Abstract 5303: Cardiovascular disease risk associated with breast cancer chemotherapy drugs: The Pathways Heart Study
Authors: Shen Hanjie , Rillamas-Sun Eileen , Iribarren Carlos , Cheng Richard , Rana Jamal S. , Nguyen-Huynh Mai , Laurent Cecile A. , Lee Valerie S. , Roh Janise M. , Hershman Dawn L. , Kushi Lawrence H. , Kwan Marilyn L. , Greenlee Heather 
Published: June 2022

Abstract
Purpose: Chemotherapy drugs to treat breast cancer (BC) are cardiotoxic, but few studies have examined the effects of specific chemotherapy combinations on cardiovascular disease (CVD). We examined the additive effects of combinations of BC chemotherapy drugs associated with incident CVD events among women with a history of BC compared to those without.
Methods: The Pathways Heart Study is a cohort study within Kaiser Permanente Northern California (KPNC) examining incident CVD events and risk factors in women with BC. Eligibility criteria included invasive BC diagnosis from 11/2005 to 3/2013, age&ge;21 years, and KPNC membership&ge;12 months at BC diagnosis. Controls without BC were matched 5:1 on birth year and race/ethnicity. KPNC electronic health records were used to collect demographic, clinical, and treatment characteristics. Chemotherapy drugs identified from clinical data included anthracyclines, cyclophosphamides, taxanes, and trastuzumab. Mutually exclusive groups were created according to the types of chemotherapy drugs received. Outcomes identified from ICD9/10 diagnosis codes included incident ischemic heart disease, heart failure (HF)/cardiomyopathy and stroke. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of the CVD outcome by chemotherapy drug combinations received relative to matched controls.
Results: A total of 6,761 women with BC who received chemotherapy were identified and were matched to 33,801 controls. On average, women were 55.2 years old (standard deviation (SD)=10.9) and were followed for 7.1 years (SD=3.6). Four groups of women with distinct chemotherapy combinations were identified: anthracyclines + cyclophosphamide (AC, 10.5%), AC + taxanes (39.0%), AC + taxanes + trastuzumab (8.8%), and cyclophosphamide + taxanes (20.7%). Women who received AC had a 2.00 (95% CI: 1.27-3.14) increased risk of incident HF/cardiomyopathy relative to matched controls without BC. When taxanes were added to this combination, risk was similar (HR=1.88; 95% CI: 1.44-2.47). However, when trastuzumab was further added, risk of HF/cardiomyopathy increased more than 1.5-fold (HR=3.18; 95% CI: 1.91-5.30). The combined receipt of cyclophosphamide and taxanes was associated with a 1.42 (95% CI: 1.05-1.92) increased risk of developing stroke, but including anthracyclines with this combination inversed the association for stroke (HR: 0.73, 95% CI: 0.54- 0.99). No combinations examined were associated with incidence of ischemic heart disease.
Conclusion: Findings suggest specific chemotherapy drug combinations may differentially affect the risk of incident HF/cardiomyopathy and stroke in BC survivors. Future work will examine dosage and duration of chemotherapy exposure, comparisons of the groups’ characteristics to account for possible confounding by indication, and competing risk analysis.
Citation Format: Hanjie Shen, Eileen Rillamas-Sun, Carlos Iribarren, Richard Cheng, Jamal S. Rana, Mai Nguyen-Huynh, Cecile A. Laurent, Valerie S. Lee, Janise M. Roh, Dawn L. Hershman, Lawrence H. Kushi, Marilyn L. Kwan, Heather Greenlee. Cardiovascular disease risk associated with breast cancer chemotherapy drugs: The Pathways Heart Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5303.