Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials

Purpose Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage points in suitable women but can cause a second cancer or heart disease decades later. We estimated the absolute long-term risks of modern breast cancer radiotherapy. Methods First, a systematic literature review was performed of lung and heart doses in breast cancer regimens published during 2010 to 2015. Second, individual patient data meta-analyses of 40,781 women randomly assigned to breast cancer radiotherapy versus no radiotherapy in 75 trials yielded rate ratios (RRs) for second primary cancers and cause-specific mortality and excess RRs (ERRs) per Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied to current smoker and nonsmoker lung cancer and cardiac mortality rates in population-based data. Results Average doses from 647 regimens published during 2010 to 2015 were 5.7 Gy for whole lung and 4.4 Gy for whole heart. The median year of irradiation was 2010 (interquartile range [IQR], 2008 to 2011). Meta-analyses yielded lung cancer incidence ≥ 10 years after radiotherapy RR of 2.10 (95% CI, 1.48 to 2.98; P < .001) on the basis of 134 cancers, indicating 0.11 (95% CI, 0.05 to 0.20) ERR per Gy whole-lung dose. For cardiac mortality, RR was 1.30 (95% CI, 1.15 to 1.46; P < .001) on the basis of 1,253 cardiac deaths. Detailed analyses indicated 0.04 (95% CI, 0.02 to 0.06) ERR per Gy whole-heart dose. Estimated absolute risks from modern radiotherapy were as follows: lung cancer, approximately 4% for long-term continuing smokers and 0.3% for nonsmokers; and cardiac mortality, approximately 1% for smokers and 0.3% for nonsmokers. Conclusion For long-term smokers, the absolute risks of modern radiotherapy may outweigh the benefits, yet for most nonsmokers (and ex-smokers), the benefits of radiotherapy far outweigh the risks. Hence, smoking can determine the net effect of radiotherapy on mortality, but smoking cessation substantially reduces radiotherapy risk.

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Risk of primary lung cancer after breast cancer radiotherapy: A systematic review and meta-analysis

10.21203/rs.3.rs-419176/v1 ◽

2021 ◽

Author(s):

Bushra Zareie ◽

Mohammad Aziz Rasouli ◽

Jalal Poorolajal

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Meta Analysis ◽

Primary Lung Cancer ◽

Epidemiological Studies ◽

Cancer Radiotherapy ◽

Breast Cancer Radiotherapy ◽

Newcastle Ottawa Scale ◽

Study Participants

Abstract Background: Epidemiological studies have shown that the risk of secondary malignancies may increase by radiotherapy. Lung cancer is the most important long-term complication of breast cancer radiotherapy.Methods: Major electronic databases including Scopus, Web of Science, and MEDLINE were searched. All cohort studies that investigated the association between radiotherapy for breast cancer and risk of primary lung, bronchus and trachea cancers conducted until March 2021 were included. The study participants were evaluated regardless of their age and ethnicity. The Newcastle-Ottawa Scale was used to assess the quality of the studies. The designated effects were risk ratio (RR). The random-effects model was used to estimate the average effects.Results: Fifteen studies including 1,640,247 women with primary breast cancer were identified of which 937,151 had not received radiotherapy and 703,096 subjects had received radiotherapy. In general, there was no significant association between breast cancer radiotherapy and lung cancer based on 10 studies (RR=0.95, 95%CI: 0.87-1.02, P=0.15), There was no association between breast cancer radiotherapy and lung, bronchus, and trachea cancers either based on 5 studies (RR=0.98, 95%CI: 0.93-1.02, P=0.32).Conclusion: Radiotherapy for breast cancer is not associated with an excess risk of lung cancer. Due to the limited number of studies, further research about lung doses from breast cancer radiotherapy varied substantially worldwide, is suggested to the risk of lung cancer after breast cancer radiotherapy.

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Risk of primary lung cancer after breast cancer radiotherapy: A systematic review and meta-analysis

10.21203/rs.3.rs-419176/v2 ◽

2021 ◽

Author(s):

Bushra Zareie ◽

Mohammad Aziz Rasouli ◽

Jalal Poorolajal

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Meta Analysis ◽

Primary Lung Cancer ◽

Epidemiological Studies ◽

Cancer Radiotherapy ◽

Breast Cancer Radiotherapy ◽

Newcastle Ottawa Scale ◽

Study Participants

Abstract Background: Epidemiological studies have shown that the risk of secondary malignancies may increase by radiotherapy. Lung cancer is the most important long-term complication of breast cancer radiotherapy.Methods: Major electronic databases including Scopus, Web of Science, and MEDLINE were searched. All cohort studies that investigated the association between radiotherapy for breast cancer and risk of primary lung, bronchus and trachea cancers conducted until March 2021 were included. The study participants were evaluated regardless of their age and ethnicity. The Newcastle-Ottawa Scale was used to assess the quality of the studies. The designated effects were risk ratio (RR). The random-effects model was used to estimate the average effects.Results: Fifteen studies including 1,640,247 women with primary breast cancer were identified of which 937,151 had not received radiotherapy and 703,096 subjects had received radiotherapy. In general, there was no significant association between breast cancer radiotherapy and lung cancer based on 10 studies (RR=0.95, 95% CI: 0.87-1.02, P=0.15), There was no association between breast cancer radiotherapy and lung, bronchus, and trachea cancers either based on 5 studies (RR=0.98, 95% CI: 0.93-1.02, P=0.32).Conclusion: Radiotherapy for breast cancer is not associated with an excess risk of lung cancer. Due to the limited number of studies, further research about lung doses from breast cancer radiotherapy varied substantially worldwide, is suggested to the risk of lung cancer after breast cancer radiotherapy.

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LONG-TERM HEALTH RISK AFTER BREAST-CANCER RADIOTHERAPY: OVERVIEW OF PASSOS METHODOLOGY AND SOFTWARE

Radiation Protection Dosimetry ◽

10.1093/rpd/ncy219 ◽

2018 ◽

Vol 183 (1-2) ◽

pp. 259-263 ◽

Cited By ~ 6

Author(s):

Markus Eidemüller ◽

Cristoforo Simonetto ◽

Pavel Kundrát ◽

Alexander Ulanowski ◽

Elena Shemiakina ◽

...

Keyword(s):

Breast Cancer ◽

Health Risk ◽

Cancer Radiotherapy ◽

Breast Cancer Radiotherapy

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WHAT ANATOMIC FEATURES GOVERN PERSONAL LONG-TERM HEALTH RISKS FROM BREAST CANCER RADIOTHERAPY?

Radiation Protection Dosimetry ◽

10.1093/rpd/ncz236 ◽

2019 ◽

Vol 186 (2-3) ◽

pp. 381-385

Author(s):

Pavel Kundrát ◽

Cristoforo Simonetto ◽

Markus Eidemüller ◽

Julia Remmele ◽

Hannes Rennau ◽

...

Keyword(s):

Breast Cancer ◽

Health Risks ◽

Individual Risk ◽

Breast Cancer Patients ◽

Cancer Radiotherapy ◽

Breast Cancer Radiotherapy ◽

Radiation Induced ◽

Risk Variability ◽

The Individual

Abstract Breast cancer radiotherapy may in the long term lead to radiation-induced secondary cancer or heart disease. These health risks hugely vary among patients, partially due to anatomy-driven differences in doses deposited to the heart, ipsilateral lung and contralateral breast. We identify four anatomic features that largely cover these dosimetric variations to enable personalized risk estimates. For three exemplary, very different risk scenarios, the given parameter set reproduces 63–74% of the individual risk variability for left-sided breast cancer patients. These anatomic features will be used in the PASSOS software to support decision processes in breast-cancer therapy.

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Correlation, Causation and Confounding—What Is the True Risk of Lung Cancer following Breast Cancer Radiotherapy?

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2017.02.016 ◽

2017 ◽

Vol 12 (5) ◽

pp. 773-775

Author(s):

Suresh Senan ◽

Alexander V. Louie

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Cancer Radiotherapy ◽

Breast Cancer Radiotherapy

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Estimating the risk of lung cancer and cardiac mortality from doses to the lung and heart from modern tangent-only breast radiotherapy

Journal of Radiotherapy in Practice ◽

10.1017/s1460396918000080 ◽

2018 ◽

Vol 17 (3) ◽

pp. 260-265

Author(s):

Loukas A. Georgiou ◽

Adam F. Farmer

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Heart Disease ◽

Collaborative Group ◽

Cardiac Mortality ◽

Breast Radiotherapy ◽

Heart Dose ◽

Treatment Techniques ◽

The Mean ◽

Whole Heart

AbstractPurposeThe Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) reported that the risks of breast cancer treatment in woman smokers may outweigh the benefits. The data used doses from published reports using a variety of treatment techniques. In our study, the risks of lung cancer and heart disease were determined from a modern era tangential-only technique.Methods and materialsDoses to the lung and heart were obtained for tangential radiotherapy to the breast or chest wall. The risk of lung cancer incidence and cardiac mortality were calculated by taking the ratio of our doses to those published by the EBCTG.ResultsA total of 77 women were identified meeting our inclusion criteria. The mean combined whole lung dose was 2·0 Gy. The mean whole heart dose was 0·9 Gy. The estimated risk of lung cancer and cardiac mortality in a 50-year-old life-long smoker was estimated to be 1·5 and <1%, respectively.ConclusionsTangential only radiotherapy delivered substantially lower doses to the combined whole lung and whole heart than those reported by the EBCTCG. In this cohort, the risks of radiation induced lung cancer and heart disease are outweighed by the benefits of radiotherapy even in those that are smokers.

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Estimating long-term health risks after breast cancer radiotherapy: merging evidence from low and high doses

Radiation and Environmental Biophysics ◽

10.1007/s00411-021-00924-8 ◽

2021 ◽

Author(s):

Cristoforo Simonetto ◽

Daniel Wollschläger ◽

Pavel Kundrát ◽

Alexander Ulanowski ◽

Janine Becker ◽

...

Keyword(s):

Breast Cancer ◽

Health Risks ◽

Dose Response ◽

Heart Diseases ◽

Dose Range ◽

High Dose ◽

Risk Models ◽

Cancer Radiotherapy ◽

Breast Cancer Radiotherapy

AbstractIn breast cancer radiotherapy, substantial radiation exposure of organs other than the treated breast cannot be avoided, potentially inducing second primary cancer or heart disease. While distant organs and large parts of nearby ones receive doses in the mGy–Gy range, small parts of the heart, lung and bone marrow often receive doses as high as 50 Gy. Contemporary treatment planning allows for considerable flexibility in the distribution of this exposure. To optimise treatment with regards to long-term health risks, evidence-based risk estimates are required for the entire broad range of exposures. Here, we thus propose an approach that combines data from medical and epidemiological studies with different exposure conditions. Approximating cancer induction as a local process, we estimate organ cancer risks by integrating organ-specific dose–response relationships over the organ dose distributions. For highly exposed organ parts, specific high-dose risk models based on studies with medical exposure are applied. For organs or their parts receiving relatively low doses, established dose–response models based on radiation-epidemiological data are used. Joining the models in the intermediate dose range leads to a combined, in general non-linear, dose response supported by data over the whole relevant dose range. For heart diseases, a linear model consistent with high- and low-dose studies is presented. The resulting estimates of long-term health risks are largely compatible with rate ratios observed in randomised breast cancer radiotherapy trials. The risk models have been implemented in a software tool PASSOS that estimates long-term risks for individual breast cancer patients.

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