Fei-Fei Liu1, Wei Shi1, Susan J Done1, Naomi Miller1, Melania Pintilie1, David Voduc1, Torsten O Nielsen1, Sharon Nofech-Mozes1, Martin C Chang1, Timothy J Whelan1, Lorna M Weir1, Ivo A Olivotto1, David R McCready1, Anthony W Fyles2. 1. 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. 2. 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.
Abstract
PURPOSE: 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 oftamoxifen with or without breast radiotherapy (RT). PATIENTS AND 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. CONCLUSION: 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.
RCT Entities:
PURPOSE: 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). PATIENTS AND 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. CONCLUSION: 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.
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