Breast Cancer Research and Treatment

, Volume 134, Issue 1, pp 229–236

14-3-3σ expression is associated with poor pathological complete response to neoadjuvant chemotherapy in human breast cancers

  • Yukiko Nakamura
  • Kazuteru Oshima
  • Yasuto Naoi
  • Takahiro Nakayama
  • Seung Jin Kim
  • Kenzo Shimazu
  • Atsushi Shimomura
  • Naomi Maruyama
  • Yasuhiro Tamaki
  • Shinzaburo Noguchi
Preclinical Study

DOI: 10.1007/s10549-012-1976-x

Cite this article as:
Nakamura, Y., Oshima, K., Naoi, Y. et al. Breast Cancer Res Treat (2012) 134: 229. doi:10.1007/s10549-012-1976-x

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.

Keywords

14-3-3σTP53ChemotherapyBreast cancer

Supplementary material

10549_2012_1976_MOESM1_ESM.doc (62 kb)
Supplementary Table 1 (DOC 62 kb)
10549_2012_1976_MOESM2_ESM.jpg (146 kb)
Supplementary Fig. 1.14-3- promoter hypermethylation and 14-3-3σ protein expression. Immunohistochemical staining results for six tumors with 14-3- promoter hypermethylation. M, amplification with methylated primers; U, amplification with unmethylated primers. Scale bars: 200 μm. Marker: 200 bp DNA ladder marker. (JPG 147 kb)

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Yukiko Nakamura
    • 1
  • Kazuteru Oshima
    • 1
  • Yasuto Naoi
    • 1
  • Takahiro Nakayama
    • 1
  • Seung Jin Kim
    • 1
  • Kenzo Shimazu
    • 1
  • Atsushi Shimomura
    • 1
  • Naomi Maruyama
    • 1
  • Yasuhiro Tamaki
    • 1
  • Shinzaburo Noguchi
    • 1
  1. 1.Department of Breast and Endocrine SurgeryOsaka University Graduate School of MedicineOsakaJapan