Abstract P2-09-14: Association between BMI and residual estradiol levels in post-menopausal women using adjuvant letrozole: Results of a prospective study
Authors: Cescon DW , Ennis M , Pritchard KI , Townsley C , Warr D , Elser C , Rao L , Stambolic V , Sridhar S , Goodwin PJ 
Published: March 2017

Abstract
Background: Adjuvant aromatase inhibitors (AI) are the standard of care for post-menopausal women with early breast cancer (BC). Some studies have suggested that women with high BMI have less benefit from some AIs (anastrozole, but not letrozole) vs. tamoxifen. Of concern, a positive correlation between BMI and residual estradiol in women using letrozole has been reported (ALIQUOT Study; JCO 2012). These findings have created uncertainty about the use of AIs in overweight and obese women. We conducted a prospective study to measure estrogen levels in post-menopausal women using adjuvant letrozole, with the primary objective of evaluating the relationship between residual E2 and BMI.
Methods: Post-menopausal women with early BC taking adjuvant letrozole for at least 3 months were recruited at 4 sites in Toronto, Canada. Fasting blood was collected 24 hours after the prior dose at baseline (Day 1, routine use of own letrozole, including generic) and on Day 29, following 28 days of monitored adherence to a provided supply of Femara 2.5 mg/day (Part A). Participants with BMI&gt;25 were treated for a further 28 days (Part B) with a double dose of Femara (5 mg/day). Estradiol and estrone were measured using a high sensitivity liquid chromatography-tandem mass spectrometry assay. Vitamin D and markers of obesity/inflammation were assayed, and symptom/quality of life questionnaires completed at the same time points.
Results: 112 eligible patients were enrolled and completed Part A. Median age was 62 and BMI 24.7 kg/m2 (range 19.0 to 42.2 kg/m2). 68% of participants had received adjuvant chemotherapy. Estradiol levels (mean±SD) were 2.81±1.15 pg/mL at baseline (typical use) and 2.69±1.01 pg/mL at Day 29 following monitored Femara use with near-perfect adherence (p=NS). No significant correlation was observed between estradiol and BMI on either Day 1 or Day 29 (r=0.06, p=NS). As previously reported, letrozole 5 mg/day dose did not affect residual estradiol levels at Day 58 for women with BMI&gt;25. Residual estradiol was not correlated with vitamin D or markers of obesity/inflammation (insulin, leptin, CRP).
Conclusion: No association was observed between BMI and residual estradiol in women using letrozole (generic or Femara) at standard doses. These results are consistent with the absence of a treatment-by-BMI interaction in the BIG 1-98 trial and they provide reassurance that letrozole is an appropriate treatment in overweight and obese women.
Funded by Hold 'Em For Life (Mount Sinai Hospital, Toronto) and Breast Cancer Research Foundation.
Citation Format: Cescon DW, Ennis M, Pritchard KI, Townsley C, Warr D, Elser C, Rao L, Stambolic V, Sridhar S, Goodwin PJ. Association between BMI and residual estradiol levels in post-menopausal women using adjuvant letrozole: Results of a prospective study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-09-14.