L M Morton1, E S Gilbert2, P Hall3, M Andersson4, H Joensuu5, L Vaalavirta5, G M Dores6, M Stovall7, E J Holowaty8, C F Lynch9, R E Curtis2, S A Smith7, R A Kleinerman2, M Kaijser10, H H Storm11, E Pukkala12, R E Weathers7, M S Linet2, P Rajaraman2, J F Fraumeni2, L M Brown13, F E van Leeuwen14, S D Fossa15, T B Johannesen16, F Langmark16, S Lamart2, L B Travis17, B M P Aleman18. 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA. Electronic address: mortonli@mail.nih.gov. 2. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA. 3. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. 4. Department of Oncology, Copenhagen University Hospital, Copenhagen, Denmark. 5. Department of Oncology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland. 6. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA; US Department of Veterans Affairs Medical Center, Oklahoma City. 7. Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, USA. 8. Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. 9. Department of Epidemiology, University of Iowa, Iowa City, USA. 10. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden. 11. Cancer Prevention and Documentation, Danish Cancer Society, Copenhagen, Denmark. 12. Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland. 13. Statistics & Epidemiology, RTI International, Rockville, USA. 14. Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 15. Department of Oncology, Oslo University Hospital and University of Oslo, Oslo, Norway. 16. Cancer Registry of Norway, Oslo, Norway. 17. Department of Radiation Oncology, University of Rochester Medical Center, Rochester, USA. 18. Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abstract
BACKGROUND: Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use. DESIGN: Nested case-control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records. RESULTS: The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P(trend )< 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7-28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2-0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking). CONCLUSIONS: Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.
BACKGROUND: Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use. DESIGN: Nested case-control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records. RESULTS: The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P(trend )< 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7-28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2-0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking). CONCLUSIONS:Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.
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