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 VolparaTM (Matakina Technology) and QuantraTM (Hologic) software. Linear regression estimated the effect of treatment on annualized changes in density. Results: Premenopausal women using tamoxifen experienced annualized declines in volumetric percent density of 1.17% to 1.70% compared with 0.30% to 0.56% for controls and declines in dense breast volume of 7.43 cm3 to 15.13 cm3 compared with 0.28 cm3 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 volumetric percent density than controls (Volpara p=0.02; Quantra p=0.03), and reductions were greatest among women with ≥10% baseline density. Declines in volumetric percent density 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.
- Received November 7, 2016.
- Revision received January 5, 2017.
- Accepted January 6, 2017.
- Copyright ©2017, American Association for Cancer Research.