title: Tumor factors predictive of response to hypofractionated radiotherapy in a randomized trial following breast conserving therapy.
abstract: OBJECTIVE
  To determine whether tumor grade, molecular subtype and hypoxia predict response to hypofractionated versus standard radiotherapy (RT) following breast-conserving surgery (BCS) for node-negative breast cancer in a randomized controlled trial (RCT).
  
  
  METHODS
  Formalin-fixed paraffin-embedded (FFPE) tumor blocks were available on 989 of 1234 patients enrolled in the Hypofractionation Whole Breast Irradiation (HWBI) Trial. A central pathology review and assessment of tumor grade using the Nottingham grading system was carried out. Tumors were classified by molecular subtype as luminal A, luminal B, HER2 enriched, basal-like or unclassified using a six-biomarker panel; ER, PR, HER-2, Ki67, CK5/6 and EGFR. Tumors were also classified as hypoxic based on the expression of HIF1α, CAIX or GLUT-1. The primary end point was local recurrence (LR).
  
  
  RESULTS
  Median follow-up was 12 years. In the multivariable Cox model, molecular subtype was the only factor predictive of LR, the 10-year cumulative incidence was 4.5% for luminal A and basal-like, 7.9% for luminal B and 16.9% for HER-2 enriched tumors (P < 0.01). Tumor grade, molecular subtype or hypoxia did not predict response to hypofractionation.
  
  
  CONCLUSIONS
  In women enrolled in the HWBI trial following BCS tumor molecular subtype predicted LR. However tumor grade, molecular subtype and hypoxia did not predict response to hypofractionation suggesting that patients with node-negative breast tumors of all grades and molecular subtypes may be safely treated with hypofractionated RT regimens.
authors.affiliation: Department of Pathology and Molecular Medicine.
authors.forename: A L
authors.initials: AL
authors.lastname: Bane
authors.forename: T J
authors.initials: TJ
authors.lastname: Whelan
authors.forename: G R
authors.initials: GR
authors.lastname: Pond
authors.forename: S
authors.initials: S
authors.lastname: Parpia
authors.forename: G
authors.initials: G
authors.lastname: Gohla
authors.forename: A W
authors.initials: AW
authors.lastname: Fyles
authors.forename: J-P
authors.initials: JP
authors.lastname: Pignol
authors.forename: K I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: S
authors.initials: S
authors.lastname: Chambers
authors.forename: M N
authors.initials: MN
authors.lastname: Levine
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D015687:Cell Hypoxia; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000517:prevention & control; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: biomarker; breast cancer; hypofractionated radiotherapy; randomized controlled trial