the time of enrollment, of 516 patients, 43% were aged 35 to 39 years, 75% had no prior births, the majority were early breast cancer stage I-II, and 62% had prior (neo-)adjuvant chemotherapy. At a median follow-up of 71 months in the POSITIVE cohort and 80 months in the SOFT/TEXT external control cohorts, the 5-year cumulative incidence of BCFI events was 12.3% in the POSITIVE cohort compared with 13.2% in SOFT/TEXT, resulting in a difference of −0.9% (95% confidence interval [CI], −4.2% to 2.6%). The 5-year cumulative incidence of DRFI events was 6.2% in the POSITIVE cohort and 8.3% in SOFT/TEXT, with a difference of −2.1% (95% CI, −4.5% to 0.4%). Of the 382 HER2-negative patients, the 5-year cumulative incidence of BCFI events was 14.1% in the POSITIVE cohort compared with 13.1% in SOFT/TEXT, resulting in a difference of 1.0% (95% CI, −3.2% to 5.2%). The 5-year cumulative incidence of DRFI events was 6.8% in the POSITIVE cohort and 7.9% in SOFT/TEXT, with a difference of −1.1% (95% CI, −4.0% to 1.9%).

At a 71-month median follow-up, of the 497 women followed for pregnancy outcomes, 377 (76%) achieved at least 1 pregnancy during the trial (of 589 pregnancies), and 343 (91%) had at least 1 live birth, 79 patients had a least 2, and 4 patients had at least 3 live births. The most frequent complication of pregnancy was hypertension (2.5%). A total of 8.6% of offspring had low birth weight and 1.6% had birth defects similar to women who did not have a previous breast cancer diagnosis. An 18-month landmark analysis using a multivariable time-dependent Cox analysis included age, body mass index, lymph node status, prior chemotherapy, and prior aromatase inhibitors. This analysis showed that of the 456 patients who were followed and disease-free for 18 months, no significant differences in BCFI events were found between women who had a pregnancy and those who did not at 5 years from enrollment, with a hazard ratio of 0.65 (95% CI, 0.37-1.14). Within this analysis, among 180 women (36%) who underwent embryo or oocyte cryopreservation prior to enrollment, the 5-year cumulative incidence of BCFI events was 14.0% (95% CI, 9.6%-20.2%), compared with 11.5% (95% CI, 8.4%-15.7%) in those who did not undergo cryopreservation with a hazard ratio of 1.35 (95% CI, 0.83-2.21). Of the 429 patients who remained disease-free for at least 2 years, 352 (82%) resumed ET as per protocol.

Temporary interruption of adjuvant ET for pregnancy in young women with HR-positive early breast cancer does not appear to increase the risk of breast cancer recurrence at 5 years. A high proportion of women achieved at least 1 live birth, and the majority resumed ET following the interruption. These findings provide further reassurance to young breast cancer survivors considering pregnancy. Ongoing follow-up will be important to assess longer-term outcomes and provide additional guidance for clinical practice.

Source: Peccatori FA, Pagani O, Niman SM, et al. 5-year follow-up results from the POSITIVE (Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer) trial. Presented at: ESMO Congress 2025. October 17, 2025; Berlin, Germany. Abstract LBA 12.