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 Anticancer Agents
Breast Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Therapy
Biological Therapy
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.