Abstract P2-09-17: Limited Gene Expression Profiling as Predictor of Response to Neoadjuvant Chemotherapy (NCT) with Docetaxel, Doxorubicin, Cyclophosphamide (TAC), or AC and Nab-Paclitaxel and Carboplatin +/− Trastuzumab in Patients (pts) with Locally Advanced (LABC) Stage II-III and Inflammatory Breast Cancer (IBC)
Authors: Somlo G , Frankel P , Cooc J , Lau S , Danenberg K , Yim J , Danenberg P. 
Published: April 2011

Abstract
Background: Pathologic complete response (pCR) following neoadjuvant therapy (NCT) may predict for improved survival. Hence, more effective and individualized/targeted NCT regimens in conjunction with molecular markers that predict for both response and/or resistance are needed. Materials and Methods: 119 evaluable pts (121 enrolled) with stages II/III LABC/IBC were prospectively randomized to receive 6 cycles of docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 with filgrastim support (TAC, arm A) versus a novel regimen of A 60 mg/m2 and C 600 mg/m2 given every 2 weeks x 4, followed by 3 weekly doses of carboplatin (AUC 2) and nab-paclitaxel 100 mg/m2 repeated as 28 day cycles x 3 (arm B). Pts with HER2 overexpressing (HER2+) BC received NCT similar to arm B, but with the addition of 12 weekly doses of trastuzumab given together with carboplatin and nab-paclitaxel (arm C). Core biopsies were performed prior to NCT and samples from 10 micron thick slides of formalin-fixed and paraffin-embedded (FFPE) breast cancer tissue were microdissected, and RNA was extracted for assessment of gene expression by RT-PCR for a panel of genes involved in cell proliferation, tumor suppression, DNA repair, and apoptosis. The following genes were evaluated: HER2/neu, IGF-1R, JAK2, STAT3, EGFR, BRCA1 and 2, PARP1, ERCC1, Topoisomerase 2-alpha, BBC3 (PUMA), p21, p27, IRF1, Beta-catenin, and SPARC, with actin as control. Responses were separated as complete or other response, and the Wilcoxon test was applied. Results: Neoadjuvant response assessment and sufficient amount of RNA following microdissection of primary tumor slides were available in 66/121 pts (55%). These 66 pts had similar characteristics to the entire cohort of enrolled pts. The median age was 51 yrs (range 30-69), and pts were treated for stage II/III BC (N=32, N=34, respectively, with 10 IBC cases). 37 pts were treated on Arms A and B (HER2- cohorts), and 29 on arm C (HER2+ cohort). pCR rates were 5/37 (14%) in groups A and B (of this set) combined, and 14/29 (48%) in group C (HER2+). For all arms/pts combined, overexpression of HER2, EGFR, and BRCA2, and low expression of p27, and IGFR1 were observed in pts with pCR, in comparison to pts not achieving pCR (P&lt;0.05). When the analysis was restricted to HER2 negative cases (Arms A and B), BRCA2, JAK2 overexpression, and low expression of IGF1R were associated with pCR (P&lt;0.05). Conclusion: Limited gene array analysis from microdissected FFPE specimens procured prior to NCT is feasible, and there is sufficient evidence in this limited data set to suggest that the specifc gene expression levels tested may play an important role in determining response to NCT both in HER2+ and HER2-, locally advanced, and inflammatory breast cancer.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-17.