Risk of cardiac death after adjuvant radiotherapy for breast cancer

Abstract

Background: Women with breast cancer who are treated with adjuvant radiation have a decreased risk of local recurrence but an increased risk of mortality from ischemic heart disease. Patients with left-sided breast tumors receive a higher dose of radiation to the heart than patients with right-sided tumors. Because radiation techniques have improved over time, we investigated whether the risk of death from ischemic heart disease after adjuvant breast radiotherapy decreased over time.

Methods: We used the 12-registry 1973-2000 dataset from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Women (n = 27,283) treated with adjuvant radiation for breast cancer diagnosed in 1973-1989 were included in the study. Ischemic heart disease mortality was calculated at 15 years and compared for women diagnosed during 1973-1979, 1980-1984, and 1985-1989. Cox proportional hazards models were used to calculate the hazard of death from ischemic heart disease for women diagnosed 1973-1988 and censored at 12 years. All statistical tests were two-sided.

Results: There were no differences in age, race/ethnicity, disease stage, or follow-up time between the 13 998 women with left-sided and 13 285 with right-sided cancer. For women diagnosed in 1973-1979, there was a statistically significant difference in 15-year mortality from ischemic heart disease between patients with left-sided (13.1%, 95% confidence interval [CI] = 11.6 to 14.6) and those with right-sided (10.2%, 95% CI = 8.9 to 11.5) breast cancer (P = .02); no such difference was found for women diagnosed in 1980-1984 (9.4%, [95% CI = 8.1 to 10.6] versus 8.7% [95% CI = 7.4 to 10.0], respectively, P = .64) or 1985-1989 (5.8% [95% CI = 4.8 to 6.8] versus 5.2% [95% CI = 4.4 to 5.9], respectively, P = .98). In the Cox model, the hazard ratio [HR] for ischemic heart disease mortality for women with left-sided versus women with right-sided disease was 1.50 (95% CI = 1.19 to 1.87) in 1979. With each succeeding year after 1979, the hazard of death from ischemic heart disease for women with left-sided versus those with right-sided disease declined by 6% (HR = 0.94, 95% CI = 0.91 to 0.98).

Conclusions: Risk of death from ischemic heart disease associated with radiation for breast cancer has substantially decreased over time.

Fig. 1

Kaplan–Meier survival curves by breast cancer laterality and year of diagnosis. Mean time of follow-up was 96 months, 113 months, and 121 months for patients diagnosed in 1973–1979, 1980–1984, and 1985–1989, respectively. Broken lines = patients with right-sided breast cancer; solid lines = patients with left-sided breast cancer; blue lines = 1973–1979 cohort; red lines = 1980–1984 cohort; green lines = 1985–1989.

Fig. 2

Kaplan–Meier survival curves by breast cancer laterality and year of diagnosis for patients with in situ and localized stage tumors. Mean time of follow-up was 121 months, 133 months, and 132 months for patients diagnosed in 1973–1979, 1980–1984, and 1985–1989, respectively. Broken lines = patients with right-sided breast cancer; solid lines = patients with left-sided breast cancer; blue lines = 1973–1979 cohort; red lines = 1980–1984 cohort; green lines = 1985–1989.

Fig. 3

Kaplan – Meier survival curves by breast cancer laterality and year of diagnosis for patients with regional-stage tumors. Mean time of follow-up was 88 months, 94 months, and 101 months for patients diagnosed in 1973– 1979, 1980 – 1984, and 1985 – 1989, respectively. Broken lines = patients with right-sided breast cancer; solid lines = patients with left-sided breast cancer; blue lines = 1973–1979 cohort; red lines = 1980–1984 cohort; green lines = 1985–1989.