title: Histologic subtypes of breast cancer following radiotherapy for Hodgkin lymphoma.
abstract: BACKGROUND
  The purpose of the study was to determine whether breast cancers (BCs) that develop in women previously irradiated for Hodgkin lymphoma (HL) are biologically similar to sporadic BC.
  
  
  METHODS
  We retrospectively reviewed the charts of patients who developed BC after radiotherapy (RT) for HL. Tumors were classified as ductal carcinoma in situ (DCIS) or invasive carcinoma. Invasive carcinomas were further characterized according to the subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. BCs after HL were compared with four age-matched sporadic, non-breast cancer (BRCA) I or II mutated BCs.
  
  
  RESULTS
  One hundred forty-seven HL patients who were treated with RT between 1966 and 1999 and subsequently developed BCs were identified. Of these, 65 patients with 71 BCs had complete pathologic information. The median age at HL diagnosis was 23 (range, 10-48). The median age at BC diagnosis was 44 (range, 28-66). The median time to developing BC was 20 years. Twenty cancers (28%) were DCIS and 51 (72%) were invasive. Of the 51 invasive cancers, 24 (47%) were HR+/HER2-, 2 (4%) were HR+/HER2+, 5 (10%) were HR-/HER2+, and 20 (39%) were HR-/HER2-. There were no differences in BC histologic subtype according to the age at which patients were exposed to RT, the use of chemotherapy for HL treatment, or the time from RT exposure to the development of BC. In a 4 : 1 age-matched comparison to sporadic BCs, BCs after HL were more likely to be HR-/HER2- (39% versus 14%) and less likely to be HR+/HER2- (47% versus 61%) or HR+/HER2+ (4% versus 14%) (P = 0.0003).
  
  
  CONCLUSIONS
  BCs arising in previously irradiated breast tissue were more likely to be triple negative compared with age-matched sporadic invasive cancers and less likely to be HR positive. Further studies will be important to determine the molecular pathways of carcinogenesis in breast tissue that is exposed to RT.
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford. Electronic address: kateh@stanford.edu.
authors.forename: K C
authors.initials: KC
authors.lastname: Horst
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford.
authors.forename: S L
authors.initials: SL
authors.lastname: Hancock
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford.
authors.forename: G
authors.initials: G
authors.lastname: Ognibene
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford.
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Medicine, Division of Medical Oncology, Stanford University School of Medicine, Stanford, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Advani
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford; Department of Medicine, Division of Medical Oncology, Stanford University School of Medicine, Stanford, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Rosenberg
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford.
authors.forename: S S
authors.initials: SS
authors.lastname: Donaldson
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford.
authors.forename: R T
authors.initials: RT
authors.lastname: Hoppe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000145:classification / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D002648:Child; D005260:Female; D006689:Hodgkin Disease / Q000150:complications / Q000532:radiotherapy*; D006801:Humans; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Hodgkin lymphoma; breast cancer; breast cancer subtype; chest radiotherapy