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Fertility Preservation Does Not Increase Risk of Recurrence of HR–Positive Breast Cancer

January 2024, Vol 14, No 1

San Antonio—Using fertility preservation and/or assisted reproductive technologies (ART) did not adversely impact 3-year cancer recurrence rates among patients with hormone receptor (HR)–positive breast cancer who paused endocrine therapy to become pregnant.

In the latest results from the POSITIVE study, which included 497 participants evaluable for the fertility preservation and ART analysis, pausing endocrine therapy for <2 years to attempt pregnancy did not increase patients’ risk of breast cancer recurrence for ≥3 years. In addition, 368 (74%) of the 497 became pregnant, said Hatem A. Azim Jr, MD, PhD, adjunct professor, School of Medicine and Breast Cancer Center at the Tecnológico de Monterrey, Mexico, at the 2023 San Antonio Breast Cancer Symposium (SABCS).

Among the patients who underwent fertility preservation, 179 used embryo or oocyte cryopreservation prior to enrollment in the POSITIVE trial, whereas 215 used ART to attempt pregnancy after enrollment. The most commonly used ART was ovarian stimulation for in vitro fertilization and cryopreserved embryo transfer.

The study “underscores the importance of early fertility counseling for young breast cancer patients,” said Dr Azim. “This is the largest prospective study to investigate fertility preservation and ART in patients with hormone receptor [HR]–positive breast cancer who desired pregnancy,” he said. “We believe that these data are of paramount importance for the oncofertility counseling of young breast cancer patients.”

At last year’s SABCS, data from the primary analysis of POSITIVE were presented, showing that temporary interruption of endocrine therapy to allow pregnancy does not increase the risk of recurrence at a median follow-up of 41 months. However, with the increasing age of childbearing, “it is becoming more likely that women will be diagnosed with breast cancer before starting or completing their families,” he said. “Many breast cancer patients may opt for fertility preservation prior to starting cancer treatment and/or may use ART to increase their chances of pregnancy. [However] there is a concern within the medical community that the use of fertility preservation or ART methods, particularly those that entail the use of hormones, could have detrimental effects on patients with HR–positive breast cancers.”

Some 51% underwent fertility preservation at breast cancer diagnosis: 179 (36%) underwent ovarian stimulation for embryo/oocyte cryopreservation, 67 (13%) took gonadotropin-releasing hormone agonists during chemotherapy, and 30 (6%) underwent ovarian tissue cryopreservation.

A key finding was that that ovarian stimulation for cryopreservation was not associated with worse disease outcomes.

Of 516 participants eligible for the menstruation analysis, 66% were ≥35 years old. Approximately half (53%) reported no menstruation at enrollment, an expected finding considering that many of the women were treated with ovarian suppression as a part of their adjuvant endocrine therapy.

“What was quite encouraging was that almost all women resumed menses on the study,” he said. Of these, 85% resumed menses at 6 months and 94% resumed menses at 12 months.

A key finding was that that ovarian stimulation for cryopreservation was not associated with worse disease outcomes, with 9.7% of patients who underwent this procedure experiencing a breast cancer recurrence within 3 years compared with 8.7% of those who did not undergo the procedure.

Of the 179 patients who had undergone ovarian stimulation for embryo/oocyte cryopreservation at diagnosis and prior to enrollment, 37.9% reported cryopreserved embryo transfer after enrollment. Of the 215 patients who used any form of ART after enrollment into POSITIVE, 37.2% underwent ovarian stimulation for in vitro fertilization (FIVET) or intracytoplasmic sperm injection (ICSI). The pregnancy rates were 82.4% and 67.5% for women who underwent cryopreserved embryo transfer and FIVET/ICSI, respectively.

The cumulative incidence of pregnancy at 12 months was 64%, 54%, and 38% for patients ages <35 years, 35 to 39 years, and 40 to 42 years, respectively.

“We found a clear association between young age at enrollment and shorter time to pregnancy,” said Dr Azim. “At 2 years, 80% of the women <35 years old at enrollment had ≥1 pregnancy, compared with 50% of women aged 40 to 42.” In a multivariable model, age was the only factors that significantly affected time to pregnancy.

Cryopreserved embryo transfer more than doubled the chance of pregnancy compared with no ART (odds ratio, 2.41; 95% confidence interval, 1.17-4.95), and women <35 years old had a 50% greater chance of having a pregnancy compared with women aged 35 to 39 years and an 84% greater chance than women 40 to 42 years old, independent of the use of ART.

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