Abstract SY25-02: Double-edged “soil”: Stromal microenvironment in breast cancer development

• Published in: Cancer research (Chicago, Ill.) Ill.), 2022-06, Vol.82 (12_Supplement), p.SY25-02-SY25-02
• Main Authors: Abubakar, Mustapha, Fan, Shaoqi, Duggan, Maire A., Pfeiffer, Ruth M., Lawrence, Scott, Richert-Boe, Kathryn, Glass, Andrew, Kimes, Teresa M., Figueroa, Jonine D., Rohan, Thomas E., Gierach, Gretchen L.
• Format: Article
• Language: English
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2022-SY25-02

Double-edged “Soil”: Stromal Microenvironment in Breast Cancer Development Mustapha Abubakar, MD, PhD1; Shaoqi Fan, MPH1; Máire A. Duggan, MD, FRCPC2; Ruth M. Pfeiffer, PhD1; Scott Lawrence, M.S.3; Kathryn Richert-Boe, MD4; Andrew G. Glass, MD4; Teresa M. Kimes, MS4; Jonine D. Figueroa, PhD, MPH5; Thomas E. Rohan, MBBS, PhD6; Gretchen L. Gierach, PhD, MPH1. Affiliations 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health (NIH), USA2Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, T2N2Y9, Alberta, Canada3Molecular and Digital Pathology Laboratory, Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD 217024Kaiser Permanente Center for Health Research, Portland, Oregon 5Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Scotland, UK6Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, 10461 Deceased Background Over a century after Paget’s postulation of the “seed” and “soil” hypothesis of breast cancer metastasis, understanding of the role of the “soil” (i.e., local or distant stromal microenvironment) in supporting and promoting the growth and dissemination of “seed” tumor cells has increased considerably. However, the role of the stromal microenvironment in early stages of breast cancer development, including tissue origins of etiologic heterogeneity, remains poorly understood. To date, the prevailing model of breast cancer development involves a linear sequence of epithelial changes that begin from normal epithelium, progress to flat epithelial atypia (FEA), develop into atypical ductal hyperplasia, transform into ductal carcinoma in situ (DCIS), and culminate in the emergence of invasive breast cancer. An alternative model proposes the evolution of FEA from usual ductal hyperplasia, but this is not supported by a clear genetic link between the two. Notably, established models of breast cancer development are predicated almost exclusively on sequences of epithelial changes. Although recent efforts have shed light on the significance of stromal microenvironment in DCIS to invasive breast cancer progression, its role in breast cancer development following benign breast disease (BBD) is less well-studied. MethodsIn this case-control study, nested within a cohort of 15,395 BBD patients from Kaiser Permanente Northwest (1970-2012) who were followed for subse