Abstract PO5-02-01: Concerning Discrepancies in Estradiol Levels in Premenopausal Women Receiving Abemaciclib and Ovarian Function Suppression
Authors: Kessler Alaina , Patel Rima , Gallagher Emily , Sheng Tianxiang , Mendu Damodara Rao , Tiersten Amy , Klein Paula , Bhardwaj Aarti , Goel Anupama , Sparano Joseph , Shao Theresa , Fasano Julie 
Published: May 2024

Abstract
Background: Adjuvant abemaciclib in combination with endocrine therapy improves outcomes for patients with high-risk, hormone receptor-positive (HR+), HER2-negative early-stage breast cancer. In premenopausal women, the use of an aromatase inhibitor (AI) requires chemical or surgical ovarian function suppression (OFS). Our published case report of a premenopausal woman receiving adjuvant abemaciclib with elevated estradiol levels measured by the Abbott Alinity chemiluminescent microparticle immunoassay (CMIA) despite bilateral salpingo-oophorectomy (BSO) but low estradiol levels using liquid chromatography-mass spectrometry (LC-MS/MS) suggested an interference of abemaciclib with the immunoassay (PMID: 37124155). The aim of this study was to determine discrepancies in estradiol levels using CMIA compared to LC-MS/MS and subsequent treatment changes in a larger patient population.
Methods: We conducted an IRB-approved retrospective review of premenopausal women with early-stage HR+ breast cancer treated with adjuvant OFS and abemaciclib at our institution from October 2021 to April 2023 who had at least 1 CMIA estradiol level drawn during abemaciclib therapy. Pathology, treatment plans, and lab data were abstracted from medical records. Postmenopausal estradiol levels were based on reference ranges of &lt; 41 pg/mL using CMIA or &lt; 15 pg/mL using LC-MS/MS. We utilized descriptive statistics to describe the population and management.
Results: We identified 22 patients who met criteria for our review. The average age was 42.3 years, all had positive axillary nodes, 6 (27%) received neoadjuvant chemotherapy, and 15 (68%) received adjuvant chemotherapy. There were 14 (64%) patients who received leuprolide and 8 (36%) received goserelin, whereas 19 (86%) received AI and 3 (14%) received tamoxifen as their initial oral antiestrogen therapy. The majority of patients did not have baseline estradiol levels when starting OFS though after starting abemaciclib, 20 patients had CMIA estradiol levels in the premenopausal range, 9 of which had estradiol monitored by both CMIA and LC-MS/MS (Table 1). The average length of time from starting OFS to starting abemaciclib was 144.6 days with 1 patient switching from tamoxifen to OFS and AI after starting abemaciclib. Due to elevated CMIA estradiol, treatment changes included increased OFS dosage (5 patients), change of OFS (2 patients), and change to tamoxifen (3 patients). There were 6 patients who underwent BSO, 3 due to persistently elevated CMIA estradiol levels, 2 due to patient preference, and 1 due to a BRCA mutation. Following surgery, 2 patients had persistently elevated CMIA estradiol but low LC-MS/MS estradiol. The remainder of these patients did not have estradiol levels measured by CMIA.
Conclusions: Our retrospective review demonstrated the likely interference of abemaciclib with the Abbott Alinity immunoassay as shown by 9 patients treated with OFS and abemaciclib with simultaneous premenopausal range CMIA estradiol levels and postmenopausal range LC-MS/MS estradiol levels. As up to 91% of patients in our study may have had a false positive estradiol level erroneously suggesting inadequate OFS, monitoring of estradiol levels using the CMIA assay in patients receiving adjuvant abemaciclib in addition to OFS could lead to changes in therapy that may be unnecessary. It is recommended that the LC-MS/MS assay be used when monitoring of estradiol levels is indicated in patients receiving abemaciclib concurrently with OFS.
Table 1: Estradiol levels in patients receiving OFS and abemaciclib who had both CMIA and LC-MS/MS assays
Citation Format: Alaina Kessler, Rima Patel, Emily Gallagher, Tianxiang Sheng, Damodara Rao Mendu, Amy Tiersten, Paula Klein, Aarti Bhardwaj, Anupama Goel, Joseph Sparano, Theresa Shao, Julie Fasano. Concerning Discrepancies in Estradiol Levels in Premenopausal Women Receiving Abemaciclib and Ovarian Function Suppression [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-01.