High Estrogen Receptor β Expression Is Prognostic among Adjuvant Chemotherapy-Treated Patients-Results from a Population-Based Breast Cancer Cohort.
OBJECTIVE
Isoform-specific tumor estrogen receptor β (ERβ) expression may hold prognostic information in breast cancer, especially among endocrine-treated breast cancer patients. The study's purpose was to evaluate ERβ isoform 1 (ERβ1) expression in relation to tumor characteristics, ESR2 genotypes, and prognosis in different treatment groups.


METHODS
A population-based prospective cohort of 1,026 patients diagnosed with primary invasive breast cancer in Lund, Sweden, between October 2002 and June 2012 was followed until June 2014 (median 5 years). Associations between immunohistochemical ERβ1 expression, patient and tumor characteristics, as well as outcome within treatment groups were analyzed.


RESULTS
Tumor ERβ1 expression was available for 911 patients (89%) and was not associated with ESR2 genotypes. ERβ1 positivity, defined as >75% (ERβ175+, 72.7%), was positively associated with established favorable tumor characteristics. Overall, ERβ175+was associated with lower risk of breast cancer events [HRadj= 0.60; 95% confidence interval (CI), 0.41-0.89]. The magnitude of the association was larger in patients with ERα-tumors (HRadj= 0.30; 95% CI, 0.12-0.76), compared with ERα+tumors (HRadj= 0.66; 95% CI, 0.42-1.03). Among the 232 chemotherapy-treated patients, ERβ175+tumors were associated with lower risk of breast cancer events compared with ERβ175-tumors (HRadj= 0.31; 95% CI, 0.15-0.64). Among the 671 chemonaïve patients, ERβ175status was not associated with the outcome.


CONCLUSIONS
High ERβ1 expression was a favorable prognostic marker in this breast cancer cohort, especially in chemotherapy-treated patients, but not in endocrine therapy-treated patients. These results warrant confirmation, preferably via a biomarker study in a previously conducted randomized trial. Clin Cancer Res; 23(3); 766-77. ©2016 AACR.
Department of Clinical Sciences Lund, Division of Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden.|Department of Plastic and Reconstructive Surgery, Skåne University Hospital, Sweden.
Karin
K
Elebro
Department of Clinical Sciences Lund, Division of Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden.|Department of Oncology and Hematology, Skåne University Hospital, Sweden.
Signe
S
Borgquist
Department of Clinical Sciences Lund, Division of Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden.
Ann H
AH
Rosendahl
Department of Clinical Sciences Lund, Division of Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden.
Andrea
A
Markkula
Department of Clinical Sciences Lund, Division of Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden.
Maria
M
Simonsson
Department of Clinical Sciences Lund, Division of Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden.
Karin
K
Jirström
CREATE Health and Department of Immunotechnology, Faculty of Engineering, Lund University, Lund, Sweden.
Carsten
C
Rose
Department of Clinical Sciences Lund, Surgery, Faculty of Medicine, Lund University, and Skåne University Hospital, Sweden.
Christian
C
Ingvar
Department of Clinical Sciences Lund, Division of Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden. helena.jernstrom@med.lu.se.
Helena
H
Jernström
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D047629:Estrogen Receptor beta / Q000032:analysis* / Q000235:genetics; D004967:Estrogens; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008408:Mastectomy; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000188:drug therapy* / Q000601:surgery; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D020033:Protein Isoforms / Q000032:analysis; D046888:Tissue Array Analysis; D000068878:Trastuzumab / Q000627:therapeutic use; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; C000600034:ESR2 protein, human; D047629:Estrogen Receptor beta; D004967:Estrogens; D020033:Protein Isoforms; D000068878:Trastuzumab