Identification and use of biomarkers in treatment strategies for triple‐negative breast cancer subtypes

Lehmann, Brian D.; Pietenpol, Jennifer A.

doi:10.1002/path.4280

Cited by 377 publications

(412 citation statements)

References 67 publications

(106 reference statements)

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“…The LAR subtype is associated with high androgen receptor (AR) expression levels. 94,95 The miRNA expression profiles of these molecular subtypes of TNBC might differ.…”

Section: Mirna In Triple-negative Breast Cancermentioning

confidence: 99%

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

et al. 2016

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MicroRNAs (miRNAs) are short non-coding RNAs that regulate the function of target genes at the post-transcriptional phase. miRNAs are considered to have roles in the development, progression and metastasis of cancer. Recent studies have indicated that particular miRNA signatures are correlated with tumor aggressiveness, response to drug therapy and patient outcome in breast cancer. On the other hand, in routine clinical practice, the treatment regimens for breast cancer are determined based on the intrinsic subtype of the primary tumor. Previous studies have shown that miRNA expression profiles of each intrinsic subtypes of breast cancer differ. In hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, miRNA expressions are found to be correlated with endocrine therapy resistance, progesterone receptor expression and heat shock protein activity. Some miRNAs are associated with resistance to HER2-targeted therapy and HER3 expression in HER2-positive breast cancer. In triple-negative breast cancer, miRNA expressions are found to be associated with BRCA mutations, immune system, epithelial-mesenchymal transition, cancer stem cell properties and androgen receptor expression. As it has been clarified that the expression levels and functions of miRNA differ among the various subtypes of breast cancer, and it is necessary to take account of the characteristics of each breast cancer subtype during research into the roles of miRNA in breast cancer. In addition, the discovery of the roles played by miRNAs in breast cancer might provide new opportunities for the development of novel strategies for diagnosing and treating breast cancer.

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“…The LAR subtype is associated with high androgen receptor (AR) expression levels. 94,95 The miRNA expression profiles of these molecular subtypes of TNBC might differ.…”

Section: Mirna In Triple-negative Breast Cancermentioning

confidence: 99%

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

et al. 2016

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“…28 Xenograft tumors derived from BRCA1-deficient TNBC cell lines also show cisplatin sensitivity. 29 In a group of BRCA1-mutated breast cancers after neoadjuvant chemotherapy, pathologic complete response (pCR) was observed in 10 (83%) of 12 breast cancer patients treated with cisplatin. 30 Many prospective studies of early-stage and metastatic TNBC have confirmed that BRCA-mutation status is a potential predictive biomarker.…”

Section: Brca Expressionmentioning

confidence: 99%

“…53 Retrospective trials have found that molecular profiles of TNBC have clinical utility in predicting chemotherapy response. 29,54 In a clinical research of 1055 patients with TNBC, BLBC or both, only when TNBC can be stratified into BLBC subtype could patients be identified with notably better response after chemotherapy. 55 Previous studies show that BLBC harbors the hallmarks of BRCAness.…”

Section: Molecular Subtype Associated Biomarkersmentioning

confidence: 99%

Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy

Jin

Zhang

et al. 2017

Cancer Biology & Therapy

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Treatment of triple negative breast cancer (TNBC) has been a big challenge since it is defined. To date, platinum-based chemotherapy has played a significant role in the treatment of TNBC patients. However, some patients do not respond to platinum salts or gradually develop chemoresistance, resulting in little effect, or even some adverse effects. Here, we review numerous preclinical and clinical investigations to summarize possible mechanisms and potential predictive biomarkers of platinum in TNBC. The homologous recombination deficiency (HRD) resulting from the loss of BRCA function is the main rationale of platinum efficacy in TNBC. BRCA mutation and methylation have been demonstrated to be important potential biomarkers. Based on genome-wide effects, BRCA-like classifier can identify the functional loss of BRCA and work as the predictor. HRD score that is able to identify the "BRCAness" and predict the sensitivity of platinum is increasingly considered. Taken together, all findings suggest that HR deficiency profile encompassed by BRCA mutation and high HRD score could predict response to platinum, even to other DNA-damage inducing agents. p53 family members and molecular subtypes of TNBC are also important alternative considerations for predicting platinum response based on the preclinical trials. Currently, tumor infiltrating lymphocyte level and thrombocytopenia are emerging as predictive biomarkers.

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“…The reason may be that the normal-like subtype, classified according to the gene expression profile, included 60% of ERpositive tumors and thus did not match the non-basal-like phenotype based on IHC. Moreover, Lehmann and colleagues reported a 7-subtype molecular classification of TNBC, in which they distinguished between 2 basal-like subtypes: BL1 and BL2 (30). Masuda and colleagues recently demonstrated that among the 7 TNBC subtypes, the BL1 subtype had the highest chemosensitivity (pCR rate ¼ 52%) whereas the BL2 subtype had the lowest one (pCR rate ¼ 0%; ref.…”

Section: Biologic Biomarkers Of Tumor Responsementioning

confidence: 99%

Identification of Biomarkers Including 18FDG-PET/CT for Early Prediction of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

Humbert

Riedinger

Charon-Barra

et al. 2015

Clinical Cancer Research

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Purpose: To investigate the value of the metabolic tumor response assessed with 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiologic markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in women with triple-negative breast cancer (TNBC).Experimental Design: Fifty consecutive women with TNBC and an indication for NAC were prospectively included. Different pretreatment clinical, biologic, and pathologic biomarkers, including SBR grade, the Ki-67 proliferation index, androgen receptor expression, EGF receptor (EGFR), and cytokeratin 5/6 staining, were assessed. Tumor glucose metabolism at baseline and its change after the first cycle of NAC (DSUV max ) were assessed using FDG-PET.Results: The pCR rate was 42%. High Ki-67 proliferation index (P ¼ 0.016), negative EGFR status (P ¼ 0.042), and high DSUV max (P ¼ 0.002) were significantly associated with pCR. In multivariate logistic regression, both negative EGFR status (OR, 6.4; P ¼ 0.043) and high DSUV max (OR, 7.1; P ¼ 0.014) were independent predictors of pCR. Using a threshold at À50%, tumor DSUV max predicted pCR with a negative, a positive predictive value, and an accuracy of 79%, 70%, and 75%, respectively. Combining a low DSUV max and positive EGFR status could predict non-pCR with an accuracy of 92%.Conclusions: It is important to define the chemosensitivity of TNBC to NAC early. Combining EGFR status and the metabolic response assessed with FDG-PET can help the physician to early predict the probability of achieving pCR or not. Given these results, the interest of response-guided tailoring of the chemotherapy might be tested in multicenter trials.

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Identification and use of biomarkers in treatment strategies for triple‐negative breast cancer subtypes

Cited by 377 publications

References 67 publications

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy

Identification of Biomarkers Including 18FDG-PET/CT for Early Prediction of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

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