POSITIVE trial knowledge introduced at this 12 months’s San Antonio Breast Cancer Symposium present that amongst girls with hormone receptor–constructive (HR+) breast most cancers who paused adjuvant endocrine remedy (ET) to aim being pregnant, 94% who reported amenorrhea at enrollment resumed their durations inside 6 months. In addition, embryo switch after embryo/oocyte cryopreservation at prognosis had increased charges of being pregnant vs ovarian tissue cryopreservation and gonadotropin hormone-releasing hormone (GnRH) agonists for ovarian stimulation.

Hatem Azim, Jr, Md, PhD

Image Credit: Tecnológico de Monterrey

Lead investigator Hatem Azim, Jr, Md, PhD, adjunct professor of oncology, School of Medicine, Tecnológico de Monterrey, Mexico, introduced the up to date outcomes on this 12 months’s session, “Fertility Preservation and Assisted Reproductive Technologies (ART) in Breast Cancer (BC) Patients (Pts) Interrupting Endocrine Therapy (ET) to Attempt Pregnancy.”

“Many breast cancer patients may opt for fertility preservation prior to starting cancer treatment and/or may use assisted reproductive technologies to increase their chances of pregnancy,” mentioned Hazim in a press release saying the outcomes.¹ “Yet, there is 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+ breast cancers.”

Data on these secondary outcomes of menstruation and use of assisted reproductive expertise (ART) replace POSITIVE trial (NCT02308085) major consequence knowledge on breast most cancers–free interval introduced eventually 12 months’s assembly, which confirmed an analogous small price of illness recurrence among the many research inhabitants vs exterior controls from the SOFT (NCT00066690) and TEXT (NCT00066703) trials after 41 months of follow-up: 8.9% vs 9.2%.^2,3 At that point, second creator Ann Partridge, MD, MPH, vice chair of medical oncology at Dana-Farber Cancer Institute and professor of drugs at Harvard Medical School, famous, “Results to date indicate that the decision to pause therapy can be made safely, in consultation between women and their physicians.”²

POSITIVE enrolled premenopausal girls inside 1 month of stopping ET who had stage 1-3 HR+ breast most cancers, all of whom have been 42 years and youthful at enrollment, had 18 to 30 months of adjuvant ET, and didn’t have scientific proof of recurrence. Additional secondary outcomes are being pregnant outcomes, offspring outcomes, breastfeeding, adherence to ET, and distant recurrence-free intervals. All sufferers have been requested to maintain a 2-year menstrual diary, and using any ART was allowed. After a 3-month washout interval, there was a most 2-year break to permit for conception, supply, and breastfeeding. This was adopted by resuming ET for five or 10 years.

Data for this secondary evaluation once more have been collected after a median 41 months of follow-up. Of the 518 total research inhabitants, 516 have been included within the menstruation evaluation and 497 within the fertility preservation and ART evaluation.

Statistics between the teams have been comparable: 66% every have been 35 years or older, 34% every have been lymph node-positive, 62% every reported prior chemotherapy, and 75% every reported no prior reside start.

During the course of the research, 94% of the 273 sufferers who reported amenorrhea at enrollment—53% of the secondary evaluation inhabitants—had restarted their durations. At the 6-month mark, breaking this down by adjuvant remedy, 90% who didn’t obtain adjuvant ET had resumed their durations vs 85% who had obtained chemotherapy plus GnRH analogs and 81% who had obtained chemotherapy however not GnRH analogs.

Seventy-four % reported a minimum of 1 being pregnant, and a shorter time to being pregnant was seen among the many girls youthful than 35 years. At 12 months since research enrollment, 64% reported a minimum of 1 being pregnant vs 38% of these aged 40 to 42 years. This hole widened to 80% and 50% by 24 months since research enrollment. The ultimate age group on this evaluation, girls aged 35 to 39, had a being pregnant price that fell in between.

In a multivariate mannequin that included prior start, irregular vs persistent amenorrhea, no ET vs chemotherapy alone, and remedy with selective estrogen receptor modulator (SERM) plus ovarian operate suppression vs SERM solely, “only younger age was associated with a short time to pregnancy,” Azim famous. Compared with girls aged 35 to 39 and 40 to 42 years, girls 35 years and youthful had 26% and 60% better possibilities of changing into pregnant.

Among the ladies reporting fertility preservation at breast most cancers prognosis or who underwent ART after POSITIVE enrollment, ovarian stimulation for embryo/oocyte cryopreservation (36%), ovarian stimulation for IVF (16%), and cryopreserved embryo switch (14%) have been the highest 3 strategies used. Overall, 51% of the secondary evaluation inhabitants underwent fertility preservation at prognosis and 43% underwent ART.

When taking a look at affected person traits by alternative of ART, girls who underwent embryo or oocyte cryopreservation reported the very best charges of prior adjuvant chemotherapy (71%). The girls who underwent switch of cryopreserved embryos have been extra more likely to be 35 years or older (76%), be lymph node-positive (44%), and report prior adjuvant chemotherapy (71%). Those who underwent ovarian stimulation for IVF have been extra more likely to be older (71%). Just over 85% total have been nulliparous.

In addition, cryopreserved embryo switch was the one modality considerably related to the next probability of being pregnant, with girls who underwent the process having a 2.41 better odds of being pregnant vs those that underwent a special ART process (1.8 increased odds) or no ART (1.41 increased odds), with no impact on their breast most cancers prognosis. Independent of using ART, youthful age (youthful than 35 vs 35-39 and 40-42 years) was related to 50% and 84% better possibilities of being pregnant, respectively.

Lastly, when taking a look at ovarian stimulation and breast most cancers outcomes, “We did not find any meaningful difference between patients who underwent ovarian stimulation and those who did not,” Azim mentioned. There have been equal charges in BCFI cumulative incidence after 3 years. After prognosis in those that did this as a part of their embryo/oocyte cryopreservation vs those that didn’t, the BCFI charges have been 9.7% and eight.7%, respectively. For those that did ovarian stimulation for IVF as a part of ART vs those that didn’t, at 2 years, there have been 2 and eight BC occasions, respectively.

“Obviously, that is the biggest potential research to research fertility preservation and assisted reproductive expertise in sufferers with early HR+ breast most cancers who need future being pregnant, underscoring the significance of oncofertility counseling in younger sufferers with breast most cancers,” Azim mentioned in a press conference saying these outcomes.

Previous research showed safety for pregnancy after breast cancer, regardless of HR status and that adjuvant ET can have an adverse impact on future fertility, but that uncertainty remains for pregnancy outcomes among those with HR+ disease undergoing ovarian stimulation.^4-6

The estimated primary completion date for POSITIVE is December 2025, and the estimated study completion date is December 2028.⁷

References

1. Patients with HR-positive breast cancer may use fertility preservation and assisted reproductive technologies without increased risk of recurrence. News release. American Association for Cancer Research. December 7, 2023. Accessed December 8, 2023. https://aacr.ent.box.com/s/iim2ep4gyeux1k985golspb3qotpk691
2. Pausing breast most cancers remedy to get pregnant, and different information from SABCS 2022. American Association for Cancer Research. January 12, 2023. Accessed December 8, 2023. https://www.aacr.org/blog/2023/01/12/pausing-breast-cancer-treatment-to-get-pregnant-and-other-news-from-sabcs-2022/
3. Highlights from SABCS 2022 scientific trial knowledge. Pharmacy Times®. January 16, 2023. Accessed December 8, 2023. https://www.pharmacytimes.com/view/highlights-from-sabcs-2022-clinical-trial-data
4. Azim HA, Kroman N, Paesmans M, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol. 2013;31(1):73-79. doi:10.1200/JCO.2012.44.228
5. Turan V, Lambertini M, Lee D-Y, et al. Association of germline BRCA pathogenic variants with diminished ovarian reserve: a meta-analysis of individual patient-level data. J Clin Oncol. 2021;39(18):2016-2024. doi:10.1200/JCO.20.02880
6. 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
7. Pregnancy consequence and security of interrupting remedy for ladies with endocrine responsive breast most cancers (POSITIVE). Clinicaltrials.gov. Updated March 16, 2023. Accessed December 8, 2023. https://clinicaltrials.gov/study/NCT02308085