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Expression and Role of Epithelial Membrane Proteins in Tumorigenesis of Hormone Receptor-Positive Breast Cancer.

ABSTRACT: Purpose:Studies on the expression of epithelial membrane proteins (EMPs) in breast cancer have been rare and limited. In the present study, we aimed to evaluate the expression of EMP1, EMP2, and EMP3 in invasive ductal carcinoma (IDC) of the breast, and investigate their clinical implications. Methods:In total, 418 IDC cases were collected, and specimens were used to construct a tissue microarray. Immunohistochemical staining of EMP1, EMP2, and EMP3 was performed and the results were analyzed in combination with the clinical data. Results:EMP1 was expressed in > 90% of all IDC subtypes. A decreased expression of EMP2 and EMP3 was observed in triple-negative breast cancer. EMP3 expression was independently associated with human epidermal growth factor receptor 2 (HER2) positivity. HER2-negative cases exhibited a decreased EMP2 expression along with a higher histological grade and an increased proliferative index. No significant difference was found in the overall survival or disease-free survival based on the EMP expression. In HER2-negative breast cancer, EMP2 expression inversely correlated with the histological grade and proliferative index. Conclusion:EMP2 may be involved in the early stage of tumor development in hormone-positive breast cancer.

SUBMITTER: Cha YJ

PROVIDER: S-EPMC7462814 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Expression and Role of Epithelial Membrane Proteins in Tumorigenesis of Hormone Receptor-Positive Breast Cancer.

Cha Yoon Jin YJ Koo Ja Seung JS

Journal of breast cancer 20200801 4

<h4>Purpose</h4>Studies on the expression of epithelial membrane proteins (EMPs) in breast cancer have been rare and limited. In the present study, we aimed to evaluate the expression of EMP1, EMP2, and EMP3 in invasive ductal carcinoma (IDC) of the breast, and investigate their clinical implications.<h4>Methods</h4>In total, 418 IDC cases were collected, and specimens were used to construct a tissue microarray. Immunohistochemical staining of EMP1, EMP2, and EMP3 was performed and the results w ...[more]

PMID: 32908789

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Project description:BackgroundAKT pathway activation is implicated in endocrine-therapy resistance. Data on the efficacy and safety of the AKT inhibitor capivasertib, as an addition to fulvestrant therapy, in patients with hormone receptor-positive advanced breast cancer are limited.MethodsIn a phase 3, randomized, double-blind trial, we enrolled eligible pre-, peri-, and postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer who had had a relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Patients were randomly assigned in a 1:1 ratio to receive capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors. Safety was assessed.ResultsOverall, 708 patients underwent randomization; 289 patients (40.8%) had AKT pathway alterations, and 489 (69.1%) had received a CDK4/6 inhibitor previously for advanced breast cancer. In the overall population, the median progression-free survival was 7.2 months in the capivasertib-fulvestrant group, as compared with 3.6 months in the placebo-fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P<0.001). In the AKT pathway-altered population, the median progression-free survival was 7.3 months in the capivasertib-fulvestrant group, as compared with 3.1 months in the placebo-fulvestrant group (hazard ratio, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The most frequent adverse events of grade 3 or higher in patients receiving capivasertib-fulvestrant were rash (in 12.1% of patients, vs. in 0.3% of those receiving placebo-fulvestrant) and diarrhea (in 9.3% vs. 0.3%). Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo.ConclusionsCapivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor. (Funded by AstraZeneca and the National Cancer Institute; CAPItello-291 ClinicalTrials.gov number, NCT04305496.).

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Dataset Information

Expression and Role of Epithelial Membrane Proteins in Tumorigenesis of Hormone Receptor-Positive Breast Cancer.

Publications

Expression and Role of Epithelial Membrane Proteins in Tumorigenesis of Hormone Receptor-Positive Breast Cancer.

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