title: Identification of a Low-Risk Luminal A Breast Cancer Cohort That May Not Benefit From Breast Radiotherapy.
abstract: OBJECTIVE
  To determine the prognostic and predictive value of intrinsic subtyping by using immunohistochemical (IHC) biomarkers for ipsilateral breast relapse (IBR) in participants in an early breast cancer randomized trial of tamoxifen with or without breast radiotherapy (RT).
  
  
  METHODS
  IHC analysis of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6, epidermal growth factor receptor, and Ki-67 was conducted on 501 of 769 available blocks. Patients were classified as luminal A (n = 265), luminal B (n = 165), or high-risk subtype (luminal HER2, n = 22; HER2 enriched, n = 13; basal like, n = 30; or triple-negative nonbasal, n = 6). Median follow-up was 10 years.
  
  
  RESULTS
  Classification by subtype was prognostic for IBR (10-year estimates: luminal A, 5.2%; luminal B, 10.5%; high-risk subtypes, 21.3%; P < .001). Luminal subtypes seemed to derive less benefit from RT (luminal A hazard ratio [HR], 0.40; luminal B HR, 0.51) than high-risk subtypes (HR, 0.13); however, the overall subtype-treatment interaction term was not significant (P = .26). In an exploratory analysis of women with clinical low-risk (age older than 60 years, T1, grade 1 or 2) luminal A tumors (n = 151), 10-year IBR was 3.1% versus 11.8% for the high-risk cohort (n = 341; P = .0063). Clinical low-risk luminal A patients had a 10-year IBR of 1.3% with tamoxifen versus 5.0% with tamoxifen plus RT (P = .42). Multivariable analysis showed that RT (HR, 0.31; P < .001), clinical risk group (HR, 2.2; P = .025), and luminal A subtype (HR, 0.25; P < .001) were significantly associated with IBR.
  
  
  CONCLUSIONS
  IHC subtyping was prognostic for IBR but was not predictive of benefit from RT. Further studies may validate the exploratory finding of a low-risk luminal A group who may be spared breast RT.
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Done
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: Naomi
authors.initials: N
authors.lastname: Miller
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Voduc
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: Sharon
authors.initials: S
authors.lastname: Nofech-Mozes
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Whelan
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: Lorna M
authors.initials: LM
authors.lastname: Weir
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: Ivo A
authors.initials: IA
authors.lastname: Olivotto
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada.
authors.forename: David R
authors.initials: DR
authors.lastname: McCready
authors.affiliation: Fei-Fei Liu, Anthony W. Fyles, Wei Shi, Susan J. Done, Naomi Miller, Melania Pintilie, and David R. McCready, Princess Margaret Cancer Centre/University Health Network; Sharon Nofech-Mozes, Sunnybrook Odette Cancer Center; Martin C. Chang, Mt. Sinai Hospital, University of Toronto, Toronto; Timothy J. Whelan, Juravinski Cancer Centre, McMaster University, Hamilton, ON; David Voduc, Torsten O. Nielsen, and Lorna M. Weir, British Columbia Cancer Agency, Vancouver; and Ivo A. Olivotto, British Columbia Cancer Agency, Victoria, BC, Canada. anthony.fyles@rmp.uhn.on.ca.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Fyles
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D066246:ErbB Receptors / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053555:Keratin-5 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D047628:Estrogen Receptor alpha; D053555:Keratin-5; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C506487:ESR1 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human