Investigators from the National Cancer Institute (NCI) identified changes in stromal breast tissue, called stromal disruption, that may help to identify women with a higher risk of developing breast cancer, according to study findings published in the Journal of the National Cancer Institute. Women with healthy breast tissue as well as those with benign breast disease all showed an increased risk for aggressive breast cancer with the presence of stromal disruption.
The study authors, led by Mustapha Abubakar, MD, PhD, of the Division of Cancer Epidemiology and Genetics at the NCI, noted that insights into stromal disruption may help to inform cancer prevention and treatment strategies targeting the role of the active stroma in the tumor microenvironment, as stromal disruption is relatively inexpensive to assess and adopt widely.
Study Methods and Results
Study investigators used machine-learning algorithms to identify changes in the stroma of 4,023 samples from healthy breast tissue, 974 biopsies of women with benign breast disease as a nested case-control study, and 4,223 biopsies of tissue from women with invasive breast cancer. The researchers characterized stromal disruption as a morphologic measure of an altered extracellular matrix and increased immune response processes in breast tissue.
Strong associations were found between greater stromal disruption and other epidemiologic risk factors for aggressive breast cancer prior to the development of breast cancer. This suggests that these risk factors plus stromal disruption may act on a common stromal tissue pathway.
Women with benign breast disease who had substantial stromal disruption showed about a fourfold increase in risk for developing high-grade breast cancer with a shorter time to breast cancer diagnosis from benign breast disease by about 3 years. Among women with invasive breast cancer, stromal disruption was associated with more aggressive tumor phenotypes regardless of histology, and women with estrogen receptor–positive breast cancer had especially poor prognoses with the presence of stromal disruption. Immunologic analysis showed that stromal disruption was associated with greater expression of innate, adaptive, immunoregulatory, immune escape, endothelial, and myofibroblast markers.
The study authors noted that chronic inflammation and wound healing could also play a role in stromal disruption. Thus, further studies are needed to determine whether stromal disruption prevention is an effective method of reducing the risk for developing aggressive breast cancer.
Disclosure: For full disclosures of the study authors, visit academicoup.com.
