Can breast cancer survivors temporarily stop endocrine therapy to attempt pregnancy?

Young breast cancer survivors could safely temporarily stop adjuvant endocrine therapy (ET) to attempt pregnancy, according to primary results of the POSITIVE* trial presented at SABCS 2022.

Participants in this international (116 centres in 20 countries), single-arm trial were 518 stage I–III hormone receptor (HR)+ breast cancer survivors aged ≤42 years (median age 37 years) who had been on adjuvant ET for 18–30 months and who desired pregnancy. They were enrolled in the trial within 1 month of stopping ET, had a 3-month washout period, followed by a ≤2-year break from ET to allow for conception, delivery, and/or breastfeeding, before resuming ET.

Seventy-five percent of the participants were nulliparous. The median time between breast cancer diagnosis and trial enrolment was 29 months, 94 percent were diagnosed with stage I–II disease, 66 percent had node-negative disease, and 62 percent had received neoadjuvant or adjuvant chemotherapy. The most common ET regimens used were tamoxifen only (41.7 percent) and tamoxifen + ovarian suppression (35.7 percent).

The participants were followed up for a median 41 months, during which time 44 participants experienced a breast cancer-free interval (BCFI) event (time from enrolment to first local, regional, or distant recurrence, or a new invasive contralateral breast cancer event). [SABCS 2022, abstract GS4-09]

This number did not exceed the pre-specified safety threshold of 46 events. The 3-year BCFI failure rate was 8.9 percent, which was similar to the 9.2 percent rate observed in an external control group comprising premenopausal women on adjuvant ET enrolled in the SOFT/TEXT trials, said the authors.

A total of 497 participants were followed for pregnancy status. Seventy-four percent of the participants (n=368) had ≥1 pregnancy, with 70 percent becoming pregnant within 2 years. Of the participants who became pregnant, 86 percent (n=317) had ≥1 live birth (64 percent of all enrolled).

Nineteen percent of the participants experienced ≥1 miscarriage and 3 percent had ≥1 abortion.

The incidence of low birth weight and presence of birth defects was low, documented in 8 and 2 percent, respectively.

At 48 months, 8.3 percent experienced cancer recurrence or death (nine deaths) prior to restarting ET. Seventy-six and 15 percent had and had not resumed ET, respectively.  

“Forty to 60 percent of patients who are diagnosed with breast cancer at age ≤40 are concerned about their future fertility, especially if the disease occurs before they could decide whether to become a mother or not,” said study lead author Professor Ann Partridge from the Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, US.

Professor Ann Partridge (© MedMeetingImages/Scott Morgan 2022)

“Especially for women with HR+ breast cancer, where there’s been historical concern that having a pregnancy might be akin to pouring gasoline on the flames, we’ve worried that that may increase the risk of breast cancer recurrence and poor outcomes,” she highlighted. [https://ascopost.com/videos/2022-san-antonio-breast-cancer-symposium/ann-partridge-on-interrupting-breast-cancer-treatment-to-attempt-pregnancy/, accessed 14 December 2022]

“[In addition,] standard 5–10 years of adjuvant ET compromises conception in women with HR+ disease,” she continued.

“The POSITIVE trial provides important data to support young women with HR+ early breast cancer who are interested in a pregnancy and taking a break from ET to pursue one,” said Partridge. “These data [also] stress the need to incorporate patient-centred reproductive healthcare in the treatment and follow-up of young women with breast cancer.”

The short follow-up period was a limitation, the authors said. “We want to follow these women for at least 10 years so that we can know that it’s not only safe in the first few years but [also] in the long term. That’s going to be critical particularly in the setting of HR+ breast cancer where we know there is the risk of late recurrence,” Partridge concluded.