title: Risk of treatment-related esophageal cancer among breast cancer survivors.
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.
  
  
  METHODS
  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.
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA. Electronic address: mortonli@mail.nih.gov.
authors: L M
authors: LM
authors: Morton
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA.
authors: E S
authors: ES
authors: Gilbert
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors: P
authors: P
authors: Hall
authors: Department of Oncology, Copenhagen University Hospital, Copenhagen, Denmark.
authors: M
authors: M
authors: Andersson
authors: Department of Oncology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
authors: H
authors: H
authors: Joensuu
authors: Department of Oncology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
authors: L
authors: L
authors: Vaalavirta
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA; US Department of Veterans Affairs Medical Center, Oklahoma City.
authors: G M
authors: GM
authors: Dores
authors: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors: M
authors: M
authors: Stovall
authors: Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
authors: E J
authors: EJ
authors: Holowaty
authors: Department of Epidemiology, University of Iowa, Iowa City, USA.
authors: C F
authors: CF
authors: Lynch
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA.
authors: R E
authors: RE
authors: Curtis
authors: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors: S A
authors: SA
authors: Smith
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA.
authors: R A
authors: RA
authors: Kleinerman
authors: Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors: M
authors: M
authors: Kaijser
authors: Cancer Prevention and Documentation, Danish Cancer Society, Copenhagen, Denmark.
authors: H H
authors: HH
authors: Storm
authors: Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.
authors: E
authors: E
authors: Pukkala
authors: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors: R E
authors: RE
authors: Weathers
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA.
authors: M S
authors: MS
authors: Linet
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA.
authors: P
authors: P
authors: Rajaraman
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA.
authors: J F
authors: JF
authors: Fraumeni
authors: Statistics & Epidemiology, RTI International, Rockville, USA.
authors: L M
authors: LM
authors: Brown
authors: Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors: F E
authors: FE
authors: van Leeuwen
authors: Department of Oncology, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors: S D
authors: SD
authors: Fossa
authors: Cancer Registry of Norway, Oslo, Norway.
authors: T B
authors: TB
authors: Johannesen
authors: Cancer Registry of Norway, Oslo, Norway.
authors: F
authors: F
authors: Langmark
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, USA.
authors: S
authors: S
authors: Lamart
authors: Department of Radiation Oncology, University of Rochester Medical Center, Rochester, USA.
authors: L B
authors: LB
authors: Travis
authors: Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors: B M P
authors: BMP
authors: Aleman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000532:radiotherapy; D016022:Case-Control Studies; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000401:mortality*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy / Q000209:etiology* / Q000532:radiotherapy; D016609:Neoplasms, Second Primary / Q000188:drug therapy / Q000209:etiology* / Q000532:radiotherapy; D011879:Radiotherapy Dosage; D012306:Risk; D012307:Risk Factors; D012907:Smoking; D017741:Survivors