Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer
- Study type
- Clinical trial
- Study name
- POSITIVE
- Design
- Single-group trial with comparison against an external control cohort
- Sample size
- 516 women
- Source
- N Engl J Med · 2023
- Trial registration
- NCT02308085
In plain words
This study looked at whether young women who had hormone-sensitive breast cancer could pause their hormone treatment for a while to try to become pregnant. About three quarters of the women had at least one pregnancy, and nearly two thirds had at least one live baby. Over about three years, the risk of the cancer coming back was no higher in these women than in a comparison group, but longer follow-up is needed to be sure it is safe in the long term.
Key results
Treatment arms and regimens
Strategic intervention without a drug: adjuvant endocrine therapy stopped in the month before enrolment; a 3-month washout period before attempting pregnancy; treatment break of up to 2 years for attempting pregnancy, conception (or failure to conceive), delivery and breastfeeding. Assisted reproduction was allowed, and fertility assessment was strongly recommended if no pregnancy occurred after 1 year. After the end of pregnancy and breastfeeding, or failure to conceive, resuming endocrine therapy to complete the planned 5 to 10 years of treatment was strongly recommended.
Non-randomised external control cohort: 1499 patients from the SOFT and TEXT trials who met the POSITIVE eligibility criteria and received adjuvant endocrine therapy in those trials. The main comparison used bootstrap matching on age, body mass index, number of positive lymph nodes, prior chemotherapy and prior aromatase inhibitor use.
Source of the regimen details: Full text of the paper (PMC10358451); strategic intervention (temporary interruption of endocrine therapy), no drug dose
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Women aged 42 or younger with a history of stage I, II or III hormone receptor-positive breast cancer (threshold 1% or more; local testing) who had received 18 to 30 months of adjuvant endocrine therapy, had no clinical evidence of recurrence and wished to interrupt treatment temporarily to attempt pregnancy; prior chemotherapy (with or without fertility preservation) was allowed. Median age 37 years (34.3% younger than 35), median time from diagnosis to enrolment 29 months, 93.4% stage I or II, 29.3% with 1 to 3 and 4.5% with 4 to 9 positive lymph nodes, and 62.0% with prior chemotherapy.
Endpoints
Primary endpoint: number of breast cancer events (local, regional or distant recurrence of invasive breast cancer, or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned after 1600 patient-years of follow-up, and the prespecified safety threshold was 46 breast cancer events in that period.
Safety and side effects
Graded drug toxicities were not reported in the primary report; the main safety outcome was breast cancer events: 44 events (within the prespecified threshold of 46 events); 3-year incidence 8.9% versus 9.2% in the external control cohort. Pregnancy complications occurred in 41 women (11.1% of the 368 who became pregnant): hypertension or pre-eclampsia 3.8%, diabetes 2.4% and placental abnormalities 1.6%. Low birth weight (less than 2500 g) in 29 infants (7.9%) and birth defects in 8 infants (2.2%).
Clinical significance and place in guidelines
Based on the abstract, temporary interruption of endocrine therapy to attempt pregnancy in selected women with hormone receptor-positive early breast cancer was not associated with a higher short-term risk of breast cancer events. Decisions should be individualised and made with the treating team, and long-term follow-up is needed. The status of this finding in clinical guidelines should be checked separately.
Limitations
Single-group trial compared with an external control cohort. Median follow-up was 41 months, and the authors stress that longer follow-up is critical to establish long-term safety. The findings apply to selected women.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.