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Androgen receptor expression predicts different clinical outcomes for breast cancer patients stratified by hormone receptor status.

ABSTRACT: In this study we sought to correlate androgen receptor (AR) expression with tumor progression and disease-free survival (DFS) in breast cancer patients. We investigated AR expression in 450 breast cancer patients. We found that breast cancers expressing the estrogen receptor (ER) are more likely to co-express AR compared to ER-negative cancers (56.0% versus 28.1%, P < 0.001). In addition, we found that AR expression is correlated with increased DFS in patients with luminal breast cancer (P < 0.001), and decreased DFS in TNBC (triple negative breast cancer, P = 0.014). In addition, patients with HR+ tumors (Hormone receptor positive tumors) expressing low levels of AR have the lowest DFS among all receptor combinations. We also propose a novel prognostic model using AR receptor status, BRCA1, and present data showing that our model is more predictive of disease free survival compared to the traditional TMN staging system.

SUBMITTER: Jiang HS

PROVIDER: S-EPMC5173059 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Androgen receptor expression predicts different clinical outcomes for breast cancer patients stratified by hormone receptor status.

Jiang He-Sheng HS Kuang Xia-Ying XY Sun Wei-Li WL Xu Yan Y Zheng Yi-Zi YZ Liu Yi-Rong YR Lang Guan-Tian GT Qiao Feng F Hu Xin X Shao Zhi-Ming ZM

Oncotarget 20160701 27

In this study we sought to correlate androgen receptor (AR) expression with tumor progression and disease-free survival (DFS) in breast cancer patients. We investigated AR expression in 450 breast cancer patients. We found that breast cancers expressing the estrogen receptor (ER) are more likely to co-express AR compared to ER-negative cancers (56.0% versus 28.1%, P < 0.001). In addition, we found that AR expression is correlated with increased DFS in patients with luminal breast cancer (P < 0.0 ...[more]

PMID: 27285752

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Project description:Single estrogen receptor (ER)+ and progesterone receptor (PR)+ tumors account for about10% of all breast cancers. However, the prognosis of these single hormone receptor-positive (HR+) tumor remains unclear. We aimed to investigate the characteristics of single HR+ breast tumors according to HER2 status in order to improve the treatment of patients with single HR+. Patients from the SEER program (2010-2016) were divided into ER+PR-, ER-PR+, ER+PR+ and ER-PR- molecular subtypes stratified by HER2 status. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared by Kaplan-Meier curves after propensity score matching (PSM). A total of 203,406 patients were enrolled. Single ER+ and PR+ tumors account for 11.9% of the total population. For HER2- subtype, patients with ER+PR- (n = 16906 pairs) and ER-PR+ (n = 1395 pairs) had worse prognoses than those with ER+PR+ with hazard ratio (HR) and 95% confidence interval (CI) of 1.52 (1.41-1.64) and 2.25 (1.76-2.88) for OS; and 1.94 (1.76-2.14) and 2.57 (1.94-3.40) for BCSS, respectively; ER+PR- showed a better prognosis than ER-PR+ (n = 1394 pairs) and ER-PR- (n = 9626 pairs) with HR (95% CI) of 1.32 (1.06-1.65) and 1.44 (1.33-1.55) for OS, and 1.32 (1.03-1.69) and 1.46 (1.34-1.60) for BCSS, respectively; ER-PR+ had a similar prognosis relative to ER-PR- (n = 1395 pairs) after PSM. For HER2+ subtype, patients with ER-PR+, ER+PR-, and ER-PR- had similar OS and BCSS; ER+PR+ showed a similar prognosis compare with ER-PR+ (n = 535 pairs), but had better OS and BCSS than ER+PR- (n = 5376 pairs) and ER-PR- (n = 8143 pairs) after PSM. In addition, ER+PR+HER2+ showed similar OS and better BCSS compared with ER+PR+HER2- after PSM. In conclusion, single PR+ patients experienced poorer prognoses than single ER+ patients, and may be treated as ER-PR- patients in HER2- subtype. In HER2+ patients, both single ER+ and single PR+ cases showed similar prognoses compared with ER-PR- cases, and may be treated as ER-PR- patients.

Project description:We examined whether differences in tumor DNA methylation were associated with more aggressive hormone receptor-negative breast cancer in an ethnically diverse group of patients in the Breast Cancer Care in Chicago (BCCC) study and using data from The Cancer Genome Atlas (TCGA).DNA was extracted from formalin-fixed, paraffin-embedded samples on 75 patients (21 White, 31 African-American, and 23 Hispanic) (training dataset) enrolled in the BCCC. Hormone receptor status was defined as negative if tumors were negative for both estrogen and progesterone (ER/PR) receptors (N?=?22/75). DNA methylation was analyzed at 1505 CpG sites within 807 gene promoters using the Illumina GoldenGate assay. Differential DNA methylation as a predictor of hormone receptor status was tested while controlling for false discovery rate and assigned to the gene closest to the respective CpG site. Next, those genes that predicted ER/PR status were validated using TCGA data with respect to DNA methylation (validation dataset), and correlations between CpG methylation and gene expression were examined. In the training dataset, 5.7 % of promoter mean methylation values (46/807) were associated with receptor status at P?<?0.05; for 88 % of these (38/46), hypermethylation was associated with receptor-positive disease. Hypermethylation for FZD9, MME, BCAP31, HDAC9, PAX6, SCGB3A1, PDGFRA, IGFBP3, and PTGS2 genes most strongly predicted receptor-positive disease. Twenty-one of 24 predictor genes from the training dataset were confirmed in the validation dataset. The level of DNA methylation at 19 out 22 genes, for which gene expression data were available, was associated with gene activity.Higher levels of promoter methylation strongly correlate with hormone receptor positive status of breast tumors. For most of the genes identified in our training dataset as ER/PR receptor status predictors, DNA methylation correlated with stable gene expression level. The predictors performed well when evaluated on independent set of samples, with different racioethnic distribution, thus providing evidence that this set of DNA methylation biomarkers will likely generalize to prospective patient samples.

Project description:ObjectiveDifferent molecular subtypes of triple-negative breast cancer (TNBC) have previously been identified through analysis of gene expression profiles. The luminal androgen receptor (LAR) subtype has been shown to have a lower rate of pathologic complete response to neoadjuvant chemotherapy than other TNBC subtypes. The purpose of this study was to determine if the imaging features of TNBCs differ by AR (androgen receptor) status, which is a surrogate immunohistochemical (IHC) marker for the chemoresistant LAR subtype of TNBC.Materials and methodsThis sub-study was part of a clinical trial in patients with stage I-III TNBC who were prospectively monitored for response while receiving neoadjuvant systemic therapy (NAST) at a single comprehensive cancer center. This interim imaging analysis included 144 patients with known AR status measured by IHC. AR-positive (AR+) tumors were defined as those in which at least 10% of tumor cells had positive nuclear AR staining. Two experienced, fellowship-trained breast radiologists who were blinded to the IHC results retrospectively reviewed and reached consensus on all imaging studies for the index lesion (i.e., mammogram, ultrasound, and breast magnetic resonance imaging). The index lesion for each patient was reviewed and described according to the fifth edition of the Breast Imaging Reporting and Data System lexicon. Logistic regression modeling was used to identify imaging features predictive of AR status. p ≤ 0.05 was considered statistically significant.ResultsUnivariate logistic regression models for AR status showed that AR+ TNBC was significantly associated with heterogeneously dense breast composition on mammography (p = 0.02), mass with calcifications (p = 0.05), irregular mass shape on mammography (p = 0.03), and irregular mass shape on sonography (p = 0.003). Multivariate logistic regression models for AR status showed that AR+ TNBC was significantly associated with heterogeneously dense breast composition on mammography (p = 0.01), high mass density on mammography (p = 0.003), and irregular mass shape on sonography (p = 0.0004).ConclusionThe imaging features of TNBCs differ by AR status. Multimodality breast imaging may help identify the LAR subtype of TNBC, which has been shown to be a subtype that is relatively resistant to neoadjuvant chemotherapy.

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Androgen receptor expression predicts different clinical outcomes for breast cancer patients stratified by hormone receptor status.

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Androgen receptor expression predicts different clinical outcomes for breast cancer patients stratified by hormone receptor status.

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