Risk of cardiac death after adjuvant radiotherapy for breast cancer.

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.

[1]  A. Polednak.  Trends in, and predictors of, breast-conserving surgery and radiotherapy for breast cancer in Connecticut, 1988-1997. , 2002, International journal of radiation oncology, biology, physics.

[2]  L. Rutqvist,et al.  Myocardial infarction among women with early-stage breast cancer treated with conservative surgery and breast irradiation. , 1998, International journal of radiation oncology, biology, physics.

[3]  W. Mackillop,et al.  Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  M Baum,et al.  Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  J. Vermorken.  Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials , 2000, The Lancet.

[6]  L. Rutqvist,et al.  Mortality by laterality of the primary tumour among 55,000 breast cancer patients from the Swedish Cancer Registry. , 1990, British Journal of Cancer.

[7]  M. Overgaard.  Postoperative radiotherapy in high-risk postmenopausal breast cancer , 1999, The Lancet.

[8]  H. Johansson,et al.  Adjuvant radiation therapy versus surgery alone in operable breast cancer: long-term follow-up of a randomized clinical trial. , 1993, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[9]  I. Lax,et al.  Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer. , 1992, International journal of radiation oncology, biology, physics.

[10]  J. Haybittle,et al.  Cardiac doses in post-operative breast irradiation. , 1992, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[11]  J. Overgaard,et al.  Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials , 1999, The Lancet.

[12]  J. Tarkkanen,et al.  Adjuvant postoperative radiotherapy, chemotherapy, and immunotherapy in stage III breast cancer , 1984, Cancer.

[13]  J. Samet,et al.  Geographic variation in the treatment of localized breast cancer. , 1992, The New England journal of medicine.

[14]  A. Dobson,et al.  Death certification and coding for ischemic heart disease in Australia. , 1983, American journal of epidemiology.

[15]  S. Bentzen,et al.  The value of the NSD formula in equation of acute and late radiation complications in normal tissue following 2 and 5 fractions per week in breast cancer patients treated with postmastectomy irradiation. , 1987, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[16]  S. Wing,et al.  United States mortality from ill-defined causes, 1968-1988: potential effects on heart disease mortality trends. , 1995, International journal of epidemiology.

[17]  P. Douglas,et al.  Assessment of coronary heart disease morbidity and mortality after radiation therapy for early breast cancer. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  J. Overgaard,et al.  Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials. Radiotherapy Committee of the Danish Breast Cancer Cooperative Group. , 1999, Lancet.

[19]  J. Manola,et al.  No long-term increase in cardiac-related mortality after breast-conserving surgery and radiation therapy using modern techniques. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  D. Hollis,et al.  Symptomatic cardiac events following radiation therapy for left-sided breast cancer: possible association with radiation therapy-induced changes in regional perfusion. , 2003, Clinical breast cancer.

[21]  G Noël,et al.  [Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials]. , 2001, Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique.

[22]  Mike Clarke,et al.  Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials , 2000 .

[23]  Lawrence B Marks,et al.  Myocardial perfusion changes in patients irradiated for left-sided breast cancer and correlation with coronary artery distribution. , 2001, International journal of radiation oncology, biology, physics.

[24]  Gregory S. Cooper,et al.  Studying Radiation Therapy Using SEER-Medicare-Linked Data , 2002, Medical care.

[25]  K. Zedeler,et al.  Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. , 1997, The New England journal of medicine.

[26]  C. Redmond,et al.  Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. , 1995, New England Journal of Medicine.

[27]  J. Goodwin,et al.  Information on radiation treatment in patients with breast cancer: the advantages of the linked medicare and SEER data. Surveillance, Epidemiology and End Results. , 1999, Journal of clinical epidemiology.

[28]  W. Mackillop,et al.  Mortality from myocardial infarction following postlumpectomy radiotherapy for breast cancer: a population-based study in Ontario, Canada. , 1999, International journal of radiation oncology, biology, physics.

[29]  P. Hall,et al.  Mortality from cardiovascular disease more than 10 years after radiotherapy for breast cancer: nationwide cohort study of 90 000 Swedish women , 2003, BMJ : British Medical Journal.

[30]  N. Le,et al.  Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. , 1997, The New England journal of medicine.

[31]  J. Haybittle,et al.  Postoperative radiotherapy and late mortality: evidence from the Cancer Research Campaign trial for early breast cancer. , 1989, BMJ.