P2-08-05: Use of Dynamic Contrast-Enhanced MR Imaging To Predict Pathological Response in Primary Breast Cancer.
Authors: Boni V , Pina LJ , Hernando B , Lopez-Vega JM , Calvo EG , Plazaola A , Morales S , Anton A , Sanchez-Gomez RM , Alvarez I , Illarramendi JJ , De Juan A , Martinez P , Llombart A , La Huerta A , Dominguez I , Garcia-Velloso MJ , Garcia-Gonzalez M , Lao Romera J , Puertolas T , Scherer S , Sabariz L , Garcia-Foncillas J 
Published: June 2012

Abstract
Purpose: To investigate the effect of bevacizumab infusion on vascular parameters assessed by dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging and to test their association with pathological response in primary breast cancer.
Materials and Methods: 73 patients (median age, 47 ys; age range, 29–70 ys) with biopsy-proven, previously untreated, primary breast cancer were recruited from October 2009 to November 2010 in this phase II, multicenter and non-randomized clinical trial. Patients (pts) received single infusion of bevacizumab (15 mg/kg) (C1) 3 weeks prior to the beginning of neoadjuvant chemotherapy consisting in 4 cycles of docetaxel (60 mg/mq), doxorubicin (50 mg/mq) and bevacizumab (15 mg/kg) every 21 days (C2-C5) following by surgery. All pts underwent DCE-MR imaging before and 14–21 days after C1. Quantitative and semiquantitative kinetic parameters were calculated at baseline and after C1, including the volume transfer constant (K(trans)), which primarily reflects the wash-in of the contrast agent, the backflow rate contrant (K(ep)), extracellular volume fraction (V(e)) and the initial area under the gadolinium concentration-time curve over 60 seconds (IAUGC(60)). Changes in the DCE-MRI kinetic parameters K(trans), K(ep), V(e) and IAUGC(60) were calculated and Wilcoxon test was used to assess significant effects induced by bevacizumab on kinetic parameters. Pathological response on surgical specimens after C5 was assessed according to Miller and Payne classification. Pts with tumor reduction &gt;30% were considered as responders (G3-G4-G5) whether tumor reduction &lt;30% were considered as no responders (G1-G2). DCE-MR imaging parameters and clinical-pathological characteristics were correlated with pathological response using Mann-Whitney test in univariate and logistic regression in multivariate analyses. Receiver operating curves (ROC) was used to define the best cut-off of the parameter found associated with pathological response.
Results: DCE-MRI was performed before (n=72) and after (n=71) C1. K(trans), K(ep), V(e) and IAUCG(60) values were significantly different at the baseline and after C1 (p&lt;0.01). Median changes were, respectively, −51, −101, −52.5 and −4.8. Fifty-two (74%) pts achieved response (G3-G4-G5) after C5 whether 18 (24%) were considered as no responder (G1-G2); for 3 (4%) patients Miller/Payne tumor evaluation was not available. At univariate analysis, negative estrogen receptor (ER) status and higher post-C1 K(ep) (p=.057) showed a trend toward an association with response. At multivariate analysis, only ER status remains a significant predictor of response (p= .04). Area under ROC curve for K(ep) was 0.65 (IC95% 0.05−0.8, p=.057)
Conclusion: Bevacizumab affects tumor vasculature, perfusion and permeability as showed by the significantly reduction in all kinetic vasculature parameters obtained in DCE-MR imaging after C1. However, in our population these changes were not associated with pathological response. On the other hand, backflow rate constant, K(ep), a perfusion-related parameter derived from DCE-MRI yielded after C1 major than 80, may be associated with higher pathological response with a specificity of 88% and sensitivity of 90%. Future studies are warranted to confirm these findings.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-08-05.