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Cited by 1,049Breast Cancer Treatment StudiesEffects of Radiation ExposureMultiple and Secondary Primary Cancers

Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: Prospective cohort study of about 300,000 women in us seer cancer registries

Darby, Sarah C, McGale, Paul, Taylor, Carolyn W, Peto, Richard·2005·The Lancet Oncology
DOI 10.1016/s1470-2045(05)70251-5
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Abstract

Background Radiotherapy for early breast cancer can decrease breast cancer mortality but increase other mortality, mainly from heart disease and lung cancer. The mean cardiac dose from irradiation of a left-sided breast cancer can be two or three times that for a right-sided breast cancer. The mean ipsilateral (ie, on the same side as the breast cancer) lung dose can also be two or three times the mean contralateral lung dose. Particularly during the 1970s, when typical heart and lung exposures were greater than now, the laterality of an irradiated breast cancer could measurably affect cardiac mortality and mortality from cancer of the right or the left lung decades later. This study aimed to assess the hazards in the general US population from routine cancer-registry and death-certificate data.Methods We analysed data for 308 861 US women with early breast cancer of known laterality (left-sided or right-sided) who were registered in the US Surveillance Epidemiology and End Results (SEER) cancer registries during 1973-2001 and followed prospectively for cause-specific mortality until Jan 1, 2002.Findings 115 165 (37%) received radiotherapy. Among those who did not, tumour laterality was of little relevance to subsequent mortality. For women diagnosed during 1973-82 and irradiated, the cardiac mortality ratio (left versus right tumour laterality) was 1.20 (95% CI 1.04-1.38) less than 10 years afterwards, 1.42 (1.11-1.82) 10-14 years afterwards, and 1.58 (1.29-1.95) after 15 years or more (trend: 2p=0.03). For women diagnosed during 1983-92 and irradiated, the cardiac mortality ratio was 1.04 (0.91-1.18) less than 10 years afterwards and 1.27 (0.99-1.63) 10 or more years afterwards. For women diagnosed during 1993-2001 and irradiated the cardiac mortality ratio was 0.96 (0.82-1.12), with none yet followed for 10 years. Among women irradiated for breast cancer who subsequently developed an ipsilateral or contralateral lung cancer, the lung cancer mortality ratio (ipsilateral versus contralateral) for women diagnosed during 1973-82 and irradiated was 1.17 (0.62-2.19), 2.00 (1.00-4.00), and 2.71 (1.65-4.48), respectively, less than 10 years, 10-14 years, and 15 or more years afterwards (trend: 2p=0.04). For women irradiated after 1982 there is, as yet, little information on lung cancer risks more than 10 years afterwards.Interpretation US breast cancer radiotherapy regimens of the 1970s and early 1980s appreciably increased mortality from heart disease and lung cancer 10-20 years afterwards with, as yet, little direct evidence on the hazards after more than 20 years. Since the early 1980s, improvements in radiotherapy planning should have reduced such risks, but the long-term hazards in the general populations of various countries still need to be monitored directly.

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  • Epidemiological studies on atomic bomb survivors, radiotherapy patients and occupationally-exposed workers have characterized the association between moderate to high doses of low-LET radiation and the long-term development of degenerative tissue effects, such as heart disease, cataracts, immunological changes and premature aging.

    “Epidemiological studies on atomic bomb survivors in Japan, radiotherapy patients and occupationally-exposed workers have characterized the association between moderate to high doses of low-LET radiation and the long-term development of degenerative tissue effects, such as heart disease, cataracts, immunological changes and premature aging [17,18,19,20].”

    From Space Radiation: The number one risk to astronaut health beyond low earth orbit (2014) · cites this paper as [17]

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Authors
Darby, S. C., McGale, P., Taylor, C. W., & Peto, R.
Affiliations
University of Oxford (GB)
Corresponding author
Darby, Sarah C
ORCID
Venue
The Lancet Oncology
Publisher
Elsevier BV
Published
2005-08
Volume
6
Issue
8
Pages
557-565
ISSN
1470-2045 (ISSN-L)
DOI
10.1016/s1470-2045(05)70251-5
OpenAlex
W2140492419
Cited by
1,049
References
33
Citations by year
2026: 21 · 2025: 40 · 2024: 40 · 2023: 39 · 2022: 63 · 2021: 68 · 2020: 66 · 2019: 56 · 2018: 71 · 2017: 58 · 2016: 75 · 2015: 60 · 2014: 49 · 2013: 68 · 2012: 54
FWCI
9.69
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • The Lancet Oncology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Cancer Research UK
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
Keywords
early breast cancer, radiotherapy, cardiac mortality, lung cancer mortality, left-sided breast cancer, radiation-induced heart disease, radiation-induced lung cancer, long-term mortality, breast-conserving therapy, SEER database, women's health, cancer survivorship, cause-specific mortality, late radiation effects
MeSH terms
Adult, Aged, Breast Neoplasms, Female, Follow-Up Studies, Heart Diseases, Humans, Functional Laterality, Lung Neoplasms, Middle Aged, Radiation Injuries, SEER Program

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