Skip to Main Content

An official website of the United States government

Angiogenic Profile and Risk of Breast Cancer in Postmenopausal Women

Principal Investigator
Name
Roni Falk
Degrees
-
Institution
NCI
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2010-0205
Initial CDAS Request Approval
Sep 24, 2010
Title
Angiogenic Profile and Risk of Breast Cancer in Postmenopausal Women
Summary
Evidence that an early pregnancy protects the mother against the development of breast cancer is well recognized; more recently, epidemiologic studies suggest that pregnancies complicated by preeclampsia, hypertension and small placental size may further lower this risk (1-3). While the biologic mechanism underlying the reduced breast cancer risk is not clear, the altered profile of angiogenic factors associated with these pregnancy complications may provide a clue. Specifically, levels of vascular endothelial growth factor (VEGF; also known as VEGF-A) and/or placental growth factor (PlGF) are low, while soluble fms-like tyrosine kinase-1(sFlt-1, also known as VEGF receptor 1) and soluble endoglin (sEng) are high in these conditions (4). Whether this low proangiogenic profile persists in women with a history of these pregnancy complications is not known. Angiogenesis is linked to breast cancer prognosis (5), but evidence for its role in the etiology of breast cancer, or as an early tumor marker is less clear. Few studies have studied circulating angiogenic factors in relation to breast cancer risk (6-8), and those that have, compared levels in samples collected after diagnosis of breast cancer to healthy controls.
Aims

We propose to evaluate the hypothesis that a persistent anti-angiogenic profile in healthy postmenopausal women reduces the risk of postmenopausal breast cancer risk using prospectively collected samples in the PLCO trial. Specifically we aim to 1) evaluate the association between serum VEGF, sFlt1, sEng and PlGF and postmenopausal breast cancer risk. We hypothesize that women with higher levels of the proangiogenic factors VEGF and PlGF will have higher risk, and women with higher levels of the antiangiogenic factors (sFlt-1 and sEng) will have a lower risk of breast cancer. For women with available pathology information, we will also evaluate the whether these risks vary by breast tumor characteristics, including estrogen and progesterone receptor status, ki67 result, oncotype dx results, stage and nodal status; 2) to determine whether the association between these factors and breast cancer risk, is independent of breast cancer risk factors thought to operate via a hormonal pathway. We hypothesize that the angiogenic pathway explains at least part of the effect of these risk factors, and adjustment for hormone-related breast cancer factors will attenuate the angiogenic risk estimates and 3) assess whether circulating levels of angiogenic factors confer breast cancer risk independent of sex steroid hormones.

Collaborators

Roni Falk (HREB, DCEG)
Barry Graubard (BB, DCEG)
Rebecca Troisi (OD, DCEG)

Related Publications