Abstract P1-06-04: The predictive value of tumor-stroma ratio for radiological and pathological response to neoadjuvant chemotherapy in breast cancer (BC): A Dutch breast cancer trialists’ group (BOOG) side-study
Authors: Dekker TJA , Charehbili A , Smit VTHBM , Wasser MNJM , Heijns JB , van Warmerdam LJ , Kessels L , Dercksen W , Pepels M , Maartense E , van Laarhoven HWM , Vriens B , Meershoek-Klein Kranenbarg E , van de Velde CJH , Liefers G-J , Nortier HWR , Tollenaar RAEM , Mesker WE , Kroep JR 
Published: August 2014

Abstract
Background
Intra-tumoral stroma interacts with tumor cells and has a profound effect on tumor behavior. The tumor-stroma ratio (TSR) is of prognostic value in BC and other types of solid tumors. However, the predictive value of this parameter for achieving pathological complete response (pCR) after neoadjuvant chemotherapy is unknown.
Methods
We evaluated the relation between TSR and neoadjuvant treatment response in a retrospective cohort of 69 patients (pts) treated with various regimens of neoadjuvant chemotherapy at our institution who were diagnosed with BC between 1991 and 2007 and of whom radiological response was recorded. The percentage of intra-tumoral stroma was visually estimated on diagnostic sections from primary tumor tissue by two observers. The cut-off point between stroma-rich and stroma-poor tumors was set to 50% (as determined in previous investigations). These results were validated in a cohort from the NEOZOTAC trial: a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v. day 1) chemotherapy with or without zoledronic acid 4 mg i.v., q 3 weeks, 6 times in 250 pts with stage II/III, measurable, HER2-negative BC. Radiological response (complete or partial) was evaluated following RECIST 1.1 criteria. pCR was centrally revised and defined as absence of residual tumor cells in the original tumor bed.
Results
In the retrospective cohort (n = 69) 62.3% of the specimens were classified as stroma-rich. In univariate analysis TSR was significantly associated with radiological response (76.0% stroma-poor vs. 48.8% stroma-rich, P = 0.03). This finding persisted after multivariate analysis for T-status, N-status and ER-status (Odds Ratio [OR] 0.17, 95% C.I.: 0.04-0.78). In the validation set, in which 47.9% of the specimens were stroma-rich (211 cases evaluated), TSR did not predict for radiological response (79.5% stroma-poor vs. 79.2%, P = 0.96). However, when validation data were split on basis of ER-status, TSR was a significant and independent predictor for radiological response in ER-negative pts. (89.5% vs. 50%, P = 0.048, 95% C.I.: 0.01 - 0.98). In the validation set, TSR predicted for pCR with greater pCR rates in stroma-poor tumors (P = 0.03, 22.7% vs 10.3%). Final response results of the pilot and the enlarged sample size of all 250 pts of the validation set will be presented.
Conclusions
TSR might be a marker for radiological and pathological response to neoadjuvant chemotherapy, especially for the ER- tumor subgroup. Considering the simplicity and low cost of TSR assessment, it should be further evaluated and will be prospectively studied in the next neoadjuvant chemotherapy trial of the BOOG.
Contact information:
Dr. J.R. Kroep, M.D., Ph.D., Department of Medical Oncology, email:j.r.kroep@lumc.nl or T.J.A. Dekker, MSc. Department of Surgery and Medical Oncology, email: t.j.a.dekker@lumc.nl or LUMC datacenter, Department of Surgery, phone +31(0)71-5263500, fax +31(0)71-5266744, email: datacenter@lumc.nl, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-06-04.