Abstract P5-12-01: Adjuvant endocrine therapy and risk of contralateral breast cancer among a cohort of U.S. women with breast cancer
Authors: Gierach GL , Curtis RE , Pfeiffer RM , Mullooly M , Hoover RN , Nyante SJ , Feigelson HS , Glass AG , Berrington de Gonzalez A 
Published: May 2016

Abstract
Background: The increasing incidence of estrogen receptor (ER)-positive breast cancer in the U.S. in concert with the aging population and improved survival have resulted in an increased number of women at risk of developing a second contralateral primary breast cancer. Results from randomized clinical trials have suggested a reduced risk of contralateral breast cancer among women taking tamoxifen or aromatase inhibitors. However, little is known about the duration of beneficial effects of endocrine therapy within the context of real life treatment scenarios, where gaps in treatment and varying durations of use may influence risk.
Methods: We assessed contralateral breast cancer risk associated with adjuvant tamoxifen treatment among a cohort of 7,541 women, ages 24-85 years, who were members of Kaiser Permanente (KP) Northwest or Colorado, and were diagnosed with invasive breast cancer between 1990 and 2008 and remained at risk of contralateral breast cancer for at least one year. We also assessed risk in relation to aromatase inhibitor use, though statistical power was somewhat limited due to the relatively recent introduction of aromatase inhibitors in this older cohort. Use of tamoxifen, aromatase inhibitors and other treatments was ascertained from KP prescription and medical records. Relative risks (RR) and 95% confidence intervals (CI) were estimated using multivariable Poisson regression adjusting for study site, age at and year of diagnosis, stage at diagnosis, ER status, chemotherapy, and radiotherapy.
Results: Over a median (range) of 6.3 (1.0-20.9) years of follow-up, 248 women developed contralateral breast cancer. Among patients surviving at least five years (n=4,668), 58% were prescribed tamoxifen with a median (range) duration of use of 4.2 (0.25-16.2) years. In models evaluating joint effects of tamoxifen duration and time since last use, we observed a statistically significant reduced risk of contralateral breast cancer among current tamoxifen users (RR=0.47, 95% CI: 0.30, 0.74) and among former users with 4+ years of tamoxifen (RR=0.39, 95% CI: 0.24, 0.63) as compared with women not treated with tamoxifen. Former users with 1-4 years of tamoxifen demonstrated a suggestive reduction in risk (RR=0.71, 95% CI: 0.45, 1.10), but there was no evidence of risk reduction for former users with &lt;1 year of tamoxifen (RR=0.96, 95% CI: 0.56, 1.64). The reduced risks associated with 4+ years of tamoxifen persisted among patients surviving at least 7 years but were attenuated among those with more than 10 years since their first primary diagnosis. Aromatase inhibitor use was also associated with reduced contralateral breast cancer risk (RR=0.46, 95% CI: 0.22, 0.97). In subgroup analyses restricted to women whose first primary cancer was ER-positive (n=5,951), findings were consistent with those observed in the overall cohort.
Conclusions: Adjuvant tamoxifen and aromatase inhibitor therapy considerably reduce the risk of contralateral breast cancer. Furthermore, our data suggest that tamoxifen protects against contralateral breast cancer while women are being treated and that the protective effect appears to continue after cessation with longer durations of use.
Citation Format: Gierach GL, Curtis RE, Pfeiffer RM, Mullooly M, Hoover RN, Nyante SJ, Feigelson HS, Glass AG, Berrington de Gonzalez A. Adjuvant endocrine therapy and risk of contralateral breast cancer among a cohort of U.S. women with 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 P5-12-01.