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


CONCLUSIONS
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.
Roychoudhuri
Rahul
R
King's College London, Thames Cancer Registry, 1st Floor Capital House, 42 Weston Street, London SE1 3QD, UK. r.roychoudhuri@gen.cam.ac.uk <r.roychoudhuri@gen.cam.ac.uk>
Robinson
David
D
Putcha
Venkata
V
Cuzick
Jack
J
Darby
Sarah
S
Møller
Henrik
H
D000368:Aged; D001943:Breast Neoplasms / Q000532:radiotherapy*; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000528:radiation effects; D006801:Humans; D008875:Middle Aged; D011832:Radiation Injuries / Q000401:mortality*; D013997:Time Factors