Abstract PD5-01: Cardiovascular disease risk of breast cancer therapies: The pathways heart study
Authors: Greenlee Heather , Rillamas-Sun Eileen , Iribarren Carlos , Cheng Richard , Neugebauer Romain , Rana Jamal S. , Nguyen-Huynh Mai , Shi Zaixing , Laurent Cecile A. , Lee Valerie S. , Roh Janise M. , Shen Hanjie , Hershman Dawn L. , Kushi Lawrence H. , Kwan Marilyn L. 
Published: March 2022

Purpose: Studies on long-term cardiovascular disease (CVD) risk in breast cancer (BC) survivors are limited. We examined CVD risk associated with exposure to specific BC therapies and explored whether body mass index (BMI) or prevalent CVD risk factors at BC diagnosis modified these associations. Methods: The Pathways Heart Study is a prospective cohort study examining incident CVD outcomes and risk factors in women with BC at Kaiser Permanente Northern California (KPNC). Eligible women were diagnosed with stage I-IV invasive BC from 2005-2013, &ge;21 years old, and KPNC members &ge;12 months at diagnosis. KPNC records provided demographic and BC therapy characteristics. Incident CVD outcomes [ischemic heart disease, heart failure/cardiomyopathy (HF/CM), stroke] were assessed from ICD9/10 codes. Multivariable Cox models estimated hazard ratios (HR) and 95% confidence intervals (CI) of each CVD outcome by cancer therapy received compared to not receiving that therapy, excluding those with prevalent CVD. Separate regression models included interaction terms for cancer therapy by overweight, obesity, diabetes, dyslipidemia, and hypertension to test whether the CVD outcome risk varied by presence of these factors at diagnosis. Results: Among 4,181 BC survivors with mean age of 59.6±12.0 years and mean follow-up of 7.9±3.5 years (range: 0.04-13.3), cancer therapies were not associated with incident CVD. However, CVD risks varied by BMI and prevalence of CVD risk factors at BC diagnosis. Normal weight (NW) women who received anthracyclines had higher risk of ischemic heart disease and HF/CM relative to NW women not receiving these therapies; interaction terms indicated HF/CM risk was statistically different than risks for obese women (Table). NW women who received cyclophosphamide or left-sided radiation had higher risk of HF/CM and stroke relative to NW women not receiving these therapies; these risks were statistically different from obese (for cyclophosphamide) or overweight (for radiation) women. Relative to women not receiving these therapies, higher HRs for HF/CM were observed among non-diabetic women who received cyclophosphamide (2.03, CI: 1.22-3.37), non-dyslipidemic women who received anthracyclines (3.65, CI: 1.69-7.87), and non-hypertensive women who received either anthracyclines (4.04, CI: 1.81-9.03) or cyclophosphamide (2.66, CI: 1.23-5.74) (P for interaction range: 0.04 to 0.06). Conclusion: Certain chemotherapy drugs may increase the risk of CVD in NW BC survivors; overweight and obese BC survivors may experience less risk than NW women. While chemotherapy also appears to increase HF/CM risk for women without diabetes, dyslipidemia, and hypertension, these conditions are more prevalent among overweight/obese women. Analysis within these subgroups is needed and forthcoming.

Table. Adjusted HRs (95% CI) of CVD outcomes among breast cancer survivors receiving select cancer therapies* stratified by BMI status at diagnosisBMI Ischemic heart diseaseHeart failure/CardiomyopathyStrokeAnthracycline, n=1283Normal4.22 (1.59, 11.2)5.27 (2.54, 10.9)1.89 (0.79, 4.53)Overweight1.66 (0.73, 3.77)2.17 (1.15, 4.11)0.40 (0.16, 0.99)Obese1.26 (0.56, 2.85)1.1 (0.54, 2.27)a0.33 (0.13, 0.83)aCyclophosphamide, n=1705Normal1.63 (0.61, 4.31)3.28 (1.59, 6.75)2.21 (1.01, 4.84)Overweight1.59 (0.75, 3.39)1.63 (0.9, 2.97)0.73 (0.34, 1.58)Obese0.85 (0.39, 1.86)0.75 (0.38, 1.47)a0.31 (0.13, 0.71)aLeft-Side Radiation, n=1331Normal1.44 (0.56, 3.69)2.04 (1.0, 4.18)2.38 (1.28, 4.42)Overweight1.47 (0.68, 3.16)0.68 (0.34, 1.34)b0.72 (0.37, 1.4)bObese1.32 (0.73, 2.38)1.30 (0.79, 2.16)1.05 (0.61, 1.82)*Cancer therapies with non-significant findings (i.e., Trastuzumab, taxanes, aromatase inhibitors, Tamoxifen, and any-side radiation) are not shown.ap≤0.05 normal weight v. obese; bp≤0.05 normal weight v. overweight

Citation Format: Heather Greenlee, Eileen Rillamas-Sun, Carlos Iribarren, Richard Cheng, Romain Neugebauer, Jamal S. Rana, Mai Nguyen-Huynh, Zaixing Shi, Cecile A. Laurent, Valerie S. Lee, Janise M. Roh, Hanjie Shen, Dawn L. Hershman, Lawrence H. Kushi, Marilyn L. Kwan. Cardiovascular disease risk of breast cancer therapies: The pathways heart study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-01.