PURPOSE: We examined borderline estrogen receptor (ER) -positive cancers, defined as having 1% to 10% positivity by immunohistochemistry (IHC), to determine whether they show the same global gene-expression pattern and high ESR1 mRNA expression as ER-positive cancers or if they are more similar to ER-negative cancers. PATIENTS AND METHODS: ER status was determined by IHC in 465 primary breast cancers and with the Affymetrix U133A gene chip. We compared expressions of ESR1 mRNA and a 106 probe set ER-associated gene signature score between ER-negative (n = 183), 1% to 9% (n = 25), 10% (n = 6), and more than 10% (n = 251) ER-positive cancers. We also assessed the molecular class by using the PAM50 classifier and plotted survival by ER status. RESULTS: Among the 1% to 9%, 10%, and more than 10% ER IHC-positive patients, 24%, 67%, and 92% were also positive by ESR1 mRNA expression. The average ESR1 expression was significantly higher in the ≥ 10% ER-positive cohorts compared with the 1% to 9% or ER-negative cohort. The average ER gene signature scores were similar for the ER-negative and 1% to 9% IHC-positive patients and were significantly lower than in ≥ 10% ER-positive patients. Among the 1% to 9% ER-positive patients, 8% were luminal B and 48% were basal-like; among the 10% ER-positive patients, 50% were luminal. The overall survival rate of 1% to 9% ER-positive patients with cancer was between those of patients in the ≥ 10% ER-positive and ER-negative groups. CONCLUSION: A minority of the 1% to 9% IHC ER-positive tumors show molecular features similar to those of ER-positive, potentially endocrine-sensitive tumors, whereas most show ER-negative, basal-like molecular characteristics. The safest clinical approach may be to use both adjuvant endocrine therapy and chemotherapy in this rare subset of patients.
PURPOSE: We examined borderline estrogen receptor (ER) -positive cancers, defined as having 1% to 10% positivity by immunohistochemistry (IHC), to determine whether they show the same global gene-expression pattern and high ESR1 mRNA expression as ER-positive cancers or if they are more similar to ER-negative cancers. PATIENTS AND METHODS: ER status was determined by IHC in 465 primary breast cancers and with the Affymetrix U133A gene chip. We compared expressions of ESR1 mRNA and a 106 probe set ER-associated gene signature score between ER-negative (n = 183), 1% to 9% (n = 25), 10% (n = 6), and more than 10% (n = 251) ER-positive cancers. We also assessed the molecular class by using the PAM50 classifier and plotted survival by ER status. RESULTS: Among the 1% to 9%, 10%, and more than 10% ER IHC-positive patients, 24%, 67%, and 92% were also positive by ESR1 mRNA expression. The average ESR1 expression was significantly higher in the ≥ 10% ER-positive cohorts compared with the 1% to 9% or ER-negative cohort. The average ER gene signature scores were similar for the ER-negative and 1% to 9% IHC-positive patients and were significantly lower than in ≥ 10% ER-positive patients. Among the 1% to 9% ER-positive patients, 8% were luminal B and 48% were basal-like; among the 10% ER-positive patients, 50% were luminal. The overall survival rate of 1% to 9% ER-positive patients with cancer was between those of patients in the ≥ 10% ER-positive and ER-negative groups. CONCLUSION: A minority of the 1% to 9% IHC ER-positive tumors show molecular features similar to those of ER-positive, potentially endocrine-sensitive tumors, whereas most show ER-negative, basal-like molecular characteristics. The safest clinical approach may be to use both adjuvant endocrine therapy and chemotherapy in this rare subset of patients.
Authors: Maggie C U Cheang; Miguel Martin; Torsten O Nielsen; Aleix Prat; David Voduc; Alvaro Rodriguez-Lescure; Amparo Ruiz; Stephen Chia; Lois Shepherd; Manuel Ruiz-Borrego; Lourdes Calvo; Emilio Alba; Eva Carrasco; Rosalia Caballero; Dongsheng Tu; Kathleen I Pritchard; Mark N Levine; Vivien H Bramwell; Joel Parker; Philip S Bernard; Matthew J Ellis; Charles M Perou; Angelo Di Leo; Lisa A Carey Journal: Oncologist Date: 2015-04-23
Authors: Meenakshi Anurag; Nindo Punturi; Jeremy Hoog; Matthew N Bainbridge; Matthew J Ellis; Svasti Haricharan Journal: Clin Cancer Res Date: 2018-05-23 Impact factor: 12.531
Authors: M Yi; L Huo; K B Koenig; E A Mittendorf; F Meric-Bernstam; H M Kuerer; I Bedrosian; A U Buzdar; W F Symmans; J R Crow; M Bender; R R Shah; G N Hortobagyi; K K Hunt Journal: Ann Oncol Date: 2014-02-20 Impact factor: 32.976
Authors: Katherine C Kurnit; Ecaterina E Ileana Dumbrava; Beate Litzenburger; Yekaterina B Khotskaya; Amber M Johnson; Timothy A Yap; Jordi Rodon; Jia Zeng; Md Abu Shufean; Ann M Bailey; Nora S Sánchez; Vijaykumar Holla; John Mendelsohn; Kenna Mills Shaw; Elmer V Bernstam; Gordon B Mills; Funda Meric-Bernstam Journal: Clin Cancer Res Date: 2018-02-02 Impact factor: 12.531