Abstract P3-12-12: Serum estrogen-levels in women 48-56yrs with hormone receptor-positive breast cancer. Cross-Sectional study using an ultra-sensitive LC-MS/MS-method

Abstract

Abstract Background and Purpose: Randomized clinical trials in early stage hormone receptor positive breast cancer (HR+BC), have shown that total estrogen suppression (TES) for 5 yrs or after 2-3 yrs of tamoxifen treatment improved outcome over 5 yrs of TAM monotherapy. This relative improvement is in absolute figures most visible in patients with a high relapse risk. To achieve TES, women need to be (rendered) menopausal and treated with an oral aromatase inhibitor (AI). We measured serum estrogens in women of peri-menopausal age with HR+BC starting or on anti-hormonal agents. Methods: Serum estradiol (E2) and estrone (E1) were quantified using a sensitive liquid chromatography-tandem mass spectrometry method (LC-MS/MS; Pauwels et al. JCO 2013) in women 48-56 yrs old with HR+BC starting or on anti-hormonal therapy in a cross sectional observational monocentric study. We report the frequency that (and explore why) AI-users had estrogens above the lower limit of quantification (LLOQ). We measured estrogen levels in TAM users with > 3 months' amenorrhea by previous use of (neo)adjuvant chemotherapy. Finally, we studied the frequency of both estrogens or either alone were < LLOQ in non-users. Statistics are descriptive; biomarkers for estrogen levels were analyzed using linear mixed models. [amendment on study NCT01223833] Results: Estrogen levels were assessed in 566 samples from 401 women; 96 (126 samples) were on AI, 128 (182 samples) on TAM and 217 (258 samples) non-users. Some patients had more than one blood sample in different groups. 13,5% of AI users were above LLOQ for E2 and E1; 7,5% for E1 alone. Some were due to ovarian reactivation. An important proportion (18%) of 83 non-hysterectomized TAM users with amenorrhea had E2 levels >40ng/L; 9,1% and 28.2% respectively in patients who had and didn't have (neo)adjuvant chemotherapy. None of non-users were below LLOQ for E1, while 20.7% were below LLOQ for E2. Conclusions:TES is not always achieved in AI-users; reasons why were multiple. Amenorrhea is no guarantee for TES in TAM users, as a significant proportion had high E2 levels even when previously exposed to (neo)adjuvant chemotherapy. Using LC-MS/MS, undetectable levels for E1 better reflect TES than below LLOQ for E2. Citation Format: Van Houdt M, Neven P, Anneleen L, Ivo J, Dirk V, Jaak B, Annouschka L, Hans W. Serum estrogen-levels in women 48-56yrs with hormone receptor-positive breast cancer. Cross-Sectional study using an ultra-sensitive LC-MS/MS-method [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-12-12.