Cardiac morbidity
Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden

https://doi.org/10.1016/j.radonc.2011.06.016Get rights and content

Abstract

Purpose

To study incidence of radiation-related heart disease in a large population of breast cancer patients followed for up to 30 years.

Material and methods

72,134 women diagnosed with breast cancer in Denmark or Sweden during 1976–2006 and followed prospectively. Radiation-related risk was studied by comparing women with left-sided and right-sided tumours.

Results

34,825 women (48%) received radiotherapy. Among unirradiated women tumour laterality had little relevance to heart disease. Among irradiated women mean dose to the whole heart was 6.3 Gy for left-sided tumours and 2.7 Gy for right-sided tumours. Mortality was similar in irradiated women with left-sided and right-sided tumours, but incidence ratios, left-sided versus right-sided, were raised: acute myocardial infarction 1.22 (95% CI 1.06–1.42), angina 1.25 (1.05–1.49), pericarditis 1.61 (1.06–2.43), valvular heart disease 1.54 (1.11–2.13). Incidence ratios for all heart disease were as high for women irradiated since 1990 (1.09 [1.00–1.19]) as for women irradiated during 1976–1989 (1.08 [0.99–1.17]), and were higher for women diagnosed with ischaemic heart disease prior to breast cancer than for other women (1.58 [1.19–2.10] versus 1.08 [1.01–1.15], p for difference = 0.01).

Conclusions

Breast cancer radiotherapy has, at least until recently, increased the risk of developing ischaemic heart disease, pericarditis and valvular disease. Women with ischaemic heart disease before breast cancer diagnosis may have incurred higher risks than others.

Section snippets

Materials

Since the late 1970s, the Danish Breast Cancer Cooperative Group has recorded details of all women diagnosed with breast cancer in Denmark [6], while in Sweden the Stockholm and Umeå Breast Cancer Care Programs have done likewise for women in their catchment areas. Lists of women with breast cancer were cross-matched with the Danish hospital-inpatient and outpatient registers [7] and with the Swedish national patient register [8], and the main diagnosis was obtained for each discharge. These

Characteristics of study population

Overall 48% of the 72,134 women in the study received radiotherapy (Table 1). This percentage varied by country, with calendar year of breast cancer diagnosis, age at breast cancer diagnosis, and whether or not the woman received breast-conserving surgery, hormonal therapy or chemotherapy (p < 0.00001 for all differences). For each of these characteristics the percentage of women irradiated was virtually identical for left-sided and right-sided breast cancer. Only for the few women known to have

Discussion

This is the first large population-based study of the incidence of radiation-related heart disease in women with breast cancer for which cardiac dose estimates are available. Women with left-sided breast cancer received substantial cardiac doses, with mean dose to the whole heart above 5 Gy and mean dose to the LAD coronary artery above 15 Gy throughout the study period, while for women with right-sided breast cancer mean dose to the whole heart was lower, in the range 2–4 Gy, and mean dose to the

Conflict of Interest

The authors declare that they have no financial or personal relationships with other people or organisations that could inappropriately influence their work.

Funding sources

This study was funded by the European Commission (Grant FI6R-012796), the UK Department of Health (Grant RRX 108), the British Heart Foundation (CRE Grant RE/08/004) and by Cancer Research UK (Grant to CTSU). The funders had no role in the study design, the data collection, the analysis and interpretation of the data, in the writing of the manuscript, or in the decision to submit for publication.

Acknowledgements

We thank Jill Boreham for calculating the national mortality rates and many colleagues for helpful discussions and comments on earlier drafts of this paper.

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