Young women with early-stage breast cancer who wish to get pregnant can suspend and then return to endocrine therapy with the same rate of disease recurrence as those who did not pause therapy to conceive, according to results from an international trial presented during the San Antonio Breast Cancer Symposium (SABCS) held December 6-10, 2022 (Abstract GS4-09). Researchers said the results should alleviate long-standing concerns that disruption of endocrine therapy to pursue pregnancy may increase the risk of early-stage breast cancer returning, particularly among young women with hormone receptor-positive (HR+) breast cancer.
"I think women will feel more comfortable trying to pursue a pregnancy in this setting with these fairly reassuring data," said Ann Partridge, MD, MPH, Vice Chair of Medical Oncology with Dana-Farber Cancer Institute in Boston and Professor of Medicine at Harvard, who presented the study's findings. Even more reassuring, Partridge and colleagues said most of these women went on to have successful pregnancies and healthy babies.
"I think this is great news," said Carlos Arteaga, MD, the Lisa K. Simmons Distinguished Chair of Comprehensive Oncology at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center in San Antonio. "As Dr. Partridge indicated, maybe longer follow-up is indicated, but so far, the data would suggest that the risk of recurrence is not any higher for these women who chose to interrupt their therapy to get pregnant and then resuming." Arteaga did not participate in this study.
According to recent American Cancer Society statistics, an estimated 12,080 women younger than 40 in the U.S. were diagnosed with breast cancer in 2022, or about 5 percent of new breast cancers. Many of these young women with early disease are prescribed endocrine therapy such as ovarian function suppression, aromatase inhibitors, or selective estrogen modulators. Many also remain concerned that breast cancer treatment will make it difficult to conceive or that pregnancy might worsen their cancer. Only about 5-10 percent of these patients go on to become pregnant.
That said, Olivia Pagani, MD, the International Study Chair on behalf of the International Breast Cancer Study Group and the trial's co-author, noted that retrospective studies have shown that pregnancy after cancer is feasible and safe.
The POSITIVE (Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer) trial is the first international prospective single-arm trial that seeks to resolve this common concern among young women facing this question: Is it safe from a breast cancer relapse perspective to temporarily interrupt endocrine therapy to attempt pregnancy?
From December 2014 to December 2016, some 516 patients with a median age of 37 years were enrolled in the trial from across 116 centers in 20 countries on four continents. About 94 percent of the patients had Stage I or II breast cancer, with 63 percent having received adjuvant chemotherapy. The median time of breast cancer diagnosis among the cohort was 29 months. Prior to enrollment, patients were required to undergo endocrine therapy for 18-30 months. This regimen was followed by a 3-month "washout" to make sure all signs of the endocrine therapies were eliminated from a woman's system.
During the trial, three safety analyses were conducted by a monitoring committee, since it was impossible, both ethically and feasibly, to conduct a randomized trial in this setting, Partridge said during a press briefing. If more than 46 breast cancer recurrences occurred within some 3 years of average follow-up, the trial would have been discontinued. That mark was never reached.
At the study's median follow-up of 41 months, some 44 participants in the trial experienced a recurrence of their cancer (8.9%). This compared favorably to 9.2 percent in a control group of patients from the SOFT/TEXT trial, which analyzed adjuvant endocrine therapy in premenopausal women. At 48 months, about 8 percent of the cohort experienced cancer recurrence before resuming endocrine therapy, with a total of nine patients dying before returning to endocrine therapy, or about 1.5 percent of the patient population.
Of note, some 79 percent of women who were disease-free had not yet resumed endocrine therapy at the 2-year mark. Most of these women were either continuing their pursuit of pregnancy, were recently or actively pregnant, or were breastfeeding.
Asked during a press briefing if the researchers would consider extending the trial limit beyond 2 years, Partridge said: "The actual time it took for the people to get back on endocrine therapy, the median, was actually over 2 years. And so many women did not become pregnant within the first 2 years, but they did subsequently, which is in part why we're seeing some of the delay getting back onto endocrine therapy. So, de facto, they did delay it."
As for pregnancy outcomes, about 74 percent (368) of 487 women followed for pregnancy status had at least one pregnancy, for a total of 507 pregnancies resulting in at least 317 live births, or about 64 percent of all enrolled patients. The pregnancy rates for this cohort of women with a median age of 37 years was higher than the general population, since women of that age generally are not trying to get pregnant, Partridge said.
About 19 percent experienced at least one miscarriage, with about 3 percent undergoing a therapeutic abortion. Some 8 percent of babies were delivered at a low birth weight. The incidence of birth defects was low, about 2 percent, with none linked to treatment exposure.
Long-term follow-up both to monitor endocrine therapy resumption and long-term disease outcomes, particularly among women with HR+ disease, are ongoing, Partridge said. She noted that short-term follow-up to data is a limitation of the POSITIVE study, as HR+ breast cancer can recur many years after initial diagnosis.
"I think these (findings) will help patients, their families, and their doctors to feel comfortable at least in the short term with these data to pursue pregnancy and interrupt, not stop, endocrine therapy. I think that's an important part of the message as well," Partridge noted.
Warren Froelich is a contributing writer.