Abstract B46: The influence of exemestane on breast density in postmenopausal women: A cohort study nested within the NCIC CTG MAP.3 chemoprevention trial

Abstract

Abstract Background: Endogenous estradiol blood levels and high breast density are both associated with an increased risk for breast cancer (BC), but, there is conflicting evidence about whether or not they influence breast cancer risk through a shared pathway. Exemestane is an aromatase inhibitor that blocks the synthesis of estrogen and has been demonstrated to reduce the incidence of breast cancer in postmenopausal women by 65%. However the effects of exemestane on breast density remain unclear. Objectives: The primary objective of this research was to prospectively examine the relationship between exemestane versus placebo and changes in mammographic breast density (BD) in postmenopausal women during 3 or more years of treatment. Methods: The NCIC Clinical Trials Group conducted a phase III randomized controlled trial (RCT) comparing exemestane (E), with placebo (P) in postmenopausal women at higher than average risk for BC (MAP.3). This study was nested within the MAP.3 RCT using data from 568 participants across Canada and Buffalo, New York. Information on treatment allocation and established risk factors for BC was previously collected and data on the outcome measures was obtained from mammograms. Baseline and follow-up mammograms were collected from participating centres and were measured (percent density) using Cumulus software by our team radiologist (DJ). Multivariable linear regression was used to estimate the effect of exemestane treatment on >=3 year change in percent BD from randomization controlling for potential confounding variables. Results: Percent BD was measured for 386 participants (E=200, P=186) with a baseline and >=3 year follow-up mammogram that was matching in format (i.e. film or digital). The average age of women at study entry was 63 years and the average Gail score was 2.8%. The mean BD was similar in both arms at baseline (P: 12.9% (SD: 14.5) and E: 13.7% (SD: 14.4)). Similarly, the annual mean change in percent BD was not significantly different between the two treatment arms (P: 0.63% (SD: 1.82) vs E: .077% (SD: 1.80); p=0.90). After controlling for potential confounders (age, body mass index, first degree family history of BC and prior use of HRT), exemestane was not predictive of change in percent BD (p-value=0.641). Neither age (<60 vs. >=60 yrs) nor BMI modified the exemestane-breast density relationship significantly. Conclusion: We found no association between >=3 years of exemestane use and change in percent BD among a subset of postmenopausal women participating in MAP.3. These results suggest that estrogen and breast density may have independent pathways in breast cancer etiology. Citation Format: Harriet Richardson, Paul E. Goss, Melanie Walker, Doris Jabs, Will King. The influence of exemestane on breast density in postmenopausal women: A cohort study nested within the NCIC CTG MAP.3 chemoprevention trial. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B46.