Abstract 896: Serum-vascular endothelial growth factors (sVEGF) A and C have a potential as predictive tests for neoadjuvant bevacizumab in primary breast cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2014-10, Vol.74 (19_Supplement), p.896-896
• Main Authors: Linderholm, Barbro K., Minckwitz, Gϋnter von, Caramuta, Stefano, André, Fabrice, Sotiriou, Christos, Cerone, Maria A., Schwenkglenks, Matthias, Blank, Patricia, Denkert, Carsten, Gade, Stephan, Loibl, Sibylle
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2014-896

Background: Vascular endothelial growth factor (VEGF) is the major angiogenic factor in human cancer; VEGF-A is the most studied cytokine; VEGF-C is also involved in lymphatic development and both can act through binding to VEGFR2. Bevacizumab (Bev) is a humanized antibody directed towards VEGF with a modest effect in unselected HER2-negative breast cancer (BC). Patients & Methods: These VEGFs were determined in the randomized GeparQuinto trial investigating Bev as neoadjuvant treatment for HER2-negative BC (von Minckwitz et al N Eng J Med 2012). Patients were randomized to neoadjuvant chemotherapy with ECx4 and docetaxelx4 with or without concomitant Bev. VEGF-A, VEGF-C and VEGFR2 (VEGFs) were determined in serum samples prior to any treatment by use of commercial enzyme-linked immuno assays (Quantikine, R & D Systems, Minneapolis, USA). Serum levels of VEGF-A; -C and R2 were analyzed as dichotomized variables and correlated with pathological complete response (pCR, ypT0 ypN0) at surgery. Results: The VEGFs were determined in 830 (43%) trial participants of which 289 had triple negative (TN) and 541 hormone receptor positive (HR+) BC. The median age was 48 years (range 42-56), 81% had a ductal cancer and 44% were grade III. Median levels were 295.0 range 160-497 pg/mL for VEGF-A; 2102 range 1576-2588 pg/mL for VEGF-C; and 2328 range 1887-2913 pg/mL for VEGFR2, respectively. STEPP (subpopulation treatment effect pattern plot) analyses revealed a potential predictive value for all 3 VEGF's. In dichotomized analyses, TNBC patients with high VEGF-C had a higher chance of pCR with Bev in univariate analysis [interaction OR=4.4; p= 0.010] and multivariate analysis (interaction OR=6.5; p= 0.005) adjusted for age (≥ 50y vs. < 50y), histological type (ductal vs. lobular vs. others), grade (III vs. I-II), tumor stage (stage 4 vs. 1-3) and nodal status (node-negative vs. node positive). High VEGFR2 was correlated with pCR in univariate analysis [interaction OR=7.9; p= 0.017] whilst no effect was seen in multivariate analysis. HR+BC patients with high VEGF-A had an increased chance of pCR in univariate analysis [interaction OR=25.7; p< 0.001] and multivariate analysis [OR=29.4; p< 0.001]. A total 37.7% of the TNBC were classified as having high VEGFC and 31.2% obtained a pCR; 44.8% with Bev vs. 15.7% without Bev. A total of 89.3% of the TN patients were classified as “high VEGFR2” with a pCR rate of 31.4%; 39.5% with Bev vs. 23.9% without Bev. In the HR+ group, 41.6%