Inflammatory Breast Cancer: What We Know and What We Need to Learn

Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
The Oncologist (Impact Factor: 4.87). 05/2012; 17(7):891-9. DOI: 10.1634/theoncologist.2012-0039
Source: PubMed


We review the current status of multidisciplinary care for patients with inflammatory breast cancer (IBC) and discuss what further research is needed to advance the care of patients with this disease.
We performed a comprehensive review of the English-language literature on IBC through computerized literature searches.
Significant advances in imaging, including digital mammography, high-resolution ultrasonography with Doppler capabilities, magnetic resonance imaging, and positron emission tomography-computed tomography, have improved the diagnosis and staging of IBC. There are currently no established molecular criteria for distinguishing IBC from noninflammatory breast cancer. Such criteria would be helpful for the diagnosis and development of novel targeted therapies. Combinations of neoadjuvant systemic chemotherapy, surgery, and radiation therapy have led to an improved prognosis; however, the overall 5-year survival rate for patients with IBC remains very low (∼30%). Sentinel lymph node biopsy and skin-sparing mastectomy are not recommended for patients with IBC.
Optimal management of IBC requires close coordination among medical, surgical, and radiation oncologists, as well as radiologists and pathologists. There is a need to identify molecular changes that define the pathogenesis of IBC to enable eradication of IBC with the use of IBC-specific targeted therapies.

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    • "| DOI:10.1038/bjc.2015.115 1 systemic therapy . Post - operative radiation therapy is almost always indicated ( Yamauchi et al , 2012 ) . "
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    ABSTRACT: The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to encourage communication of the very best cancer research from laboratories and clinics in all countries. The breadth of its coverage, its editorial independence and it consistent high standards, have made BJC one of the world's premier general cancer journals. Its increasing popularity is reflected by a steadily rising impact factor.
    British Journal of Cancer 03/2015; 112(9). DOI:10.1038/bjc.2015.115 · 4.84 Impact Factor
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    • "This type of breast cancer is called ‘inflammatory’ because the breast often looks swollen and red, resembling an inflammatory condition (2). Although IBC accounts for only 2–5% of all breast cancers, IBC tumors show a poor prognosis with 40% five-years survival rate versus 87% for all breast cancers combined, making IBC a priority area for the development of new therapeutic strategies (3). IBC tumors display a triple negative breast cancer (TNBC) phenotype characterized by high chromosomal instability (CIN) and low levels of expression of estrogen receptor α (ERα), progesterone receptor (PR) and HER-2 tyrosine kinase receptor (4). "
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    ABSTRACT: Inflammatory breast cancer (IBC) is an angioinvasive and most aggressive type of advanced breast cancer characterized by rapid proliferation, chemoresistance, early metastatic development and poor prognosis. IBC tumors display a triple-negative breast cancer (TNBC) phenotype characterized by centrosome amplification, high grade of chromosomal instability (CIN) and low levels of expression of estrogen receptor α (ERα), progesterone receptor (PR) and HER-2 tyrosine kinase receptor. Since the TNBC cells lack these receptors necessary to promote tumor growth, common treatments such as endocrine therapy and molecular targeting of HER-2 receptor are ineffective for this subtype of breast cancer. To date, not a single targeted therapy has been approved for non-inflammatory and inflammatory TNBC tumors and combination of conventional cytotoxic chemotherapeutic agents remains the standard therapy. IBC tumors generally display activation of epithelial to mesenchymal transition (EMT) that is functionally linked to a CD44+/CD24-/Low stem-like phenotype. Development of EMT and consequent activation of stemness programming is responsible for invasion, tumor self-renewal and drug resistance leading to breast cancer progression, distant metastases and poor prognosis. In this study, we employed the luminal ER+ MCF-7 and the IBC SUM149PT breast cancer cell lines to establish the extent to which high grade of CIN and chemoresistance were mechanistically linked to the enrichment of CD44+/CD24low/- CSCs. Here, we demonstrate that SUM149PT cells displayed higher CIN than MCF-7 cells characterized by higher percentage of structural and numerical chromosomal aberrations. Moreover, centrosome amplification, cyclin E overexpression and phosphorylation of retinoblastoma (Rb) were restricted to the stem-like CD44+/CD24-/Low subpopulation isolated from SUM149PT cells. Significantly, CD44+/CD24-/Low CSCs displayed resistance to conventional chemotherapy but higher sensitivity to SU9516, a specific cyclin-dependent kinase 2 (Cdk2) inhibitor, demonstrating that aberrant activation of cyclin E/Cdk2 oncogenic signaling is essential for the maintenance and expansion of CD44+/CD24-/Low CSC subpopulation in IBC. In conclusion, our findings propose a novel therapeutic approach to restore chemosensitivity and delay recurrence of IBC tumors based on the combination of conventional chemotherapy with small molecule inhibitors of the Cdk2 cell cycle kinase.
    International Journal of Oncology 06/2014; 45(3). DOI:10.3892/ijo.2014.2523 · 3.03 Impact Factor
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    • "This was confirmed by studies showing similar expression levels of LIBC/WISP3, RhoC, and E-cadherin in IBC and non-IBC [15]. DNA microarrays studies showed gene expression differences between IBC and non-IBC, and results detected over-expression of Toll-like receptors (TLR) in IBC tissues versus non-IBC tissues [16]. TLR are highly expressed by myelomonocytic cells, including dendritic cells in response to microbial or viral infections [17]. "
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    ABSTRACT: Inflammatory breast cancer (IBC) is a highly metastatic and fatal form of breast cancer. In fact, IBC is characterized by specific morphological, phenotypic, and biological properties that distinguish it from non-IBC. The aggressive behavior of IBC being more common among young women and the low survival rate alarmed researchers to explore the disease biology. Despite the basic and translational studies needed to understand IBC disease biology and identify specific biomarkers, studies are limited by few available IBC cell lines, experimental models, and paucity of patient samples. Above all, in the last decade, researchers were able to identify new factors that may play a crucial role in IBC progression. Among identified factors are cytokines, chemokines, growth factors, and proteases. In addition, viral infection was also suggested to participate in the etiology of IBC disease. In this review, we present novel factors suggested by different studies to contribute to the etiology of IBC and the proposed new therapeutic insights.
    Journal of Advanced Research 06/2013; 5(5). DOI:10.1016/j.jare.2013.06.004
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