Interrupting adjuvant endocrine therapy to attempt pregnancy does not increase the risk of breast cancer recurrence or new contralateral breast cancer in patients with early-stage, hormone receptor (HR)-positive breast cancer, according to results from the POSITIVE trial published in The New England Journal of Medicine.
Patients in this trial had received adjuvant endocrine therapy for at least 18 months prior to interruption and had a 3-month washout period prior to attempting pregnancy. The interruption was allowed for up to 2 years, during which patients could attempt pregnancy and breastfeed if desired and feasible.
The POSITIVE trial (ClinicalTrials.gov Identifier: NCT02308085) included 516 patients with stage I-III, HR-positive breast cancer. At baseline, the patients’ median age was 37 years, and the median time from breast cancer diagnosis to enrollment was 29 months. Most patients (93.4%) had stage I or II disease, 62.0% had received chemotherapy, 29.3% had 1-3 positive nodes, and 4.5% had 4-9 positive nodes.
The researchers compared these patients to an external control cohort of 1499 patients from the SOFT and TEXT trials who met the eligibility criteria for the POSITIVE trial and were treated with adjuvant endocrine therapy.
At a median follow-up of 41 months, 86.1% of the POSITIVE cohort had a live birth, including full-term (79.3%) or pre-term (7.3%). Assisted reproductive technology was used in 43.3% of pregnancies. Among the 368 patients with at least 1 pregnancy, 25.3% had a miscarriage, 4.3% had an elective abortion, 0.3% had a stillbirth, and 0.3% had a neonatal death. Among the 317 patients with at least 1 live birth, 61.8% engaged in breastfeeding.
The study’s primary endpoint was the number of breast cancer events, which included local, regional, or distant recurrence and new contralateral invasive breast cancer. The researchers used a bootstrap matching method to compare outcomes in the POSITIVE cohort and the control cohort. The researchers averaged results from 5000 bootstrap samples that were matched by age, body mass index, number of positive lymph nodes, previous chemotherapy, and previous use of an aromatase inhibitor.
The 3-year incidence of breast cancer events was 8.9% in the POSITIVE cohort and 9.2% in the control cohort (adjusted hazard ratio [aHR], 0.81; 95% CI, 0.57-1.15). The 3-year incidence of distant breast cancer recurrence was 4.5% in the POSITIVE cohort and 5.8% in the control cohort (aHR, 0.70; 95% CI, 0.44-1.12).
Of the POSITIVE patients who remained disease-free during treatment interruption, 73.3% resumed endocrine therapy. Most of the patients who had not restarted treatment at last follow-up were continuing to attempt pregnancy, were currently or recently pregnant, or were actively or recently breastfeeding.
“The POSITIVE trial showed no clear worsening of breast cancer outcomes in the short term after temporary interruption of endocrine therapy to allow for pregnancy,” the researchers concluded. “Longer-term follow-up is needed to further inform the safety of this strategy.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Partridge AH, Niman SM, Ruggeri M, et al. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. Published online May 4, 2023. doi:10.1056/NEJMoa2212856