Abstract P5-12-11: Measuring ovarian escape in pre-menopausal breast cancer patients on ovarian suppression therapy

Abstract

Abstract Introduction The results of the SOFT and TEXT trials created a paradigm shift in the management of pre-menopausal women with estrogen (ER) or progesterone (PR) receptor positive breast cancer. With findings demonstrating reduced recurrence in high risk patients, the American Society of Clinical Oncology (ASCO) recommended that many in this patient population should receive ovarian suppression (OS) with adjuvant endocrine therapy. However, ancillary analysis of the SOFT trial noted a population of patients with persistently elevated estradiol levels. The clinical significance of this is unknown. The aim of this study was to assess pre-menopausal patients with ER positive breast cancer, in a “real world” clinical setting, who did not achieve maximal estradiol suppression within 3 months, and to evaluate potential contributing risk factors. Methods/Materials This was a single institutional, retrospective, observational study, from February 1, 2010 to January 9, 2018, that evaluated pre-menopausal women receiving adjuvant endocrine therapy with OS (either leuprolide or goserelin). Patients were included if they were receiving adjuvant ovarian suppression with goserelin or leuprolide, had stage I-III ER or PR positive breast cancer, and had at least one estradiol value checked within the first 3 months. The primary objective was to measure the percentage of women with ovarian escape, defined as estradiol level >2.7 pg/mL within 3 months of initiation of OS therapy if on AI therapy, and >21 pg/mL for those patients on tamoxifen. The secondary aim was to associate baseline clinical data (age, body mass index (BMI), and previous receipt of chemotherapy) with higher probability of ovarian escape. Results Between February 1, 2010 and January 9, 2018, 46 patients met inclusion criteria. There were 20 (43.5%) women on tamoxifen and 26 (56.5%) women on an aromatase inhibitor. In the first 3 months, 12 (26.0%) patients failed to achieve maximal OS. Eleven of these continued on OS therapy and 4 (36.3%) did not achieve OS at 6 months. Of these 4 patients who did not achieve ovarian suppression by 6 months, 3 women continued for a total of 12 months, and none of them achieved OS, yielding 6.5% of the total 46 patients who did not achieve ovarian suppression within 1 year. Age was significantly associated with risk of ovarian escape, with older patients (43.0±6.6 years) much more likely to achieve OS within 3 months, compared to younger women (38.5±6.7) (p = 0.037). This difference remained significant in multi-variate analysis. In contrast, BMI, previous chemotherapy, and drug used (leuprolide vs. goserelin) were not significantly associated with likelihood of achieving ovarian suppression. Conclusion It is not uncommon for premenopausal women to have elevated estradiol levels within the first 3 months of ovarian suppression therapy. In this “real world” clinical setting, approximately 1 in 4 women were not maximally suppressed within 3 months. Of these women who did not achieve ovarian suppression in the first 3 months, a quarter of them were also not able to achieve ovarian suppression in the first year. Young age was the most significant risk factor for ovarian escape. Given the relatively high frequency of this phenomenon, larger future studies should evaluate whether ovarian escape in young, pre-menopausal women may be associated with higher recurrence risk, and thus warrant closer monitoring of hormone levels. Table 1: Baseline characteristics by ovarian suppressionAchieved ovarian suppression within 3 monthsp-valueNo (n=11)Yes (n=35)Age38.5±6.743.0±6.60.037BMI29.0±7.627.5±6.50.677Previous Chemotherapy6 (54.6%)21 (60%)1.0Drug0.768Anastrozole3 (27.3%)11 (31.4)Exemestane0 (0%)4 (11.4)Letrozole3 (27.3%)5 (14.3)Tamoxifen5 (45.5%)15 (42.3) Citation Format: Ethan Burns, Susan Xu, Edward McLean, Rosetta Lee, Tejal Patel, Jenny Chang, Polly Niravath. Measuring ovarian escape in pre-menopausal breast cancer patients on ovarian suppression therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-11.