Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 134, Issue 1, Pages 229-236Publisher
SPRINGER
DOI: 10.1007/s10549-012-1976-x
Keywords
14-3-3 sigma; TP53; Chemotherapy; Breast cancer
Categories
Funding
- Ministry of Health, Labour and Welfare, Japan
- Pfizer
- Bristol-Myers Squibb.
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14-3-3 sigma 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 14-3-3 sigma 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 14-3-3 sigma 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 14-3-3 sigma. There was no significant association between 14-3-3 sigma expression and TP53 mutation or p53 expression. However, 14-3-3 sigma expression showed a significantly (P = 0.009) negative association with pathological complete response (pCR) to P-FEC, and multivariate analysis demonstrated that only 14-3-3 sigma (P = 0.015) and estrogen receptor (P = 0.021) were significantly and independently associated with pCR. The combination of 14-3-3 sigma expression and TP53 mutation status had an additive negative effect on pCR, i.e., pCR rates were 45.5% for 14-3-3 sigma negative/TP53 mutant tumors, 24.6% for 14-3-3 sigma negative/TP53 wild tumors, 23.1% for 14-3-3 sigma positive/TP53 mutant tumors, and 0% for 14-3-3 sigma positive/TP53 wild tumors. These results demonstrate that 14-3-3 sigma expression is significantly associated with resistance to P-FEC and this association is independent of other biological markers. The combination of 14-3-3 sigma expression and TP53 mutation status has an additively negative effect on the response to P-FEC.
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