Cardiac mortality after radiotherapy, chemotherapy and endocrine therapy for breast cancer: Cohort study of 2 million women from 57 cancer registries in 22 countries

Katherine E. Henson, Paul McGale, Sarah Darby, Max Parkin, Yaochen Wang, Carolyn W. Taylor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Comparisons of patients receiving different cancer treatments reflect the effects of both treatment and patient selection. In breast cancer, however, if radiotherapy decisions are unrelated to laterality, comparisons of left-sided and right-sided cancers can demonstrate the causal effects of higher-versus-lower cardiac radiation dose. Cardiac mortality was analysed using individual patient data for 1,934,248 women with breast cancer in 22 countries. The median date of diagnosis was 1996 and the interquartile range was 1987–2002. A total of 1,018,505 women were recorded as irradiated, 223,077 as receiving chemotherapy, 317,619 as receiving endocrine therapy and 55,264 died of cardiac disease. Analyses were stratified by time since breast cancer diagnosis, age at diagnosis, calendar year of diagnosis and country. Patient-selection effects were evident for all three treatments. For radiotherapy, there was also evidence of selection according to laterality in women irradiated 1990 or later. In patients irradiated before 1990, there was no such selection and cardiac mortality was higher in left-sided than right-sided cancer (rate ratio [RR]: 1.13, 95% confidence interval 1.09–1.17). Left-versus-right cardiac mortality RRs were greater among younger women (1.46, 1.19, 1.20, 1.09 and 1.08 after cancer diagnoses at ages <40, 40–49, 50–59, 60–69 and 70+ years, 2ptrend =0.003). Left-versus-right RRs also increased with time since cancer diagnosis (1.03, 1.11, 1.19 and 1.21 during 0–4, 5–14, 15–24 and 25+ years, 2ptrend =0.002) while for women who also received chemotherapy, the left-versus-right RR was 1.42 (95% confidence interval 1.13–1.77), compared to 1.10 (1.05–1.16) for women who did not (2pdifference= 0.03). These results show that the relative increase in cardiac mortality from cardiac exposure during breast cancer radiotherapy given in the past was greater in younger women, lasted into the third decade after exposure and was greater when chemotherapy was also given.

Original languageEnglish
Pages (from-to)1437-1449
Number of pages13
JournalInternational Journal of Cancer
Volume147
Issue number5
DOIs
Publication statusPublished - 1 Sep 2020

Bibliographical note

Funding Information:
The chief acknowledgement is to the cancer registries and other organisations, who contributed data to the study, see Table S1 for list. The authors would like to thank Dymphna Hermans for her work liaising with them. This work was funded by a research contract to the University of Oxford under the Department of Health Policy Research Programme (Studies of Ionising Radiation and the Risk of Heart Disease), by a Cancer Research UK grant (C8225/A21133) and by the British Heart Foundation Centre for Research Excellence, Oxford (grant RE/13/1/30181) as well as core funding from Cancer Research UK, the UK Medical Research Council and the British Heart Foundation to the Oxford University Clinical Trial Service Unit (grant MC_U137686858) and Department of Health, UK (091/0203).

Funding Information:
The chief acknowledgement is to the cancer registries and other organisations, who contributed data to the study, see Table S1 for list. The authors would like to thank Dymphna Hermans for her work liaising with them. This work was funded by a research contract to the University of Oxford under the Department of Health Policy Research Programme (Studies of Ionising Radiation and the Risk of Heart Disease), by a Cancer Research UK grant (C8225/A21133) and by the British Heart Foundation Centre for Research Excellence, Oxford (grant RE/13/1/30181) as well as core funding from Cancer Research UK, the UK Medical Research Council and the British Heart Foundation to the Oxford University Clinical Trial Service Unit (grant MC_U137686858) and Department of Health, UK (091/0203).

Publisher Copyright:
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC

Keywords

  • breast cancer
  • heart disease
  • radiotherapy

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