Abstract P6-10-09: Effect of chemoprevention uptake on mammographic density over time in women at high risk for breast cancer
Authors: Namburi S , Coe AM , Thomas P , Hershman D , Sandoval R , Maria A , Crew KD 
Published: May 2016

Abstract
Background:
Mammographic density (MD) is an independent risk factor for breast cancer, but whether chemoprevention can modify this risk biomarker is unknown. MD naturally declines with age, particularly after menopause. Prior studies have shown a significant decrease in MD with tamoxifen correlated with decreased breast cancer incidence, however, other anti-estrogens, such as aromatase inhibitors (AIs) and raloxifene, have not shown significant effect. No studies have examined the long-term effects (&gt;24 months) of chemoprevention on MD.
Methods:
We conducted a retrospective cohort study of high-risk women seen at an academic breast center. Patients were considered to be at high risk for breast cancer and eligible for chemoprevention if they had a 5-year predicted breast cancer risk according to the Gail model of ≥1.67%, atypical ductal or lobular hyperplasia, history of ductal or lobular carcinoma in situ, and/or BRCA mutation. We collected demographic, breast cancer risk factor, and clinical data, including prior or current anti-estrogen use, type of anti-estrogen, and duration of use, from a self-administered questionnaire and medical chart review. We dichotomized anti-estrogen use as ever/never. One reader measured MD from digital images using a semiautomated computer-assisted technique with Cumulus software. MD was determined for a baseline mammogram (within 6 months of starting an anti-estrogen), a short-term follow-up (12-24 months) and/or a long-term follow-up (48-60 months) mammogram. We conducted multivariable logistic regression models to assess the association between change in MD over time with and without anti-estrogen use for chemoprevention.
Results:
Of 190 evaluable women, 86 (45%) women took an anti-estrogen (53 tamoxifen, 25 raloxifene, 4 AI, 4 multiple anti-estrogens) and 104 (55%) did not. Compared to women who did not take an anti-estrogen, those who took chemoprevention were more likely to be older (age 56 vs. 53 years), postmenopausal (65% vs. 51%), have a higher body mass index [BMI] (28.2 vs. 26.8 kg/m2), and had a lower mean baseline MD (12.7% vs. 15.9%). Comparing high-risk women who initiated anti-estrogens to those who did not, mean absolute short-term change in MD (SD) was -0.249% (SD 6.22) vs .057% (10.16) and mean long-term change in MD was -3.25% (8.25) vs. -4.19% (11.98), respectively. There was no significant short-term change in breast density with chemoprevention; however, women who took chemoprevention were 4 times more likely to have at least a 5% decrease in breast density compared to those who did not take chemoprevention after adjustment for age, menopausal status, and baseline MD (OR=4.14, 95% CI=1.03-16.73).
Discussion:
Among high-risk women who initiated anti-estrogens, we did not observe a significant short-term change in MD, but chemoprevention uptake was associated with a significant decrease in MD with long-term follow-up. Our data suggests that short-term changes in MD with chemoprevention may be too small to be detected by current methods, therefore other risk biomarkers may be needed to assess short-term response to anti-estrogens.
Citation Format: Namburi S, Coe AM, Thomas P, Hershman D, Sandoval R, Maria A, Crew KD. Effect of chemoprevention uptake on mammographic density over time in women at high risk for breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-09.