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FOXC1 overexpression is a marker of poor response to anthracycline-based adjuvant chemotherapy in sporadic triple-negative breast cancer.

ABSTRACT: Because of its aggressive characteristics and poor prognosis, triple-negative breast cancer (TNBC) has become a hot topic in cancer research. Chemotherapy is currently the only treatment for patients with TNBC. The transcription factor FOXC1 has been associated with TNBC prognosis, but little is known about its effect on chemosensitivity. The aim of this study was to investigate the effects of FOXC1 on chemosensitivity.A case-control study was performed on 25 TNBC patients who experienced relapse and/or metastasis. Another 25 patients without relapse or metastasis were randomly selected as controls. Medical records were reviewed for relevant information, and immunohistochemistry was performed to measure FOXC1 levels. The Kaplan-Meier method and Cox analysis were used to analyze differences in disease-free survival (DFS) and overall survival (OS). The correlation of FOXC1 expression with chemosensitivity was analyzed. Data were analyzed using SPSS 21.0 software, and a P value <0.05 was considered to be statistically significant.In 15 of 22 case patients, FOXC1 was overexpressed, whereas only 8 control patients exhibited FOXC1 overexpression (P < 0.05). FOXC1 expression had no correlation with pathological indicators. An anthracycline-based regimen was administered to 21 study patients and 23 control patients. FOXC1 expression was significantly associated with a worse DFS (HR 2.62, 95% CI 1.05-6.50, P = 0.038) but presented no correlation with OS (HR 2.53, 95% CI 0.76-8.40, P = 0.131) among these 44 patients.This study shows that FOXC1 is correlated with chemosensitivity to anthracycline and could be used as an indicator of chemosensitivity in sporadic TNBC.

SUBMITTER: Xu YL

PROVIDER: S-EPMC5438824 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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FOXC1 overexpression is a marker of poor response to anthracycline-based adjuvant chemotherapy in sporadic triple-negative breast cancer.

Xu Y L YL Yao R R Li J J Zhou Y D YD Mao F F Pan B B Sun Q Q

Cancer chemotherapy and pharmacology 20170510 6

<h4>Purpose</h4>Because of its aggressive characteristics and poor prognosis, triple-negative breast cancer (TNBC) has become a hot topic in cancer research. Chemotherapy is currently the only treatment for patients with TNBC. The transcription factor FOXC1 has been associated with TNBC prognosis, but little is known about its effect on chemosensitivity. The aim of this study was to investigate the effects of FOXC1 on chemosensitivity.<h4>Methods</h4>A case-control study was performed on 25 TNBC ...[more]

PMID: 28493031

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Project description:Triple-negative breast cancer (TNBC) constitutes a heterogeneous breast cancer subgroup with poor prognosis; survival rates are likely to be lower with TNBC compared to other breast cancer subgroups. For this disease, systemic adjuvant chemotherapy regimens often yield suboptimal clinical results. To improve treatment regimens in TNBC, identification of molecular biomarkers may help to select patients for individualized adjuvant therapy. Evidence has accumulated that determination of the methylation status of the PITX2 gene provides a predictive value in various breast cancer subgroups, either treated with endocrine-based therapy or anthracycline-containing chemotherapy. To further explore the validity of this novel predictive candidate biomarker, in the present exploratory retrospective study, determination of the PITX2 DNA-methylation status was assessed for non-metastatic TNBC patients treated with adjuvant anthracycline-based chemotherapy by molecular analysis of breast cancer tissues. The PITX2 DNA-methylation status was determined in fresh-frozen tumor tissue specimens (n=56) by methylation-specific qRT-PCR (qMSP) and the data related to disease-free and overall survival, applying an optimized DNA-methylation score of 6.35%. For non-metastatic TNBC patients treated with adjuvant systemic anthracycline-based chemotherapy, a low PITX2 DNA-methylation status (<6.35) defines TNBC patients with poor disease-free and overall survival. Univariate and multivariate analyses demonstrate the statistically independent predictive value of PITX2 DNA-methylation. For non-metastatic TNBC patients, selective determination of the PITX2 DNA-methylation status may serve as a cancer biomarker for predicting response to anthracycline-based adjuvant chemotherapy. The assay based on methylation of the PIXT2 gene can be applied to frozen and routinely available formalin-fixed, paraffin-embedded (FFPE) breast cancer tumor tissues that will not only define those TNBC patients who may benefit from anthracycline-based chemotherapy but also those who should be spared the necessity of such potentially toxic treatment. Such patients should be allocated to alternative treatment options.

Dataset Information

FOXC1 overexpression is a marker of poor response to anthracycline-based adjuvant chemotherapy in sporadic triple-negative breast cancer.

Publications

FOXC1 overexpression is a marker of poor response to anthracycline-based adjuvant chemotherapy in sporadic triple-negative breast cancer.

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