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Open Access Highly Accessed Research article

Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study

Rahul Roychoudhuri1, David Robinson1*, Venkata Putcha1, Jack Cuzick2, Sarah Darby3 and Henrik Møller14

Author Affiliations

1 King's College London, Thames Cancer Registry, 1st Floor Capital House, 42 Weston Street, London SE1 3QD, UK

2 Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Charterhouse Square, London EC1M 6BQ, UK

3 Clinical Trial Service Unit and Epidemiological Studies Unit, Radcliffe Infirmary, Oxford OX2 6HE, UK

4 London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK

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BMC Cancer 2007, 7:9  doi:10.1186/1471-2407-7-9

Published: 15 January 2007

Abstract

Background

Breast radiotherapy as practised in the 1970s and 1980s resulted in significant myocardial exposure, and this was higher when the left breast was treated. It has been proposed that this difference might result in greater cardiovascular mortality following irradiation of the left breast when compared with the right.

Methods

All cases of female breast cancer diagnosed between 1971 and 1988 and recorded on the Thames Cancer Registry database were followed up to the end of 2003 to identify cases who had died from ischaemic heart disease (IHD) or any cardiovascular disease (CVD). A proportional hazards regression analysis was performed, stratified by time since diagnosis, using as the baseline group those women with right-sided disease who did not receive radiotherapy, and adjusting for age at diagnosis.

Results

A total of 20,871 women with breast cancer were included in the analysis, of which 51% had left-sided disease. Mortality at 15+ years after diagnosis was increased in recipients of left-breast radiotherapy compared to non-irradiated women with right-sided breast cancer, both for IHD (hazard ratio 1.59; 95% confidence interval 1.21–2.08; p = 0.001) and all CVD (hazard ratio 1.27; 95% confidence interval 1.07–1.51; p = 0.006). When irradiated women with left-sided breast cancer were compared with irradiated women with right-sided breast cancer, cardiovascular mortality at 15+ years after diagnosis was raised by around 25% (IHD: hazard ratio 1.23; 95% confidence interval 0.95–1.60; p = 0.114; CVD: hazard ratio 1.25; 95% confidence interval 1.05–1.49; p = 0.014).

Conclusion

We have found an elevation in cardiovascular mortality more than 15 years after breast radiotherapy in women diagnosed with breast cancer between 1971 and 1988. The risk was greater following irradiation of the left breast compared with the right. This confirms that radiotherapy as practised in the 1970s and 1980s has resulted in significant long-term cardiac toxicity. In absolute terms, the increase in cardiovascular mortality induced by radiotherapy may be substantial, as these mortality events are relatively common.