Longitudinal Changes in Volumetric Breast Density with Tamoxifen and Aromatase Inhibitors

Abstract

Background: Reductions in breast density with tamoxifen and aromatase inhibitors may be an intermediate marker of treatment response. We compare changes in volumetric breast density among breast cancer cases using tamoxifen or aromatase inhibitors (AI) to untreated women without breast cancer.Methods: Breast cancer cases with a digital mammogram prior to diagnosis and after initiation of tamoxifen (n = 366) or AI (n = 403) and a sample of controls (n = 2170) were identified from the Mayo Clinic Mammography Practice and San Francisco Mammography Registry. Volumetric percent density (VPD) and dense breast volume (DV) were measured using Volpara (Matakina Technology) and Quantra (Hologic) software. Linear regression estimated the effect of treatment on annualized changes in density.Results: Premenopausal women using tamoxifen experienced annualized declines in VPD of 1.17% to 1.70% compared with 0.30% to 0.56% for controls and declines in DV of 7.43 to 15.13 cm³ compared with 0.28 to 0.63 cm³ in controls, for Volpara and Quantra, respectively. The greatest reductions were observed among women with ≥10% baseline density. Postmenopausal AI users had greater declines in VPD than controls (Volpara P = 0.02; Quantra P = 0.03), and reductions were greatest among women with ≥10% baseline density. Declines in VPD among postmenopausal women using tamoxifen were only statistically greater than controls when measured with Quantra.Conclusions: Automated software can detect volumetric breast density changes among women on tamoxifen and AI.Impact: If declines in volumetric density predict breast cancer outcomes, these measures may be used as interim prognostic indicators. Cancer Epidemiol Biomarkers Prev; 26(6); 930-7. ©2017 AACR.

Figure 1

Changes in Volpara and Quantra volumetric percent density (VPD) and dense breast volume (DV) with tamoxifen (TAM) therapy among premenopausal women. Panel (a): annualized changes in VPD measured by Volpara and Quantra; panel (b): annualized changes in DV measured by Volpara and Quantra; panel (c): annualized changes in Volpara VPD stratified by baseline Volpara VPD; panel (d): annualized changes in Quantra VPD stratified by baseline Quantra VPD; panel (e): annualized changes in Volpara DV stratified by baseline Volpara VPD; panel (f): annualized changes in Quantra DV stratified by baseline Quantra VPD. Circles represent estimated annualized changes in breast density; lines represent 95% confidence intervals. All analyses adjusted for age, baseline BMI, change in BMI, natural logarithm of baseline volumetric density, and study site. TAM, tamoxifen *p-value <0.05 for annualized change compared to controls

Figure 2

Changes in Volpara and Quantra volumetric percent density (VPD) and dense breast volume (DV) with tamoxifen (TAM) and aromatase inhibitor (AI) therapy among postmenopausal women. Panel (a): annualized changes in VPD measured by Volpara and Quantra; panel (b): annualized changes in DV measured by Volpara and Quantra; panel (c): annualized changes in Volpara VPD stratified by baseline Volpara VPD; panel (d): annualized changes in Quantra VPD stratified by baseline Quantra VPD; panel (e): annualized changes in Volpara DV stratified by baseline Volpara VPD; panel (f): annualized changes in Quantra DV stratified by baseline Quantra VPD. Circles represent estimated annualized changes in breast density; lines represent 95% confidence intervals. All analyses adjusted for age, baseline BMI, change in BMI, natural logarithm of baseline volumetric density, and study site. TAM, tamoxifen AI, aromatase inhibitors *p-value <0.05 for annualized change compared to controls