© The Author 2007. Published by Oxford University Press.
ARTICLES |
Long-Term Risk of Cardiovascular Disease in 10-Year Survivors of Breast Cancer
Affiliations of authors: Departments of Epidemiology (MJH, AB, FEVL) and Radiation Oncology (BMPA, HB), Netherlands Cancer Institute, Amsterdam, The Netherlands; Departments of Radiation Oncology (MHAB) and Medical Oncology (JGMK), Erasmus Medical Center, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands; Clinical Trial Service Unit, University of Oxford, Oxford, UK (CWT)
Correspondence to: Flora E. van Leeuwen, PhD, Department of Epidemiology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands (e-mail: f.v.leeuwen{at}nki.nl).
Background: Radiotherapy for breast cancer as delivered in the 1970s has been associated with increased risk of cardiovascular disease, but recent studies of associations with modern regimens have been inconclusive. Few data on long-term cardiovascular disease risk according to specific radiation fields are available, and interaction with known cardiovascular risk factors has not been examined.
Methods: We studied treatment-specific incidence of cardiovascular disease in 4414 10-year survivors of breast cancer who were treated from 1970 through 1986. Risk of cardiovascular disease in these patients was compared with general population rates and evaluated in Cox proportional hazards regression models. All statistical tests were two-sided.
Results: After a median follow-up of 18 years, 942 cardiovascular events were observed (standardized incidence ratio = 1.30, 95% confidence interval [CI] = 1.22 to 1.38; corresponding to 62.9 excess cases per 10 000 patient-years). Breast irradiation only was not associated with increased risk of cardiovascular disease. However, radiotherapy to either the left or right side of the internal mammary chain was associated with increased cardiovascular disease risk for the treatment period 1970–1979 (for myocardial infarction, hazard ratio [HR] = 2.55, 95% CI = 1.55 to 4.19; P<.001; for congestive heart failure, HR = 1.72, 95% CI = 1.22 to 2.41; P = .002) compared with no radiotherapy. Among patients who received internal mammary chain radiotherapy after 1979, risk of myocardial infarction declined over time toward unity, whereas the risks of congestive heart failure (HR = 2.66, 95% CI = 1.27 to 5.61; P = .01) and valvular dysfunction (HR = 3.17, 95% CI = 1.90 to 5.29; P<.001) remained increased. Patients who underwent radiotherapy plus adjuvant chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) after 1979 had a higher risk of congestive heart failure than patients who were treated with radiotherapy only (HR = 1.85, 95% CI = 1.25 to 2.73; P = .002). Smoking and radiotherapy together were associated with a more than additive effect on risk of myocardial infarction (HR = 3.04, 95% CI = 2.03 to 4.55; P for departure from additivity = .039).
Conclusions: Radiotherapy as administered from the 1980s onward is associated with an increased risk of cardiovascular disease. Irradiated breast cancer patients should be advised to refrain from smoking to reduce their risk for cardiovascular disease.
| CONTEXT AND CAVEATS Prior knowledge Radiation treatment for breast cancer received in the 1970s has been associated with increased risk of cardiovascular disease, but studies of modern regimens have been inconclusive. Study design Ten-year breast cancer survivors who were treated from 1970 through 1986 were followed for treatment-specific incidence of cardiovascular disease. Rates were compared with rates in the general population. Contribution Radiotherapy to the internal mammary chain was associated with increased risk of cardiovascular disease among women who were treated from 1970 through 1979. Among women who received internal mammary chain irradiation from 1980 through 1986, the risk of myocardial infarction declined with time, but risks of valvular dysfunction and congestive heart failure remained increased. Radiation with adjuvant chemotherapy from 1980 through 1986 was associated with higher risk of congestive heart failure than radiotherapy alone. Smoking was associated with a more than additive increased risk for myocardial infarction over radiotherapy alone. Implications Radiotherapy for breast cancer administered from 1980 may be associated with an increased risk of cardiovascular disease; smoking may be associated with additional risk. Limitations The study group and the referent population may have different baseline risks for cardiovascular disease due to behavior and socioeconomic status; differences may also exist between the surgery-only referent group and the study groups. The dose of radiation to the heart could not be determined from the data available.
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Manuscript received February 3, 2006; revised December 19, 2006; accepted January 19, 2007.
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J Natl Cancer Inst 2007 99: 340-341.
J Natl Cancer Inst 2007 99: 337.
J Natl Cancer Inst 2007 99: 337.
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