Molecular determinants of the inflammatory breast cancer phenotype. Oncology

Department of Internal Medicine, University of Michigan, Health System, USA.
Oncology (Williston Park, N.Y.) (Impact Factor: 2.32). 01/2009; 22(14):1556-61; discussion 1561, 1565-8, 1576.
Source: PubMed


Despite advances in multimodality treatment, inflammatory breast cancer (IBC) remains the most aggressive and lethal form of breast cancer. The use of primary human IBC cell lines and functional in vive xenograft cancer models have revealed characteristics innate to IBC thought to confer a strong metastatic potential and aggressive phenotype. Classic descriptive markers in IBC (e.g., estrogen and progesterone receptor status) often guide optimal therapy and aid in development of new diagnostic and prognostic technologies. Recent IBC research has examined two genes, RhoC GTPase and WISP3, which are concordantly altered in the majority of IBC tumors but not in non-IBC specimens. RhoC serves as a transforming oncogene by regulation of genes involved in the cell cycle, secretion of angiogenic factors, and activity of insulin-like growth factor (IGF). WISP3 functions as a tumor-suppressor gene by modulation of IGF activity and resultant inhibition of cell proliferation, growth, and angiogenesis. Continued research with molecular analysis technology is imperative in order to harness differential gene expression and fully discover a signature profile of IBC. The ultimate goal is to reveal the specific molecular determinants that underlie its aggressive phenotype so that we may accurately identify markers of disease, improve diagnostic tools and predictors of response to treatment, and even suggest targeted IBC-specific therapies that afford improved survival.

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    • "Although excellent rates of locoregional control are achievable 6, mortality is usually related to systemic recurrence. Because of the rarity of IBC and the inherent difficulty in obtaining tumor tissue from IBC patients, who may lack a tumor mass at presentation and typically receive upfront systemic chemotherapy, few studies have been performed to characterize its molecular biology 15-17. Understanding the distinct biologic and molecular behavior of IBC is likely to provide insight into carcinogenic mechanism(s) and aid discovery of novel targets for future treatment interventions. "
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    ABSTRACT: Background: Inflammatory breast cancer (IBC) is a rare, highly aggressive form of breast cancer. The mechanism of IBC carcinogenesis remains unknown. We sought to evaluate potential genetic risk factors for IBC and whether or not the IBC cell lines SUM149 and SUM190 demonstrated evidence of viral infection. Methods: We performed single nucleotide polymorphism (SNP) genotyping for 2 variants of the ribonuclease (RNase) L gene that have been correlated with the risk of prostate cancer due to a possible viral etiology. We evaluated dose-response to treatment with interferon-alpha (IFN-α); and assayed for evidence of the putative human mammary tumor virus (HMTV, which has been implicated in IBC) in SUM149 cells. A bioinformatic analysis was performed to evaluate expression of RNase L in IBC and non-IBC. Results: 2 of 2 IBC cell lines were homozygous for RNase L common missense variants 462 and 541; whereas 2 of 10 non-IBC cell lines were homozygous positive for the 462 variant (p= 0.09) and 0 of 10 non-IBC cell lines were homozygous positive for the 541 variant (p = 0.015). Our real-time polymerase chain reaction (RT-PCR) and Southern blot analysis for sequences of HMTV revealed no evidence of the putative viral genome. Conclusion: We discovered 2 SNPs in the RNase L gene that were homozygously present in IBC cell lines. The 462 variant was absent in non-IBC lines. Our discovery of these SNPs present in IBC cell lines suggests a possible biomarker for risk of IBC. We found no evidence of HMTV in SUM149 cells. A query of a panel of human IBC and non-IBC samples showed no difference in RNase L expression. Further studies of the RNase L 462 and 541 variants in IBC tissues are warranted to validate our in vitro findings.
    Journal of Cancer 01/2013; 4(2):104-16. DOI:10.7150/jca.5002 · 3.27 Impact Factor
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    • "While the characterization of IBC utilizing the IBCR categories provides a useful approach to an important disease, a more accurate and useful test in the standardization of the diagnosis may be provided by laboratory assays. A number of approaches, such as that described by Houchens and Merajver [19], are of great importance not only because of their potential to improve the diagnostic specificity for epidemiological studies but also the potential to lead to improved modes of treatment. It is important to realize that while IBC is relatively rare, the numbers approximate or exceed those of many other malignancies. "
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    ABSTRACT: The case definition for inflammatory breast cancer (IBC) is controversial. The American Joint Committee on Cancer defines IBC as redness, warmth and edema involving at least half the breast. The SEER program relies on a pathologic finding of dermal lymphatic invasion and recently added those with clinical involvement of more than 3/4 of the breast. We established a registry to collect information and specimens from IBC patients to clarify the epidemiology and biology of these tumors. The goals of this report are to suggest improvements regarding case definitions and provide data on the variety of presentations relevant to early diagnosis.
    Cancers 03/2010; 2(1):143-152. DOI:10.3390/cancers2010143
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    ABSTRACT: BACKGROUND: Inflammatory breast cancer is a rare, yet controversial, syndrome of invasive breast cancer. CASE REPORT: A female, Caucasian, 57-year-old patient presented at the emergency department with complaints suggestive of inflammatory breast cancer. CONCLUSIONS: Inflammatory breast cancer, besides the advances on its molecular profile, still remains a clinical entity difficult to diagnose, especially in the primary health care setting.
    Breast Care 12/2009; 4(6):397-399. DOI:10.1159/000261505 · 0.63 Impact Factor
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