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Updated: May 25, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
14-3-3σ expression is associated with poor pathological complete response to neoadjuvant chemotherapy in human breast
Yukiko Nakamura1, Kazuteru Oshima, Yasuto Naoi
1Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Abstract:
14-3-3σ is a tumor suppressor gene induced by p53 in response to DNA damage and reportedly associated with resistance to chemotherapy. The aim of this study was to investigate whether 14-3-3σ expression is also associated with resistance to neoadjuvant chemotherapy consisting of paclitaxel followed by 5-FU/epirubicin/cyclophosphamide (P-FEC) in human breast cancer patients. A total of 123 primary breast cancer patients treated with neoadjuvant chemotherapy (P-FEC) were included in this study. Immunohistochemistry of 14-3-3σ and p53 as well as direct sequencing of TP53 were performed using the tumor biopsy samples obtained prior to neoadjuvant chemotherapy. Thirty-eight of the tumors (31%) were positive for 14-3-3σ. There was no significant association between 14-3-3σ expression and TP53 mutation or p53 expression. However, 14-3-3σ expression showed a significantly (P=0.009) negative association with pathological complete response (pCR) to P-FEC, and multivariate analysis demonstrated that only 14-3-3σ (P=0.015) and estrogen receptor (P=0.021) were significantly and independently associated with pCR. The combination of 14-3-3σ expression and TP53 mutation status had an additive negative effect on pCR, i.e., pCR rates were 45.5% for 14-3-3σ negative/TP53 mutant tumors, 24.6% for 14-3-3σ negative/TP53 wild tumors, 23.1% for 14-3-3σ positive/TP53 mutant tumors, and 0% for 14-3-3σ positive/TP53 wild tumors. These results demonstrate that 14-3-3σ expression is significantly associated with resistance to P-FEC and this association is independent of other biological markers. The combination of 14-3-3σ expression and TP53 mutation status has an additively negative effect on the response to P-FEC.
Insights
High 14-3-3σ expression in breast cancer predicts resistance to neoadjuvant chemotherapy (P-FEC). This association is independent of TP53 mutations, suggesting 14-3-3σ as a resistance biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- 14-3-3σ is a tumor suppressor gene linked to chemotherapy resistance.
- Its role in response to neoadjuvant chemotherapy in breast cancer requires further investigation.
Purpose of the Study:
- To investigate the association between 14-3-3σ expression and treatment response in breast cancer patients receiving neoadjuvant P-FEC chemotherapy.
- To determine if 14-3-3σ expression is an independent predictor of pathological complete response (pCR).
Main Methods:
- Immunohistochemistry and direct sequencing of TP53 were performed on tumor samples from 123 breast cancer patients.
- Patients received neoadjuvant paclitaxel followed by 5-FU/epirubicin/cyclophosphamide (P-FEC).
- Association between 14-3-3σ expression, TP53 mutation status, and pCR was analyzed.
Main Results:
- 31% of tumors showed positive 14-3-3σ expression.
- 14-3-3σ expression was significantly associated with a lower pathological complete response (pCR) rate (P=0.009).
- Multivariate analysis confirmed 14-3-3σ and estrogen receptor status as independent predictors of pCR.
Conclusions:
- 14-3-3σ expression is significantly associated with resistance to neoadjuvant P-FEC chemotherapy in breast cancer.
- The combination of 14-3-3σ expression and TP53 mutation status additively reduces pCR rates.
- 14-3-3σ is a potential biomarker for predicting response to P-FEC chemotherapy, independent of other markers.