204P - DJ-1 protein expression in intrinsic subtype as a predictor of pathological complete remission after neoadjuvant chemotherapy in breast cancer pati...

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer
Translational Research
Presenter Hiroshi Kaise
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors H. Kaise1, T. Kawate1, K. Iwaya2, K. Yamada1, T. Ishikawa1, N. Kohno3
  • 1Breast Oncology, Tokyo Medical University Hospital, 160-0023 - Tokyo/JP
  • 2Basic Pathology, National Defence Medical College, 359-8513 - Saitama/JP
  • 3Breast Oncology, Kobe Kaisei Hospital, 657-0068 - Kobe/JP

Abstract

Aim

The DJ-1 gene was originally identified as an oncogene that, in conjunction with activated ras, and Parkinson's disease is associated with DJ-1/Parkinson protein 7 dysfunction. Neoplastic transformation is associated with the hyperactivity of DJ-1 . DJ-1 overexpression increases the resistance of neoplastic cells to apoptosis by inhibiting the phosphatase and tensin homolog(PTEN)-mediated protein kinase B/Akt pathway and/or other apoptotic pathways,including death-associated protein 6 and homeodomain-interacting protein kinase1. Recent genetic studies showed that, in addition to apoptosis pathways, DJ-1 is also involved in cellular defense against reactive oxygen species. The activity of apoptotic and cellular defense pathways is key in determining drug sensitivity. DJ-1 overexpression is associated with various cancers. We reported that low DJ-1 protein expression is a significant predictor of pCR after chemotherapy in reast cancer patients.(Kawate, BCRT2013) In this time, we will report that we classified Luminal-A subtype to new Lum-A and Lum-B subtype by ki67 and reanalyzed results.

Methods

Expression of DJ-1 in pre-therapeutic needle biopsies and surgical specimens obtained from 198 breast cancer cases that received neoadjuvant chemotherapy was determined using immunohistochemistry and in situ hybridization.Chemotherapy comprised epirubicin / cyclophosphamide taxane-based regimens with or without trastuzumab. Univariate and multivariate analyses were used to evaluate the predictive value of DJ-1 on pCR.

Results

Low DJ-1 protein expression was detected in 46.0 % (91/198) of all breast cancer cases and in 80.4 % (37/46) of pCR cases. In multivariate analysis, DJ-1 expression(χ2 = 16.05, p < 0.0001)and HER2 status (χ2 = 6.51, p = 0.01), in contrast to hormone receptors status, Ki-67 labeling index, were significant predictors of pCR. In Intrinsic Sub type, the pCR rates and p-value(univariate analysis) is 33.3% and p = 0.0177 (in luminal A), is 26.1% and p = 0.0134(in lum-B), is 44% and p = 0.0097 (lum-HER2), is 60% and p = 0.46 (HER2 type) and is 42.1% and p = 0.0159 (Triple negative) by the Low DJ-1 expression.

Conclusions

Low DJ-1 protein expression is a significant predictor of pCR after neoadjuvant chemotherapy at any Sub Type in breast cancer patients.

Disclosure

All authors have declared no conflicts of interest.