The Molecular Biology of Inflammatory Breast Cancer
Inflammatory breast cancer (IBC) is a rare and clinically more aggressive type of breast cancer. This type of breast cancer is called “inflammatory” because the breast often appears to be swollen, reddened, or “inflamed.” Some studies have demonstrated an association between familial history of breast cancer and IBC; however, additional studies are required to demonstrate this. IBC is classified as breast cancer at stage IIIB or IV. Some signaling pathways undoubtedly provide novel therapeutic targets for developing IBC inhibitors. By means of a cell line study, the loss has been identified of Wnt signaling pathway-induced protein 3 (WISP3/CCN6; LIBC [Lost in Inflammatory Breast Cancer]). Microarray analysis in IBC compared in noninflammatory tumors has demonstrated a signature of IBC that includes genes involved in IGF signaling, which we will discuss later in the section on microarrays and genomic signatures in IBC. Overexpression of epidermal growth factor receptors (ErbB) is very common in IBC. In another study, the expression and correlation was evaluated of the protein caveolin-1, which is a structural protein of the IBC-cell membrane caveolar microdomains (also described in breast cancer cell lines) and not in the cells of noninflammatory mammary cancer tumors. A protein that has demonstrated to possess tumor suppressor properties in breast cancer is E-cadherin; likewise, it has been demonstrated that it is found to be overexpressed in IBC, allowing the formation of lymphovascular emboli, which offers cytoprotector and resistance mechanisms to the chemotherapy of IBC cells. The genomic profile of IBC and of noninflammatory breast tumors stratified according to hormonal receptor state and HER2.
KeywordsBreast Cancer Epidermal Growth Factor Receptor Inflammatory Breast Cancer Epidermal Growth Factor Receptor Extracellular Regulatory Kinase
- 1.Merajver SD, Sabel MS. Inflammatory breast cancer. In: Harris JR, Lippman ME, Morrow M, Osborne CK, editors. Diseases of the breast. 3rd ed. Philadelphia: Lippincott Williams and Wilkins; 2004.Google Scholar
- 3.Hamidullah, Changkija B, Konwar R. Role of interleukin-10 in breast cancer. Breast Cancer Res Treat. 2012 May;133(1):11–21.Google Scholar
- 4.Xie G, Yao Q, Liu Y, Du S, Liu A, Guo Z, Sun A, Ruan J, Chen L, Ye C, Yuan Y. IL-6-induced epithelial-mesenchymal transition promotes the generation of breast cancer stem-like cells analogous to mammosphere cultures. Int J Oncol. 2011. doi: 10.3892/ijo.2011.1275.
- 8.Bonafè M, Storci G, Franceschi C. Inflamm-aging of the stem cell niche: breast cancer as a paradigmatic example: breakdown of the multi-shell cytokine network fuels cancer in aged people. Bioessays. 2011. doi: 10.1002/bies.201100104.
- 9.Doyle SL, Donohoe CL, Lysaght J, Reynolds JV. Visceral obesity, metabolic syndrome, insulin resistance and cancer. Proc Nutr Soc. 2011;3:1–9.Google Scholar
- 18.Bekhouche I, Finetti P, Adelaïde J, Ferrari A, TarpinC, Charafe-Jauffret E, Charpin C, Houvenaeghel G, Jacquemier J, Bidaut G, Birnbaum D, Viens P, Chaffanet M, Bertucci F. High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes (abstract). PLoS One. 2011;6(2):e16950.PubMedCrossRefGoogle Scholar
- 20.Sezgin C, Gokmen E, Kapkac M, Zekioglu O, Esassolak M, Karabulut B, Sanli UA, Uslu R. p53 protein accumulation and presence of visceral metastasis are independent prognostic factors for survival in patients with metastatic inflammatory breast carcinoma. Med Princ Pract. 2011;20(2):159–64. Epub 2011 Jan 20.PubMedCrossRefGoogle Scholar
- 32.Iwamoto T, Bianchini G, Qi Y, Cristofanilli M, Lucci A, Woodward WA, Reuben JM, Matsuoka J, Gong Y, Krishnamurthy S, Valero V, Hortobagyi GN, Robertson F, Symmans WF, Pusztai L, Ueno NT. Different gene expressions are associated with the different molecular subtypes of inflammatory breast cancer. Breast Cancer Res Treat. 2011;125(3):785–95. Epub 2010 Dec 9.PubMedCrossRefGoogle Scholar
- 43.de Souza CH M, Toledo-Piza E, Amorin R, Barboza A, Tobias KM. Inflammatory mammary carcinoma in 12 dogs: clinical features, cyclooxygenase-2 expression, and response to piroxicam treatment. Can Vet J. 2009;50:506–10.Google Scholar