Gene signature‐based prediction of triple‐negative breast cancer patient response to Neoadjuvant chemotherapy

Abstract

Neoadjuvant chemotherapy is the current standard of care for large, advanced, and/or inoperable tumors, including triple‐negative breast cancer. Although the clinical benefits of neoadjuvant chemotherapy have been illustrated through numerous clinical trials, more than half of the patients do not experience therapeutic benefit and needlessly suffer from side effects. Currently, no clinically applicable biomarkers are available for predicting neoadjuvant chemotherapy response in triple‐negative breast cancer; the discovery of such a predictive biomarker or marker profile is an unmet need. In this study, we introduce a generic computational framework to calculate a response‐probability score (RPS), based on patient transcriptomic profiles, to predict their response to neoadjuvant chemotherapy. We first validated this framework in ER‐positive breast cancer patients and showed that it predicted neoadjuvant chemotherapy response with equal performance to several clinically used gene signatures, including Oncotype DX and MammaPrint. Then, we applied this framework to triple‐negative breast cancer data and, for each patient, we calculated a response probability score (TNBC‐RPS). Our results indicate that the TNBC‐RPS achieved the highest accuracy for predicting neoadjuvant chemotherapy response compared to previously proposed 143 gene signatures. When combined with additional clinical factors, the TNBC‐RPS achieved a high prediction accuracy for triple‐negative breast cancer patients, which was comparable to the prediction accuracy of Oncotype DX and MammaPrint in ER‐positive patients. In conclusion, the TNBC‐RPS accurately predicts neoadjuvant chemotherapy response in triple‐negative breast cancer patients and has the potential to be clinically used to aid physicians in stratifying patients for more effective neoadjuvant chemotherapy.

Derived Neutrophil-to-Lymphocyte Ratio Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer

“…This finding suggests that administration of chemotherapy may affect the immune system within the tumor, inducing inflammation that somehow could limit the efficacy of the chemotherapy (29). Alternatively, it is known that chemotherapy can stimulate an immunologic cell death, which depends on the tumor type and the specific genomic and stromal microenvironment and could favor the efficacy of chemotherapy (30). Assessment of dNLR in TNBC using the optimal cutoff showed a negative association with pCR in the Cox regression model at baseline and at the EOT dNLR.…”

New Advances in the Research of Resistance to Neoadjuvant Chemotherapy in Breast Cancer

“…5 Trastuzumab can induce nuclear HER4 up-regulation and nuclear HER2 translocation. 6 Over-expression of NF-κB, Bcl-2 and c-Flip can inhibit cell apoptosis. 7 Endoplasmic reticulum stress or DNA damage can induce autophagy.…”

“…Although the efficacy of neoadjuvant chemotherapy has been confirmed, clinical trial data show that the effects of neoadjuvant chemotherapy for different breast cancer patients are very different, and it is easy to develop drug resistance, which is not conducive to subsequent treatment [6]. Drug resistance to neoadjuvant chemotherapy is one of the main reasons for its treatment failure, and it is one of the most challenging problems in the treatment of breast cancer today.…”

“…Drugs that directly or indirectly damage DNA can induce breast cancer cells to produce DDR 5. Trastuzumab can induce nuclear HER4 up-regulation and nuclear HER2 translocation 6. Over-expression of NF-κB, Bcl-2 and c-Flip can inhibit cell apoptosis 7.…”

Using Breast Cancer Gene Expression Signatures in Clinical Practice: Unsolved Issues, Ongoing Trials and Future Perspectives

“…Many processes are involved in chemosensitivity and chemoresistance, and they differentially account in each tumor subtype [ 83 ]. Zhao et al developed a response probability score (RPS), which differentially involved markers of tumor cell proliferation rate, immune cell infiltration and stromal cell abundance in all-coming and triple-negative tumors [ 99 ].…”