14-3-3σ expression is associated with poor pathological complete response to neoadjuvant chemotherapy in human breast cancers.
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.
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Yukiko
Y
Nakamura
Kazuteru
K
Oshima
Yasuto
Y
Naoi
Takahiro
T
Nakayama
Seung Jin
SJ
Kim
Kenzo
K
Shimazu
Atsushi
A
Shimomura
Naomi
N
Maruyama
Yasuhiro
Y
Tamaki
Shinzaburo
S
Noguchi
D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000008:administration & dosage; D005092:Exonucleases / Q000235:genetics / Q000378:metabolism*; D005095:Exoribonucleases; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D015251:Epirubicin; D003520:Cyclophosphamide; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D017239:Paclitaxel; D005472:Fluorouracil