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Genes Dis. 2018 May 12;5(2):77-106. doi: 10.1016/j.gendis.2018.05.001. eCollection 2018 Jun.

Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis.

Feng Y1,2, Spezia M2, Huang S1,2, Yuan C2,3, Zeng Z2,4, Zhang L2,5, Ji X2,5, Liu W1,2, Huang B2,4,6, Luo W2,7, Liu B1,2, Lei Y1,2, Du S2,8, Vuppalapati A2,8, Luu HH2, Haydon RC2, He TC2, Ren G1.

Author information

1
Chongqing Key Laboratory of Molecular Oncology and Epigenetics, Departments of General Surgery, Clinical Laboratory Medicine, Orthopaedic Surgery, Plastic Surgery and Burn, and Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
2
Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
3
Department of Biochemistry and Molecular Biology, China Three Gorges University School of Medicine, Yichang 443002, China.
4
Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
5
Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, The Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
6
Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
7
Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, The Affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing 401147, China.
8
Student Inquiry Research Program, Illinois Mathematics and Science Academy (IMSA), Aurora, IL 60506, USA.

Abstract

As the most commonly occurring cancer in women worldwide, breast cancer poses a formidable public health challenge on a global scale. Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast. While the risk factors associated with this cancer varies with respect to other cancers, genetic predisposition, most notably mutations in BRCA1 or BRCA2 gene, is an important causative factor for this malignancy. Breast cancers can begin in different areas of the breast, such as the ducts, the lobules, or the tissue in between. Within the large group of diverse breast carcinomas, there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites. It is important to distinguish between the various subtypes because they have different prognoses and treatment implications. As there are remarkable parallels between normal development and breast cancer progression at the molecular level, it has been postulated that breast cancer may be derived from mammary cancer stem cells. Normal breast development and mammary stem cells are regulated by several signaling pathways, such as estrogen receptors (ERs), HER2, and Wnt/β-catenin signaling pathways, which control stem cell proliferation, cell death, cell differentiation, and cell motility. Furthermore, emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer, especially for triple-negative breast cancer. This review provides a comprehensive survey of the molecular, cellular and genetic aspects of breast cancer.

KEYWORDS:

BRCA1/2; Breast cancer; Cancer stem cells; Estrogen receptors; HER2; Noncoding RNAs; Triple-negative breast cancer; Tumor heterogeneity

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