Risk of Cardiovascular Disease in Women With and Without Breast Cancer: The Pathways Heart Study

Abstract

Purpose: To examine cardiovascular disease (CVD) and mortality risk in women with breast cancer (BC) by cancer therapy received relative to women without BC.

Methods: The study population comprised Kaiser Permanente Northern California members. Cases with invasive BC diagnosed from 2005 to 2013 were matched 1:5 to controls without BC on birth year and race/ethnicity. Cancer treatment, CVD outcomes, and covariate data were from electronic health records. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs of CVD incidence and mortality by receipt of chemotherapy treatment combinations, radiation therapy, and endocrine therapy.

Results: A total of 13,642 women with BC were matched to 68,202 controls without BC. Over a 7-year average follow-up (range < 1-14 years), women who received anthracyclines and/or trastuzumab had high risk of heart failure/cardiomyopathy relative to controls, with the highest risk seen in women who received both anthracyclines and trastuzumab (HR, 3.68; 95% CI, 1.79 to 7.59). High risk of heart failure and/or cardiomyopathy was also observed in women with BC with a history of radiation therapy (HR, 1.38; 95% CI, 1.13 to 1.69) and aromatase inhibitor use (HR, 1.31; 95% CI, 1.07 to 1.60), relative to their controls. Elevated risks for stroke, arrhythmia, cardiac arrest, venous thromboembolic disease, CVD-related death, and death from any cause were also observed in women with BC on the basis of cancer treatment received.

Conclusion: Women with BC had increased incidence of CVD events, CVD-related mortality, and all-cause mortality compared with women without BC, and risks varied according to the history of cancer treatment received. Studies are needed to determine how women who received BC treatment should be cared for to improve cardiovascular outcomes.

FIG 1.

Selection of BC case and matched controls for the Pathways Heart Study. ^aEight cases matched to four controls; all remaining cases matched to five controls. AJCC, American Joint Committee on Cancer; BC, breast cancer; KPNC, Kaiser Permanente Northern California.

FIG 2.

Ten-year cumulative incidence rate curves of (A, left column) ischemic heart disease, (B, middle column) heart failure and/or cardiomyopathy, and (C, right column) stroke in breast cancer cases according to combinations of chemotherapy drugs received compared with age and race/ethnicity-matched controls without breast cancer. Statistically significant differences were determined with the log-rank test.

FIG 3.

Ten-year cumulative incidence rate curves of (A, left column) ischemic heart disease, (B, middle column) heart failure and/or cardiomyopathy, and (C, right column) stroke in breast cancer cases by receipt of aromatase inhibitors, tamoxifen, left-sided radiation, and radiation (either side) treatment compared with age and race/ethnicity-matched controls without breast cancer. Statistically significant differences were determined with the log-rank test.