title: Reproductive status at first diagnosis influences risk of radiation-induced second primary contralateral breast cancer in the WECARE study.
abstract: OBJECTIVE
  Our study examined whether reproductive and hormonal factors before, at the time of, or after radiation treatment for a first primary breast cancer modify the risk of radiation-induced second primary breast cancer.
  
  
  METHODS
  The Women's Environmental, Cancer and Radiation Epidemiology (WECARE) Study is a multicenter, population-based study of 708 women (cases) with asynchronous contralateral breast cancer (CBC) and 1399 women (controls) with unilateral breast cancer. Radiotherapy (RT) records, coupled with anthropomorphic phantom simulations, were used to estimate quadrant-specific radiation dose to the contralateral breast for each patient. Rate ratios (RR) and 95% confidence intervals (CI) were computed to assess the relationship between reproductive factors and risk of CBC.
  
  
  RESULTS
  Women who were nulliparous at diagnosis and exposed to ≥1 Gy to the contralateral breast had a greater risk for CBC than did matched unexposed nulliparous women (RR=2.2; 95% CI, 1.2-4.0). No increased risk was seen in RT-exposed parous women (RR=1.1; 95% CI, 0.8-1.4). Women treated with RT who later became pregnant (8 cases and 9 controls) had a greater risk for CBC (RR=6.0; 95% CI, 1.3-28.4) than unexposed women (4 cases and 7 controls) who also became pregnant. The association of radiation with risk of CBC did not vary by number of pregnancies, history of breastfeeding, or menopausal status at the time of first breast cancer diagnosis.
  
  
  CONCLUSIONS
  Nulliparous women treated with RT were at an increased risk for CBC. Although based on small numbers, women who become pregnant after first diagnosis also seem to be at an increased risk for radiation-induced CBC.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. brooksj@mskcc.org
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Brooks
authors.forename: John D
authors.initials: JD
authors.lastname: Boice
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Anne S
authors.initials: AS
authors.lastname: Reiner
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: Lene
authors.initials: L
authors.lastname: Mellemkjær
authors.forename: Julia A
authors.initials: JA
authors.lastname: Knight
authors.forename: Duncan C
authors.initials: DC
authors.lastname: Thomas
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Susan A
authors.initials: SA
authors.lastname: Smith
authors.forename: Marinela
authors.initials: M
authors.lastname: Capanu
authors.forename: Jonine L
authors.initials: JL
authors.lastname: Bernstein
authors.forename: Roy E
authors.initials: RE
authors.lastname: Shore
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001940:Breast / Q000528:radiation effects*; D001942:Breast Feeding; D001943:Breast Neoplasms / Q000209:etiology* / Q000473:pathology / Q000532:radiotherapy*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008593:Menopause / Q000502:physiology; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D010298:Parity; D019047:Phantoms, Imaging; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000209:etiology; D011829:Radiation Dosage; D018570:Risk Assessment; D013997:Time Factors