title: Second malignancies after adjuvant radiation therapy for early stage breast cancer: is there increased risk with addition of regional radiation to local radiation?
abstract: OBJECTIVE
  This study was undertaken to determine whether there was an increased risk of second malignancies (SM), particularly lung cancer, in early stage breast cancer patients treated with the addition of nodal fields to breast and/or chest wall radiation therapy (RT).
  
  
  METHODS
  Subjects were stage I/II female breast cancer patients 20 to 79 years of age, diagnosed between 1989 and 2005 and treated with adjuvant RT at our institution. Patients were included if they survived and did not have SM within 3 years of diagnosis. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to compare SM incidence to cancer incidence in the general sex- and age-matched populations. Secondary malignancy risks in patients treated with local RT (LRT) to the breast/chest wall were compared to those in patients treated with locoregional RT (LRRT) to the breast/chest wall and regional nodes, using multivariate regression analysis (MVA) to account for covariates.
  
  
  RESULTS
  The cohort included 12,836 patients with a median follow-up of 8.4 years. LRRT was used in 18% of patients. The SIR comparing patients treated with LRT to the general population was 1.29 (CI: 1.21-1.38). No statistically significant increased incidence of in-field malignancies (SIR, 1.04; CI: 0.87-1.23) and lung cancers (SIR, 1.06; CI: 0.88-1.26) was detected. The SIR comparing patients treated with LRRT to the general population was 1.39 (CI: 1.17-1.64). No statistically significant increased incidence of in-field malignancies (SIR, 1.26; CI: 0.77-1.94) and lung cancers (SIR, 1.27; CI: 0.76-1.98) was detected. On MVA comparing LRRT to LRT, the adjusted hazard ratio was 1.20 for in-field malignancies (CI: 0.68-2.16) and 1.26 for lung cancer (CI: 0.67-2.36). The excess attributable risk (EAR) to regional RT was 3.1 per 10,000 person years (CI: -8.7 to 9.9).
  
  
  CONCLUSIONS
  No statistically significant increased risk of second malignancy was detected after LRRT relative to that for LRT. The upper limit of the EAR was approximately 1% at 10 years.
authors.affiliation: Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Radiation Oncology, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada.
authors.forename: Sarah Nicole
authors.initials: SN
authors.lastname: Hamilton
authors.affiliation: Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Radiation Oncology, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada. Electronic address: styldesl@bccancer.bc.ca.
authors.forename: Scott
authors.initials: S
authors.lastname: Tyldesley
authors.affiliation: Cancer Control Research Department, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, British Columbia Cancer Agency-Centre for the North, Prince George, British Columbia, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Olson
authors.affiliation: Cancer Control Research Department, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: McBride
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D001955:British Columbia; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology*; D015182:Lymphatic Irradiation / Q000009:adverse effects; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000209:etiology*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D012044:Regression Analysis; D035441:Thoracic Wall / Q000528:radiation effects; D047368:Tumor Burden; D055815:Young Adult