Abstract A32: Patterns of longitudinal change in mammographic density among tamoxifen users
Authors: Nyante Sarah J. , Sherman Mark E. , Pfeiffer Ruth M. , Berrington Amy , Brinton Louise A. , Bowles Erin Aiello , Hoover Robert N. , Glass Andrew G. , Gierach Gretchen L. 
Published: May 2019

Introduction: Tamoxifen, a selective estrogen receptor (ER) modulator, reduces breast cancer risk and is associated with improved survival after ER+ breast cancer. Prior data show that mammographic density, a potential biosensor of tamoxifen's effect, declines 1-2 years after starting tamoxifen and that declines are associated with lower breast cancer risk and recurrence. Prior studies characterizing density decline in tamoxifen users have focused on measurements from two time points. Therefore, we examined serial density measurements in breast cancer patients who took tamoxifen for varying durations to assess whether patterns of change over a longer period provide additional information.

Methods: Kaiser Permanente Northwest (KPNW) Health Plan patients who were diagnosed with ER+ breast cancer between 1990-2008, alive for ≥5 years post-diagnosis, and had ≥5 post-diagnostic mammograms of the unaffected breast were sampled according to duration of tamoxifen use and age: 2-3 years tamoxifen and ≥50 years (N=5) or &gt;50 years (N=9); ≥4 years tamoxifen and ≥50 years (N=14) or &gt;50 years (N=12). Pre-diagnostic (T0) and 5 post-diagnostic (T1 to T5) mammograms taken at approximately yearly intervals were digitized to assess quantitative total breast area and dense area using computerized thresholding (intraclass correlation coefficients for masked duplicate readings: breast area=0.99; dense area=0.95).

Percent density was calculated as the ratio of dense area to total breast area. Change in density was calculated as density (at T1 to T5) minus density at T0. Mean changes and standard deviations (SD) were calculated, overall and stratified by years of tamoxifen and/or density at T0 (tertiles: ≥15.4%; 15.5 -32.1%; &gt;32.1%). Differences in density change were tested using the Mann-Whitney test and age-adjusted linear models. Differences by time and duration of tamoxifen use were estimated by including an interaction between tamoxifen use and time. Correlations from repeated measurements on the same woman were accounted for using generalized estimating equations methods.

Results: Patients were aged 40 to 77 years at diagnosis. The mean mammographic density change at T1 was -4.5% (SD 11.4) and at T4 -6.8% (SD 12.1). At T4, density decline was slightly greater among current users of tamoxifen (-7.8%, SD 12.9) compared with women who stopped after 2-3 years (-4.9%, SD 10.6; P=0.64). Density declines were greatest among women in the highest tertile of density at T0 (-16.0% [SD 15.5] at T4) compared with middle (-4.6% [SD 8.7]) and lowest tertiles (-0.6% [SD 5.2])(P&lt;0.01). Among those in the highest density tertile, larger changes occurred from T0 to T1 (mean -14.9%) than in later years (additional -3.6% by T5). Most of the decline occurred early for both 2-3 year and ≥4 year users. ≥4 year users showed small declines through T5 while 2-3 year users did not, but differences were not statistically significant in linear models (P=0.88).

Conclusion: Among ER+ breast cancer patients treated with tamoxifen, the largest declines in mammographic density occurred after one year of treatment. Small declines continued with use, but were not significantly different from changes in patients who stopped tamoxifen. This suggests that single density measures approximately one year post-tamoxifen initiation are generally representative of longer-term changes; however, this analysis was restricted to patients surviving ≥5 years. Patterns were not assessed among patients who died within 5 years or in the chemoprevention setting. These data suggest that assessment of tissue effects within the first year of tamoxifen therapy may provide mechanistic insights into the relationships between tamoxifen, density and breast cancer outcomes.

Citation Format: Sarah J. Nyante, Mark E. Sherman, Ruth M. Pfeiffer, Amy Berrington, Louise A. Brinton, Erin Aiello Bowles, Robert N. Hoover, Andrew G. Glass, Gretchen L. Gierach. Patterns of longitudinal change in mammographic density among tamoxifen users. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A32.