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. Materials and 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 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.

Effect of Bazedoxifene and Conjugated Estrogen (Duavee) on Breast Cancer Risk Biomarkers in High-Risk Women: A Pilot Study

“…Small changes in density in the SMART trials might have been missed with the Cumulus semiautomated method if baseline density is low, as is often the case in postmenopausal women (25). Change in FGV volume after 6 months of Duavee (median total for both breasts of À12 cm 3 or À6 cm 3 /per breast) in our pilot is in the range of the annual change in FGV of À8 cm 3 over an average of 3 years in contralateral breasts for premenopausal women with breast cancer taking tamoxifen (42). In addition to breast cancer risk, endogenous levels of progesterone in postmenopausal women have been reported as positively correlated with percent mammographically dense area (43).…”

Breast density: why all the fuss?

“…At least one small study has correlated the likelihood of breast cancer recurrence after adjuvant tamoxifen with reductions in MRI FGV, finding that PMD reduction on tamoxifen was the only independent factor associated with recurrence; mean reduction was around 20% in the group without recurrence and only 2-6% in the group with recurrence (235). in dense volume and VBD in cases compared to controls using Volpara and Quantra; reductions were greatest when baseline VBD was more than 10% (236). Concerning other SERMs such as raloxifene, and AIs, the data for the use of MD as a biomarker is less robust and reported reductions in MD appear to be less and very heterogeneous.…”

Can Dietary and Physical Activity Modifications Reduce Breast Density in Postmenopausal Women? The DAMA Study, a Randomized Intervention Trial in Italy

“…These measures were obtained on different scales and therefore comparisons are difficult. A recent observational study in breast cancer patients showed an association between endocrine therapies and reduction on digitally obtained volumetric breast density (53) but no data are available so far, on the magnitude of the effect with a prognostic significance.…”