This page provides study documentation for AS284. For description of the specimen results, see Specimen Results Description (open to public). Data sets of the specimen results are included in the existing WHI datasets located on the WHI Data on this site (sign in and a completed Data Distribution Agreement are required; see details on the Data site).
Investigator Names and Contact Information
Thomas Rohan [Thomas.Rohan@einstein.yu.edu]
Benign proliferative breast disease (BPBD) is a putative breast cancer precursor and knowledge of the etiology of BPBD may enhance our understanding of the origins of breast cancer. Obesity is an established risk factor for postmenopausal breast cancer and is associated with hyperinsulinemia, increased peripheral synthesis of estrogen and elevated levels of proinflammatory cytokines. In two recently completed WHI-OS ancillary studies of breast cancer, we observed significant and independent positive associations between insulin, estradiol, C-reactive protein (an inflammatory marker) and incident breast cancer, while adiponectin, an adipocyte-derived protein with insulin-sensitizing and anti-proliferative properties, was inversely associated with breast cancer risk. Given that BPBD is characterized by epithelial proliferation, and that each of the aforementioned obesity-related molecular pathways can lead to proliferation of breast tissue, we hypothesize that hyperinsulinemia, estrogen and inflammation might be etiologically relevant to BPBD. To test this hypothesis, we propose to prospectively investigate the associations of insulin, estradiol, C-reactive protein and adiponectin with the incidence of BPBD. Specifically, using incident cases of BPBD identified in the completed Benign Breast Disease ancillary study (AS-130), we propose to conduct a nested case-control investigation involving 700 cases of BPBD (297 with atypical hyperplasia and 403 without atypia) and 1,400 matched controls (women free of any benign breast disease).