Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Mar 12;9(3):776.
doi: 10.3390/jcm9030776.

Breast Mammographic Density: Stromal Implications on Breast Cancer Detection and Therapy

Patricia Fernández-Nogueira  1 , Mario Mancino  2   3 , Gemma Fuster  2   4   5 , Paloma Bragado  6 , Miquel Prats de Puig  3   7 , Pere Gascón  2   8 , Francisco Javier Casado  2 , Neus Carbó  2
Affiliations
Review

Breast Mammographic Density: Stromal Implications on Breast Cancer Detection and Therapy

Patricia Fernández-Nogueira et al. J Clin Med. .

Abstract

Current evidences state clear that both normal development of breast tissue as well as its malignant progression need many-sided local and systemic communications between epithelial cells and stromal components. During development, the stroma, through remarkably regulated contextual signals, affects the fate of the different mammary cells regarding their specification and differentiation. Likewise, the stroma can generate tumour environments that facilitate the neoplastic growth of the breast carcinoma. Mammographic density has been described as a risk factor in the development of breast cancer and is ascribed to modifications in the composition of breast tissue, including both stromal and glandular compartments. Thus, stroma composition can dramatically affect the progression of breast cancer but also its early detection since it is mainly responsible for the differences in mammographic density among individuals. This review highlights both the pathological and biological evidences for a pivotal role of the breast stroma in mammographic density, with particular emphasis on dense and malignant stromas, their clinical meaning and potential therapeutic implications for breast cancer patients.

Keywords: ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), breast cancer detection; mammographic density; therapy resistance; tumour stroma.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Schematic representation of mammary gland organisation and representative mammograms of healthy breast tissue, including low (A1) and high (A2) mammographic density areas; and malignant lesions, including DCIS (B1) and IDC (B2). MD: mammographic density; DCIS: ductal carcinoma in situ; IDC: invasive ductal carcinoma.
Figure 2
Figure 2
Schematic model of breast epithelium and its stroma. Major changes in cell types and in extracellular matrix (ECM) between: (A) healthy mammary gland and (B) invasive breast carcinoma are depicted.
Figure 3
Figure 3
Paracrine crosstalk between fibroblasts and neighbouring epithelial cells. The abundance of stromal fibroblasts correlates with areas of high MD and stimulates epithelial cell proliferation by secreting copious soluble factors (A). The overstimulated epithelial cells, in turn, can undergo phenotypic changes and secrete fibroblast-activating factors. In these areas of high MD, the altered microenvironment can lead to the activation of fibroblasts into CAFs, which facilitate the growth and progression of the tumour cells. The secretion of growth factors, cytokines and proteases by CAFs establishes a positive feedback loop between both cell types which eventually leads to infiltration of immune cells and to chemoresistance. This pro-tumoural stroma also promotes angiogenesis, metastasis and therapy resistance (B).
See this image and copyright information in PMC

References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Duffy S.W., Morrish O.W.E., Allgood P.C., Black R., Gillan M.G.C., Willsher P., Cooke J., Duncan K.A., Michell M.J., Dobson H.M., et al. Mammographic density and breast cancer risk in breast screening assessment cases and women with a family history of breast cancer. Eur. J. Cancer. 2018;88:48–56. doi: 10.1016/j.ejca.2017.10.022. - DOI - PMC - PubMed
    1. Pellacani D., Tan S., Lefort S., Eaves C.J. Transcriptional regulation of normal human mammary cell heterogeneity and its perturbation in breast cancer. EMBO J. 2019;38:e100330. doi: 10.15252/embj.2018100330. - DOI - PMC - PubMed
    1. Bissell M.J., Hines W.C. Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat. Med. 2011;17:320–329. doi: 10.1038/nm.2328. - DOI - PMC - PubMed
    1. Saftlas A.F., Szklo M. Mammographic parenchymal patterns and breast cancer risk. Epidemiol. Rev. 1987;9:146–174. doi: 10.1093/oxfordjournals.epirev.a036300. - DOI - PubMed