Abstract PD4-2: Cardiovascular toxicity following aromatase inhibitor use in 13,273 survivors cared for in a HMO
Authors: Haque Reina , Schottinger Joanne E , Shi Jiaxiao , Chung Joanie , Avila Chantal , Amundsen Britta , Chlebowski Rowan T 
Published: May 2015

Abstract
Background
Aromatase inhibitors (AIs) reduce breast cancer incidence in primary prevention trials (MAP3, IBIS2). However, controversy regarding AI’s influence on cardiovascular disease (MI, angina, and cardiac failure) (Amir et al JNCI 2011) could limit use in prevention settings.
Methods
We assembled a cohort of 13,273 postmenopausal breast cancer patients initially CVD (cardiovascular disease)-free at diagnosis in a large managed care organization. Women were diagnosed 1991-2010, and followed through 2012. The outcome, CVD risk was compared across endocrine treatments (AI, tamoxifen [TAM], both, or neither). Information on demographics, comorbidity (diabetes, hypertension, etc.), and covariate medications (antihyperlipidemics, antihypertensives, and other CVD drugs) were available from electronic medical records. We conducted Cox models using time-dependent endocrine drug use variables adjusted for age, demographics, comorbidity, and CVD drug use, cancer treatment, tumor characteristics and tumor laterality.
Results
Among the 13,273 cohort, postmenopausal women who used AIs exclusively had a similar risk of ischemic disease (HR=0.97, 95% CI: 0.78-1.22) and stroke (HR=0.97, 95% CI: 0.70-1.33) versus those who used TAM only (HR=1.00, reference). However, women who used AIs only had a higher risk of other CVD disease combined (CHF, cardiomyopathy, dysrthymia, valvular dysfunction, pericarditis) (HR=1.26, 95% CI: 1.11-1.43) than those exposed to TAM only. The risk of other CVD disease was greater among women exposed to sequential TAM and AI treatment. The results are based on 3,711 CVD events occurring in 72,886 woman-years of follow-up.
Tamoxifen OnlyAI OnlyBoth Tam and AINo HormonesHR (95% Cl)HR (95% Cl)HR (95% Cl)HR (95% Cl)MUTUALLY EXCLUSIVE CATEGORIESIschemic1.00 (ref)0.97 (0.78 - 1.22)1.04 (0.83 - 1.29)1.02 (0.84 - 1.23)Stroke1.00 (ref)0.97 (0.70 - 1.33)1.02 (0.75 - 1.37)0.93 (0.70 - 1.24)Other CVD1.00 (ref)1.26 (1.11 - 1.43)1.28 (1.13 - 1.44)1.23 (1.09 - 1.38)COMPOSITE CVD1.00 (ref)1.15 (1.04 - 1.28)1.19 (1.07 - 1.31)1.14 (1.04 - 1.25)
Based on a subset of 7,982 patients who underwent breast irradiation, the risk of CVD overall was greater among women who used AIs only and received left-sided irradiation (HR=1.21, 95% CI: 1.02-1.44).
Tamoxifen OnlyAI OnlyBoth Tam and AINo HormonesHR (95% Cl)HR (95% Cl)HR (95% Cl)HR (95% Cl)Right-sided breast irradiationCOMPOSITE CVD1.00 (ref)1.16 (1.00 - 1.34)1.20 (1.04 - 1.38)1.08 (0.95 - 1.23)Left-sided breast irradiationCOMPOSITE CVD1.00 (ref)1.21 (1.02 - 1.44)1.16 (0.98 - 1.37)1.14 (0.93 - 1.40)
Discussion
These results indicate that variation exists in the type of CVD events that occur in breast cancer patients receiving AIs in comparison to tamoxifen users. For example, the risk of ischemic disease or stroke was not elevated in those who used AIs only versus TAM users. However, overall CVD events were greater in women who used AIs only (or sequentially after TAM), especially if they received left-sided breast irradiation. While these observational study results require cautious interpretation, they provide a basis for comparing the benefits and risks of endocrine treatments.
Citation Format: Reina Haque, Joanne E Schottinger, Jiaxiao Shi, Joanie Chung, Chantal Avila, Britta Amundsen, Rowan T Chlebowski. Cardiovascular toxicity following aromatase inhibitor use in 13,273 survivors cared for in a HMO [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD4-2.