Younger Age Improves Pregnancy Prospects After ET Therapy Pause in HR+ Breast Cancer

Updated results from the POSITIVE trial found that patients younger than 35 years had a higher likelihood of achieving pregnancy during an endocrine therapy pause for HR-positive breast cancer.

Patients with hormone receptor–positive breast cancer who are premenopausal and interrupted endocrine therapy to attempt pregnancy and who were of younger age were one determinant of shorter time to pregnancy, according to the prespecified secondary analysis of the POSITIVE trial (NCT02308085).^1,2

For patients younger than 35 years, the cumulative incidence of pregnancy by year 1 was 63.5%, for those 35 to 39 years it was 54.3%, and for those 40 to 42 years, it was 37.7%. Overall, 497 patients were evaluable for pregnancy and 74% reported at least 1 pregnancy. At enrollment, 53% of patients reported amenorrhea and 94% resumed menses within 12 months.

At diagnosis, 36% of patients had embryo/oocyte cryopreservation, and 68 patients reported embryo transfer after enrollment on the trial. The study highlighted that a cryopreserved embryo was the only assisted reproductive technology associated with a higher chance of pregnancy (OR, 2.41; 95% CI, 1.75-4.95).

Investigators also analyzed breast cancer-free interval events, and the cumulative incidence at 3 years was 9.7% (95% CI, 6.0-15.4) for patients who received ovarian stimulation for cryopreservation at diagnosis vs 8.7% (95% CI, 6.0-12.5) for those who did not.

The second analysis aimed to investigate menstruation recovery, factors associated with time to pregnancy, and whether assisted reproductive technologies were associated with achieving pregnancy.

“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,” study author Ann H. Partridge, MD, MPH, vice chair of medical oncology, founder and director of the Program for Young Adults with Breast Cancer, director of the Adult Survivorship Program, Eric P. Winer, MD, chair in Breast Cancer Research at Dana-Farber Cancer Institute, professor of medicine at Harvard Medical School, said in a 2023 interview with CancerNetwork.

Data from the POSITIVE trial had previously been reported at the 2023 San Antonio Breast Cancer Symposium and published in The New England Journal of Medicine.^3,4 The aim of the trial was to determine if women who were scheduled to be on endocrine therapy for 5 to 10 years could take a break and still see positive results from their treatment.

Eligible patients were those who had been on endocrine therapy for 18 to 30 months and wanted to expand their families. Patients were not allowed a break from treatment of more than 2 years.

A total of 516 patients were enrolled between December 2014 to December 2019. The median follow-up was 41 months and the median time from diagnosis to enrollment was 29 months.

The median patient age at enrollment was 37 years, and 34.3% of patients were younger than 35. To be qualified for the POSITIVE trial, patients must have stopped endocrine therapy 1 month prior and have a 3-month washout period before pregnancy.

The safety threshold was 46 breast cancer events, and 44 occurred on the trial in those who took a break from treatment. The 3-year incidence rate for distant recurrence of those who received treatment interruption was 4.5% (95% CI, 2.7%-6.4%) vs 5.8% (95% CI, 4.5%-7.2%) for those who did not.

Successful pregnancies occurred in 85.7% of patients who were younger than 35 and 76.0% for those 35 to 39 years old. Assisted reproductive technology was noted in 43.3% of patients.

Competing risks in the trial included resumption of endocrine therapy, no longer attempting to become pregnant, and cancer events. The incidence of first pregnancy with competing risks occurred at 6 months from enrollment in 28.8% of patients, 53.6% at 12 months, and 70.5% at 24 months.

At the time of the database lock, 63.8% of patients had a live birth and 86.1% had at least 1 pregnancy.The most common complications of those who reported at least 1 pregnancy was hypertension or preeclampsia (3.8%), diabetes mellitus (2.4%), and placental abnormalities (1.6%). Of note, 7.9% of babies born had low birth weights, and 2.9% had birth defects.

References

1. Higher pregnancy rates and no impact on prognosis with embryo/oocyte cryopreservation at breast cancer diagnosis followed by embryo transfer after endocrine therapy interruption. News release. ESMO. June 26, 2024. Accessed June 26, 2024. https://shorturl.at/gCeFu
2. Azim HA, Niman SM, Partridge AH, et al. Fertility preservation and assisted reproduction in patients with breast cancer interrupting adjuvant endocrine therapy to attempt pregnancy. J Clin Oncol. Published May 29, 2024. doi:10.1200/JCO.23.0229
3. Partridge AH, Niman SM, Ruggeri M, et al. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388(18):1645-1656. doi:10.1056/NEJMoa2212856
4. Partridge AH, Niman SM, Ruggeri M, et al. Pregnancy outcome and safety of interrupting therapy for women with endocrine responsive breast cancer: initial results from the POSITIVE trial (IBCSG 48-14 / BIG 8-13 / Alliance A221405). Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract GS4-09.