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Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy
Juan Jin1, Wenwen Zhang1, Wenfei Ji2
1a Department of Medical Oncology , Jinling Hospital, Medical School of Nanjing University , Nanjing , China.
Abstract:
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.
Insights
Platinum chemotherapy is vital for triple-negative breast cancer (TNBC), but resistance is common. Homologous recombination deficiency (HRD), indicated by BRCA mutations or high HRD scores, predicts response to platinum agents in TNBC.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) presents significant treatment challenges.
- Platinum-based chemotherapy is a cornerstone for TNBC, yet response rates vary due to resistance.
- Understanding platinum resistance mechanisms is crucial for improving patient outcomes.
Purpose of the Study:
- To review preclinical and clinical studies on platinum efficacy in TNBC.
- To summarize mechanisms underlying platinum response and resistance.
- To identify potential predictive biomarkers for platinum sensitivity in TNBC.
Main Methods:
- Literature review of preclinical and clinical investigations.
- Analysis of studies focusing on homologous recombination deficiency (HRD) and BRCA function.
- Evaluation of biomarkers such as BRCA mutations, methylation, BRCA-like classifier, and HRD scores.
Main Results:
- Homologous recombination deficiency (HRD), often due to BRCA dysfunction, is a key predictor of platinum efficacy.
- BRCA mutations, methylation, BRCA-like classifier, and HRD scores show promise as predictive biomarkers.
- p53 family members, TNBC molecular subtypes, tumor-infiltrating lymphocytes, and thrombocytopenia are emerging predictive factors.
Conclusions:
- An HR deficiency profile, including BRCA mutations and high HRD scores, can predict response to platinum and other DNA-damaging agents in TNBC.
- Identifying these biomarkers can guide personalized treatment strategies for TNBC patients.
- Further research into alternative biomarkers may enhance treatment selection and efficacy.
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