title: Breast cancer in female survivors of Wilms tumor: a report from the national Wilms tumor late effects study.
abstract: BACKGROUND
  The standard treatment of pulmonary metastases in patients with Wilms tumor (WT) includes 12-gray radiotherapy (RT) to the entire chest. To the authors' knowledge, the risk of breast cancer (BC) in a large cohort of female survivors of WT has not previously been reported.
  
  
  METHODS
  A total of 2492 female participants in National Wilms Tumor Studies 1 through 4 (1969-1995) were followed from age 15 years through the middle of 2013 for incident BC. The median age at the time of last contact was 27.3 years. The authors calculated cumulative risk at age 40 years (CR40), hazard ratios (HR) by Cox regression, standardized incidence ratios (SIRs) relative to US population rates, and 95% confidence intervals (95% CIs).
  
  
  RESULTS
  The numbers of survivors with invasive BC divided by the numbers at risk were 16 of 369 (CR40, 14.8% [95% CI, 8.7-24.5]) for women who received chest RT for metastatic WT, 10 of 894 (CR40, 3.1% [95% CI, 1.3-7.41]) for those who received only abdominal RT, and 2 of 1229 (CR40, 0.3% [95% CI, 0.0-2.3]) for those who received no RT. The SIRs for these 3 groups were 27.6 (95% CI, 16.1-44.2) based on 5010 person-years (PY) of follow-up, 6.0 (95% CI, 2.9-11.0) based on 13,185 PY of follow-up, and 2.2 (95% CI, 0.3-7.8) based on 13,560 PY of follow-up, respectively. The risk was high regardless of the use of chest RT among women diagnosed with WT at age ≥10 years, with 9 of 90 women developing BC (CR40, 13.5% [95% CI, 5.6-30.6]; SIR, 23.6 [95% CI, 10.8-44.8] [PY, 1463]).
  
  
  CONCLUSIONS
  Female survivors of WT who were treated with chest RT had a high risk of developing early BC, with nearly 15% developing invasive disease by age 40 years. Current guidelines that recommend screening only those survivors who received ≥20 Gy of RT to the chest might be reevaluated.
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Lange
authors.forename: Janice R
authors.initials: JR
authors.lastname: Takashima
authors.forename: Susan M
authors.initials: SM
authors.lastname: Peterson
authors.forename: John A
authors.initials: JA
authors.lastname: Kalapurakal
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Green
authors.forename: Norman E
authors.initials: NE
authors.lastname: Breslow
mesh_terms: D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000453:epidemiology*; D002170:Canada / Q000453:epidemiology; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology*; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000628:therapy; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000532:radiotherapy / Q000556:secondary; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology*; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012307:Risk Factors; D014481:United States; D009396:Wilms Tumor / Q000453:epidemiology* / Q000473:pathology / Q000628:therapy; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
keywords: Wilms tumor; cancer survivorship; doxorubicin; radiotherapy; secondary malignant neoplasms