Correlation of SPARC, ER, PR, and HER2 tumor with progression-free survival from a phase II neoadjuvant trial of gemcitabine, epirubicin, and nab-paclitaxel.

Abstract

618 Background: Neoadjuvant combinations of gemcitabine (G), anthracyclines and taxanes have demonstrated substantial activity with pCR rates of 20-25%. Secreted protein acidic rich in cysteine (SPARC) is an albumin binding protein that mediates intratumoral accumulation of nab-paclitaxel (nab-P) via a SPARC-albumin binding activity and is a poor prognostic factor for survival. This study was designed to evaluate the feasibility and safety of a biweekly schedule of neoadjuvant nab paclitaxel (nab-P) with G and epirubicin (E) with SPARC tumor assessments performed in consenting patients (pts). METHODS Eligibility: Clinical T1c-T4d and/or N0-3, M0 breast cancer (T1N0M0 excluded), normal LVEF. ER/PR/HER-2 obtained for all pts. TREATMENT neoadjuvant G 2,000 mg/m2, E 50 mg/m2, and nab-P 175 mg/m2 q14 days x 6 cycles followed by surgery. Post operative therapy: G 2,000 mg/m2 and nab-P 220 mg/m2 q14 days x 4 cycles. Myeloid growth factors were mandated with all cycles. Two different antibody reagents were used to probe for SPARC expression of tumoral SPARC and stromal SPARC; level 3 immunohistochemical (IHC) SPARC staining was considered positive. RESULTS 123 pts enrolled. Pathologic responses are available for 112 pts with 11 unevaluable. 82 pts consented to SPARC tumor testing. Median age 51 (29-72). Median tumor size 4.5 cm. 42% ER-/PR -. 55% clinical T3/T4 and 66% node positive. Pathologic complete responses (pCR) were noted in 22 pts (18%) with PRs in 84 pts (68%), and 6 SD (5%). SPARC IHC staining was available in 77 tumor samples; SPARC positivity was noted in 89% of evaluated tumors achieving pCR. Triple negative, ER negative or PR negative tumors were associated with worse PFS. SPARC + tumors showed a trend to improved PFS that was strongly associated with tumoral SPARC but not stromal SPARC. CONCLUSIONS Dose dense neoadjuvant G, E, and nab-P is active and well tolerated with a favorable pCR rate of 20%. ER neg, PR neg, and triple negative tumors were associated with worse PFS. Despite literature reports of SPARC positivity associated with poor prognosis, SPARC+ tumors in this study showed a high concordance with tumor response and a trend to improved PFS with tumoral SPARC. [Table: see text].

Cite this paper

@article{Inhorn2009CorrelationOS, title={Correlation of SPARC, ER, PR, and HER2 tumor with progression-free survival from a phase II neoadjuvant trial of gemcitabine, epirubicin, and nab-paclitaxel.}, author={Roger C. Inhorn and Brooke R. Daniel and Davey B Daniel and Yuval Naot and John D Zubkus and Chadrick Lane and Vuong Trieu and Dan Knauer and Nutan Desai and Denise A Yardley}, journal={Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, year={2009}, volume={27 15_suppl}, pages={618} }