POSITIVE Trial Demonstrates Safe Breastfeeding During Endocrine Therapy Break for HR+ Breast Cancer Patients
Key Insights
The POSITIVE trial showed that breastfeeding is feasible for young patients with hormone receptor-positive breast cancer (search) who conceived during a planned interruption of endocrine therapy (search), with a median breastfeeding duration of 4.4 months.
Among 196 patients who breastfed, breast cancer (search) recurrence rates remained low at 1.1% at 12 months and 3.6% at 24 months, comparable to those who did not breastfeed.
The study represents the largest prospective evaluation of breastfeeding patterns in young HR-positive breast cancer (search) survivors, supporting the incorporation of breastfeeding counseling into individualized patient care.
Young women with hormone receptor-positive breast cancer (search) can safely breastfeed during planned interruptions of endocrine therapy (search), according to follow-up findings from the POSITIVE trial presented at the 2024 European Society of Medical Oncology (ESMO) Congress. The study provides the first comprehensive prospective data on breastfeeding feasibility and safety in this patient population.
Breastfeeding Patterns and Duration
Among the 196 patients who breastfed in the study, the median duration of breastfeeding for the first child was 4.4 months (95% CI, 4.0-5.3). Notably, 37.1% of patients breastfed for 6 months or more, 12.8% continued for 12 months or more, and 1.5% breastfed for 24 months or more. All patients were required to restart endocrine therapy (search) treatment within 2 years of the interruption.
The study revealed interesting patterns based on surgical history. Of the 196 patients who breastfed, 66.3% had undergone conservative surgery, with the majority (69.2%) breastfeeding from the contralateral breast only, 29.2% from both breasts, and 1.5% from the affected breast. The remaining 33.6% had undergone unilateral surgery.
Safety Profile and Recurrence Rates
At a median follow-up of 41 months, the safety data proved reassuring. The rate of first invasive tumor recurrence (BCFI) at 12 months was 1.1% (95% CI, 0.3%-4.4%) in patients who breastfed compared to 1.9% (95% CI, 0.5%-7.5%) in those who did not. At 24 months, the BCFI rate was 3.6% (95% CI, 1.5%-8.8%) in the breastfeeding group versus 3.1% (95% CI, 1.0%-9.5%) in the non-breastfeeding group.
"This is the largest prospective evaluation of breastfeeding frequency, pattern, and impact on BCFI in a cohort of young patients with HR-positive early breast cancer (search)," said Fedro Peccatori, MD, PhD, director of the Fertility and Procreation Unity in the Division of Gynecologic Oncology at the European Institute of Oncology (search) in Milan, Italy. "These data underline the interest of young breast cancer survivors in breastfeeding and reinforce the notion that breastfeeding counseling should be incorporated into their individualized support."
POSITIVE Trial Design and Outcomes
The POSITIVE trial enrolled 518 patients aged 42 years or younger with HR-positive, stage I to III breast cancer (search) who desired pregnancy. Conducted as a single-arm prospective trial from December 2014 to December 2019, the study allowed patients to interrupt their adjuvant endocrine therapy (search) after 18 to 30 months of treatment.
Following enrollment within one month of stopping treatment, patients underwent a 3-month washout period before proceeding with up to a 2-year break to allow for conception, delivery, and potentially breastfeeding. After the 2-year period, patients resumed endocrine therapy (search) and continued follow-up for up to 10 years.
Pregnancy and Birth Outcomes
The trial demonstrated encouraging pregnancy outcomes. Among the 317 patients with live births, pregnancy status was reported in 497 patients, with 74.0% becoming pregnant at least once during the trial. Successful pregnancies were observed in 85.7% of patients younger than 35 compared to 76.0% for those aged 35 to 39 years. Overall, 43.3% of patients used assisted reproductive technology during the trial.
As of the database lock, 63.8% of patients had a live birth, and 86.1% had at least one pregnancy. Pregnancy complications were relatively uncommon, with hypertension or preeclampsia occurring in 3.8% of patients, diabetes mellitus in 2.4%, and placental abnormalities in 1.6%. Among babies born, 7.9% had low birth weights and 2.9% had birth defects.
Long-term Safety Data
The overall safety profile of the treatment interruption strategy remained favorable. During the study, 44 patients had their treatment interrupted due to a breast cancer (search) event, which was within the pre-specified safety threshold of 46 events. The 3-year incidence of breast cancer was 8.9% (95% CI, 6.3%-11.6%) for those who interrupted their treatment versus 9.2% (95% CI, 7.6%-10.8%) in the control cohort.
The 3-year incidence rate for distant recurrence in the interruption group was 4.5% (95% CI, 2.7%-6.4%) compared to 5.8% (95% CI, 4.5%-7.2%) in the control group. A multivariate Cox model determined the hazard ratio for breast cancer (search) events associated with pregnancy was 0.53 (95% CI, 0.27-1.04).
Clinical Implications
The findings have significant implications for clinical practice and patient counseling. "I think POSITIVE will open the door for more young women to say, 'I can take a break and try to become pregnant'. At least in the short term, it appears safe. Hopefully, in the long term, we'll have data that appear safe from a prospective standpoint," noted Anna H. Partridge, MD, MPH, vice chair of Medical Oncology and founder and director of the Program for Young Adults with Breast Cancer (search) at Dana-Farber Cancer Institute.
The study's comprehensive data on breastfeeding patterns and safety outcomes provides healthcare providers with evidence-based information to support young breast cancer (search) survivors in making informed decisions about family planning and breastfeeding during their cancer treatment journey.