Abstract 2769: Angiogenic profile in postmenopausal women is not associated with breast cancer risk

Abstract

Abstract Background: Angiogenesis is linked to breast cancer expansion and metastasis, but evidence for its role in the etiology of breast cancer, or as an early tumor marker is less clear. Women with pregnancy-induced hypertension and/or preeclampsia are at reduced risk of subsequent breast cancer, and the altered profile of angiogenic factors associated with these pregnancy complications may provide a clue as to the mechanism of this protection. Preeclampsia involves abnormal development of the maternal-placental vasculature and endothelial cell dysfunction resulting in high levels of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) and low levels of the angiogenic promoters, vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Subtle defects in placental function and angiogenic imbalances characteristic of preeclampsia can be present but undetected in uncomplicated pregnancies, although it is not known whether pregnancy-related imbalances between pro- and anti-antigenic factors persist post-partum. Material and Methods: To study the role of prediagnostic levels of circulating angiogenic factors in the development of breast cancer, we measured levels of VEGF, sFlt-1 and PlGF in baseline blood specimens obtained from 352 cases and an equal number of matched controls not using hormone supplements who were identified in a breast cancer study nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Screening Trial between 1996 and 2005. Angiogenic factors were measured at the Clinical & Epidemiologic Research Laboratory, Boston Children's Hospital using highly sensitive assays (sFlt-1and PlGF, Roche, Germany and VEGF, R&D Systems, Minneapolis, MN). Case-control differences in baseline characteristics and natural logarithm transformed levels of angiogenic factors were assessed by t tests or Wilcoxon rank sum tests. Quartile-specific odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models. Results: No differences were observed between cases and controls in mean levels of VEGF, sFlt-1 or PlGF (p>0.05). Similarly, OR analyses showed no significant associations with breast cancer for VEGF (HRQ4 v Q1 = 1.15, 95% CI = 0.75-1.76, ptrend = 0.72), sFlt-1(HRQ4 v Q1 = 0.78, 95% CI = 0.52-1.18, ptrend = 0.14), PlGF (HRQ4 v Q1 = 0.83, 95% CI = 0.53-1.29, ptrend = 0.68) or the ratio of (VEGF + PlGF) to sFlt-1 (HRQ4 v Q1 = 1.38, 95% CI = 0.90-2.11, ptrend = 0.34). Restricting analysis to cases diagnosed at least 2 years after baseline serum donation, a modest non-significant trend of increasing risk was suggested for VEGF (HRQ4 v Q1 = 1.23, 95% CI = 0.77-1.95, ptrend = 0.45). Conclusion: Overall, prediagnostic circulating levels of angiogenic factors are not significantly associated with postmenopausal breast cancer risk in the PLCO cohort. Citation Format: Roni T. Falk, Annetine C. Staff, Gary Bradwin, Ananth Karumanchi, Rebecca Troisi. Angiogenic profile in postmenopausal women is not associated with breast cancer risk. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2769. doi:10.1158/1538-7445.AM2015-2769