Promoter methylation of BRCA1 in triple-negative breast cancer predicts sensitivity to adjuvant chemotherapy

Xu, Ye; Diao, Limei; Chen, Y.; Liu, Yiqiang; Wang, C.; Ouyang, Tao; Li, J.; Wang, T.; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Deng, Dajun; Narod, Steven A.; Xie, Yuxin

doi:10.1093/annonc/mdt011

Cited by 60 publications

(49 citation statements)

References 41 publications

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“…The overall progno- sis of TNBC in BRCA carriers and noncarriers is not significantly different within the first 5 years following an initial diagnosis [80]. In our study, we observed that TNBC patients with BRCA1 methylation had longer DFS compared with those without BRCA1 methylation, and OS outcome also showed similar correlation although, it is based on a single study [30]. Thus, based on our data BRCA1 methylation could be considered as a predictor for good prognosis in TNBC.…”

Section: Brca1/2supporting

confidence: 64%

A Meta-Analysis of Biomarkers for the Prognosis of Triple-Negative Breast Cancer Patients

Gui

Yang

et al. 2016

Biomark. Med.

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Section: Brca1/2supporting

confidence: 64%

A Meta-Analysis of Biomarkers for the Prognosis of Triple-Negative Breast Cancer Patients

Gui

Yang

et al. 2016

Biomark. Med.

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“…18,19 The BRCAness is identified in at least 25% of BRCA wild-type breast cancers and is more frequent in TNBC. 20,21 The BRCA1 promoter CpG island methylation is in approximately 30% of TNBC patients 22 and tumors with this methylation share the pattern of gene expression similar to inherited BRCA1-mutated breast cancers. 23 Pan-histone deacetylase inhibitor and many other strategies have been reported to induce BRCAness and then enable TNBC patients sensitive to platinum-based regimens.…”

Section: Molecular Mechanisms Of Platinum and Homologous Recombinatiomentioning

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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“…BRCA1germline mutations carriers often present tumors with basal-like morphology and their genomic alterations, as examined by microarray-based comparative genomic hybridization (array CGH), are similar to those in TNBC patients [10] . Finally, BRCA1 promoter methylation is a frequent event in TNBC patients and it predicts sensitivity to adjuvant chemotherapy [38] . In cancer cell lines and xenografted tumors, BRCA1CpG island promoter hypermethylation-associated silencing predicts enhanced sensitivity to platinum-derived drugs to the same extent as BRCA1 mutations.…”

Section: Neoadjuvant Chemotherapy In Tnbcmentioning

confidence: 99%

The recent progress of neoadjuvant chemotherapy in triple negative breast cancer: A short review

Liontos

Karageorgopoulou²,

Michalaki³

et al. 2015

JST

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Triple negative breast cancer (TNBC) encompasses tumors that do not express either the estrogen receptor (ER) or the progesterone receptor (PR) and also do not overexpress the Human Epidermal growth factor Receptor 2 (HER2). This is a heterogenous group of tumors that significantly overlaps with both basal-like tumors and BRCA1/BRCA2 mutationassociated tumors. TNBC is highly aggressive in nature and exhibits worse prognosis than the other subtypes of breast cancer, despite its increased chemosensitivity. Neoadjuvant chemotherapy (NACT) is a treatment option regularly incorporated in clinical practice to improve subsequent surgical management. In parallel, allows rating of the pathological compete response (pCR) which is associated with the prognosis of these patients and evaluates the efficacy of the applied treatment as well. Platinum-based regimens and novel targeted therapies have shown some benefit in TNBC, though an unmet need for improved therapeutic strategies in this patient population still remains. In this review, the latest progresses in NACT in TNBC are discussed, along with the improved understanding of molecular targets and useful biomarkers in this group of patients.

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Promoter methylation of BRCA1 in triple-negative breast cancer predicts sensitivity to adjuvant chemotherapy

Cited by 60 publications

References 41 publications

A Meta-Analysis of Biomarkers for the Prognosis of Triple-Negative Breast Cancer Patients

A Meta-Analysis of Biomarkers for the Prognosis of Triple-Negative Breast Cancer Patients

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

The recent progress of neoadjuvant chemotherapy in triple negative breast cancer: A short review

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