340P - Microarray analysis of DNA copy number aberrations in breast tumor: correlation with the efficacy of neoadjuvant chemotherapy

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Locally Advanced
Translational Research
Presenter Nicolai Litviakov
Citation Annals of Oncology (2014) 25 (suppl_4): iv110-iv115. 10.1093/annonc/mdu328
Authors N.V. Litviakov1, N.V. Cherdyntseva1, M.M. Tsyganov1, P.V. Ivankovskaya2, E.M. Slonimskaya2
  • 1Laboratory Of Molecular Oncology And Immunology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, 634050 - Tomsk/RU
  • 2Department Of General Oncology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, 634050 - Tomsk/RU

Abstract

Aim

Neoadjuvant chemotherapy (NAC) is intensively used for the treatment of primary breast cancer to downstage tumors allowing breast-conserving surgery to be performed and hence to improve breast cancer (BC) survival. To find novel effective markers to predict NAC efficacy, we performed a combined analysis of copy number aberration (CNA) and deletion of multidrug resistance (MDR) gene loci in tumor DNA in relation to clinical response to NAC in BC patients.

Methods

CNA and deletions of MDR gene loci in biopsy specimens, collected before treatment were tested using high-density microarray platform CytoScanTM HD Array (Affymetrix, USA). 68 BC patients were treated with 4 courses of anthracycline-based neoadjuvant chemotherapy. The immediate tumor response to NAC was measured in accordance with WHO recommendations.

Results

In breast tumors, structural CNA in 1q, 8p, 8q, 11q, 16q, 17p chromosomal regions were observed most frequently. 1q43 amplification correlated with good response to NAC. Partial tumor regression was observed in 83% (33/39) of patients with 1q43 amplification, whereas no response to NAC was found in 78% (18/23) of patients with normal 1q43 region (р = 1.18x10−6, Fisher's test,). Amplification in 1q43 along with deletion in 18р11.21 loci resulted in partial tumor regression in 92% (35/38) of patients. In the case of the normal status of these loci, 81% (21/26) of patients had no response to NAC (р = 2.26x10−9). All patients with deletions of АВСВ1, АВСВ3, ABCC5 gene loci –7q21.1, 6p21.32, 3q27 correspondingly, and most patients having deletions in АВСС1 (16p13.1), АВСС2 (10q24), ABCG1 (21q22.3), ABCG2 (4q22.1), responded favorably to NAC.

Conclusions

The presence of unbalanced chromosome abnormalities in 1q, 18p loci and the loss of chromosomal loci containing the MDR gene within breast tumors correlates with good response to NAC and can be considered as a promising marker for predicting response to neoadjuvant chemotherapy with high confidence value. Acknowledgments: RFBR project 13-04-98111 р_sibir_а.

Disclosure

All authors have declared no conflicts of interest.