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SAN ANTONIO -- Young women with early, hormone receptor (HR)-positive breast cancer attempting to become pregnant can safely pause endocrine therapy and later resume it, according to initial results from a prospective, international single-arm trial.

At a median follow-up of 41 months, the 3-year breast cancer recurrence rate for women who interrupted endocrine therapy to pursue pregnancy was 8.9%, with most women in the study going on to deliver healthy babies, reported Ann Partridge, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School in Boston.

Partridge observed that the recurrence rate was comparable to the 9.2% rate in an external control cohort from the trials, which examined adjuvant endocrine therapy in premenopausal women. The distant relapse rate of 4.5% in the current study was also comparable to that of the SOFT/TEXT cohort.

"I think this will help patients, their families, and their doctors be more comfortable, at least in the short term, to pursue a pregnancy," said Partridge during a press briefing at the San Antonio Breast Cancer Symposium.

"Interrupt -- not stop -- endocrine therapy," she emphasized. "I think that's an important part of the message, as well."

At 4 years, 8% of the cohort had either a recurrence or had died (nine deaths) before resuming endocrine therapy, 76% had resumed endocrine therapy, and 15% had not, with most in the latter group saying they were still pursuing pregnancy.

Of the 497 women followed for pregnancy status in the POSITIVE (Pregnancy Outcome and Safety of Interrupting Therapy for Women With Endocrine Responsive Breast Cancer) trial, 507 pregnancies occurred among 368 women. Of those, 86% (317 women) had at least one live birth, 19% had one miscarriage or more, and 3% had at least one abortion.

Adverse neonatal outcomes included low birth rate in 8% and birth defects in 2%, which Partridge said were not clearly associated with treatment exposures.

When asked how these rates compared with the general population, Partridge said that it is difficult to find a cohort comparable to the study population. For example, she said, the pregnancy rate in this study is much higher than that shown in population studies of women of the same age (median 37 years), simply because in the general public many women of that age are not trying to get pregnant.

However, "when you look at women going to fertility clinics and trying to become pregnant, these rates are actually a little bit lower than that rate," she added.

Study Rationale and Design

"Future fertility is of paramount importance for young breast cancer patients and survivors," said Partridge. "Many of them express the desire to have a future pregnancy at diagnosis and follow-up. However, there have been concerns that a pregnancy might increase the risk of an early-stage breast cancer coming back, particularly in the setting of a hormone receptor-positive breast cancer, where historically people have been concerned that this might be throwing fuel on the fire."

She noted that prior registry and database studies have shown that pregnancy after breast cancer does not worsen disease outcomes, regardless of hormone-receptor status, but that the standard 5 to 10 years of adjuvant endocrine therapy compromises conception because of the time it takes as women age, and the fact that the majority of women end up having chemotherapy.

POSITIVE, therefore, was designed to address whether it is safe, from a breast cancer-relapse perspective, to temporarily interrupt endocrine therapy in order to attempt pregnancy.

"The study was designed with a protocol for specific inclusion and safety criteria, because we could not do a randomized trial in this setting," she explained. "It just wouldn't be ethical, nor feasible."

Women enrolled in the study were required to have undergone 18-30 months of adjuvant endocrine therapy, with a 3-month washout period to ensure the endocrine therapy was out of their system. Women were then encouraged to try to become pregnant and get back on endocrine therapy within 24 months, and then followed over time.

The POSITIVE population included women up to the age of 42 from 116 centers in 20 countries, with 23% of the women from North America, 61% from Europe, and 16% from Asia/Pacific and Middle Eastern countries.

Overall, 75% were nulliparous, 94% had stage I/II HR-positive breast cancer, and 62% had received adjuvant chemotherapy, while the median time from breast cancer diagnosis to enrollment was 29 months.

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