The Association between Vascular Endothelial Growth Factor (VEGF) Expression and Outcome in Invasive Breast Cancer Is Modified by Intrinsic Subtype: Results from the Nurses' Health Study.
Hannah Gilmore, Ying Liu, Rulla Tamimi, Stuart Schnitt, Graham Colditz, Laura Collins. Beth Israel Deaconess Medical Center, Boston; Washington University School of Medicine, St. Louis; Channing Laboratory, Brigham and Women's Hospital, Boston
Background: VEGF is important in breast carcinogenesis. In particular, VEGF up-regulation is associated with angiogenesis, tumor cell migration, invasion and resistance to apoptotic stimuli. While VEGF expression is correlated with several adverse prognostic factors including larger tumor size, higher grade, hormone receptor negativity, HER2 positivity, and lymph node metastasis, its role as an independent prognostic factor is controversial. Moreover, the relationship between VEGF expression and outcome in the breast cancer intrinsic subtypes is unclear.
Design: Tissue microarray (TMA) sections of invasive breast cancers from women enrolled in the Nurses' Health Study were immunostained for ER, PR, HER2, CK5/6, EGFR and VEGF. Cancers were categorized as luminal A (ER+/PR+, HER2- and grade 1 or 2); luminal B (ER+/PR+, HER2+ or ER+/PR+, HER2- and grade 3); HER2-type (ER-/PR-, HER2+); and basal-like (ER-/PR-/HER2- and EGFR or CK5/6+). Any VEGF staining of tumor cell cytoplasm was considered positive. Cox proportional models were used to estimate hazard ratios (HR) of overall and breast cancer-specific mortality (BSCM) and distant recurrence, adjusted for epidemiological, clinicopathological and related molecular factors, and diagnosis year.
Results: Overall, 72.5% of 1,788 breast cancers were VEGF+. VEGF expression was significantly correlated with tumor subtype (p<.0001), with higher frequency in luminal B, HER2-type and basal-like when compared with luminal A type. VEGF expression was not related to outcome when the whole population was analyzed. However, VEGF expression was significantly associated with increased risks for both distant recurrence (HR=1.5, 95%CI=1.1-2.1) and BCSM (HR=1.4, 95%CI=1.01-2.0) among luminal A cancers. There was no association between VEGF expression and outcome in women with luminal B, HER2-type or basal-like cancers. In the luminal A subset, VEGF expression was not associated with outcome in 902 patients who received hormonal therapy. However, among 262 patients treated without chemotherapy, VEGF expression was significantly associated with BCSM (HR=5.6, 95%CI=1.2-26.7).
Conclusions: An association between VEGF expression and outcome among women with breast cancer was seen only in luminal A tumors. Among this group, VEGF expression appears to be a prognostic marker but not a predictive factor for response to adjuvant hormonal therapy.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 10, Wednesday Afternoon