title: Radiation dose and breast cancer risk in the childhood cancer survivor study.
abstract: OBJECTIVE
  The purpose of this study was to quantify the risk of breast cancer in relation to radiation dose and chemotherapy among survivors of childhood cancer.
  
  
  METHODS
  We conducted a case-control study of breast cancer in a cohort of 6,647 women who were 5-year survivors of childhood cancer and who were treated during 1970 through 1986. One hundred twenty patients with histologically confirmed breast cancer were identified and were individually matched to four selected controls on age at initial cancer and time since initial cancer. Medical physicists estimated radiation dose to the breast tumor site and ovaries on the basis of medical records.
  
  
  RESULTS
  The odds ratio for breast cancer increased linearly with radiation dose, and it reached 11-fold for local breast doses of approximately 40 Gy relative to no radiation (P for trend < .0001). Risk associated with breast irradiation was sharply reduced among women who received 5 Gy or more to the ovaries (P = .002). The excess odds ratio per Gy was 0.36 for those who received ovarian doses less than 5 Gy and was 0.06 for those who received higher doses. Radiation-related risk did not vary significantly by age at exposure. Borderline significantly elevated risks were seen for doxorubicin, dactinomycin, dacarbazine, and carmustine.
  
  
  CONCLUSIONS
  Results confirm the radiation sensitivity of the breast in girls age 10 to 20 years but do not demonstrate a strong effect of age at exposure within this range. Irradiation of the ovaries at doses greater than 5 Gy seems to lessen the carcinogenic effects of breast irradiation, most likely by reducing exposure of radiation-damaged breast cells to stimulating effects of ovarian hormones.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7238, USA. inskippe@mail.nih.gov
authors.forename: Peter D
authors.initials: PD
authors.lastname: Inskip
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Susan A
authors.initials: SA
authors.lastname: Smith
authors.forename: Sue
authors.initials: S
authors.lastname: Hammond
authors.forename: Ann C
authors.initials: AC
authors.lastname: Mertens
authors.forename: John A
authors.initials: JA
authors.lastname: Whitton
authors.forename: Lisa
authors.initials: L
authors.lastname: Diller
authors.forename: Lisa
authors.initials: L
authors.lastname: Kenney
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Donaldson
authors.forename: Anna T
authors.initials: AT
authors.lastname: Meadows
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Neglia
mesh_terms: D000328:Adult; D000367:Age Factors; D001943:Breast Neoplasms / Q000209:etiology*; D016022:Case-Control Studies; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D016017:Odds Ratio; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D017741:Survivors