Premenopausal Women with Early Breast Cancer Treated By Oestradiol Suppression Have Severely Deteriorated Bone Microstructure

Presentation Number: LB SUN 44
Date of Presentation: April 2nd, 2017

Sabashini K Ramchand*1, Ego Seeman1, Xiao-Fang Wang1, Ali Ghasem-Zadeh1, Prudence A Francis2, Evangeline J Ponnusamy2, Michele S Bardin3, Minh Bui4, Roger M Zebaze1, Jeffrey D Zajac1 and Mathis Grossmann1
1The University of Melbourne, Australia, 2Peter MacCallum Cancer Centre, Melbourne, Australia, 3Austin Health, Melbourne, Australia, 4University of Melbourne, Australia

Abstract

Background In premenopausal women with early oestrogen-receptor-positive breast cancer, combined ovarian suppression and aromatase inhibition result in a precipitous decline in oestradiol production. The resulting unbalanced and rapid bone remodelling replaces older more mineralised bone with a smaller volume of less fully mineralised new bone. We hypothesised that these changes result in severe trabecular and cortical microstructural deterioration and reduced matrix mineralisation density.

Methods We conducted a cross-sectional study involving 27 premenopausal women, mean age 43·3 years (range 30·4 to 53·7) with early breast cancer (‘cases’) made oestradiol deficient for 17 months (range 6-120) by combined ovarian suppression and aromatase inhibition, 42 healthy age-matched premenopausal controls and 35 healthy postmenopausal controls, mean age 62·6 years (range 60·2 to 65·5). Images of the distal radius and distal tibia were acquired using high-resolution peripheral quantitative computed tomography. Cortical and trabecular microstructure were quantified using the StrAx1·0 algorithm.

Findings Compared with premenopausal controls, cases had 0·75 SD (95% CI 0·21 to 1·29) lower distal radial trabecular bone volume fraction (bone volume/tissue volume, BV/TV) due to 1·29 SD (0·71 to 1·87) fewer trabeculae. Cortical porosity was 1·25 SD (0·59 to 1·91) higher. Compared with postmenopausal controls 20 years older, cases had comparable or lower trabecular BV/TV and comparable cortical porosity. Matrix mineral density was 1·56 SD (0·90 to 2·22) lower in cases than in premenopausal controls and 2·17 SD (1·50 to 2·84) lower than in postmenopausal controls. Results at the tibia were similar.

Interpretation The longevity of premenopausal women with early breast cancer treated with endocrine therapy and the severe microstructural deterioration associated with oestradiol depletion provide a compelling rationale to investigate the efficacy of antiresorptive therapy.

 

Disclosure: ES: research support and lectured at national and international meeting symposia funded by Amgen, Amgen, research support and lectured at national and international meeting symposia funded by Allergan, Allergan, research support and lectured at national and international meeting symposia funded by Asahi, Asahi, research support and lectured at national and international meeting symposia funded by Genzyme, Genzyme Corporation, research support and lectured at national and international meeting symposia funded by Merck and Co., Merck & Co., Director of the board and shareholder in StraxCorp, renumerated by StraxCorp as chief medical officer and is one of the inventors of StrAx 1.0 algorithm. No financial compensation was derived from the submitted work. , StraxCorp.. PAF: Speaker, Astra Zeneca. RMZ: Researcher, Amgen, Researcher, Merck & Co., Researcher, Servier, Researcher, Warner Chilcott, Researcher, AKP, Researcher, Genzyme Corporation, Researcher, Sanofi, Board Member, StraxCorp, Australia. Nothing to Disclose: SKR, XFW, AG, EJP, MSB, MB, JDZ, MG