Update on inflammatory breast cancer

Abstract

52 bFGF = basic fibroblast growth factor; ER = estrogen receptor; IBC = inflammatory breast cancer; IL = interleukin; LABC = locally advanced breast cancer; RT-PCR = reverse transcriptase-polymerase chain reaction; VEGF = vascular endothelial growth factor. Breast Cancer Research Vol 7 No 2 Lerebours et al. AbstractInflammatory breast cancer (IBC) is both the least frequent and the most severe form of epithelial breast cancer. The diagnosis is based on clinical inflammatory signs and is reinforced by pathological findings. Significant progress has been made in the management of IBC in the past 20 years. Yet survival among IBC patients is still only one-half that among patients with non-IBC. Identification of the molecular determinants of IBC would probably lead to more specific treatments and to improved survival. In the present article we review recent advances in the molecular pathogenesis of IBC. A more comprehensive view will probably be obtained by pan-genomic analysis of human IBC samples, and by functional in vitro and in vivo assays. These approaches may offer better patient outcome in the near future. IntroductionInflammatory breast cancer (IBC) is diagnosed on the basis of signs of rapid progression, such as localized or generalized breast induration, redness and edema [1]. IBC accounts for less than 5% of all diagnosed breast cancers [2].IBC is the most lethal form of primary breast cancer [2]. Surgery and/or radiation therapy offers a 5-year survival rate of less than 15% [1]. The current consensus treatment is first-line chemotherapy with an anthracyclinebased regimen, possibly combined with a taxane, followed by mastectomy and axillary lymph node dissection for responders, locoregional radiotherapy and, when appropriate, hormone therapy [3,4]. The benefits of dose-intensive therapy and bone marrow transplantation are not clearly established in this setting [5,6]. Maintenance adjuvant chemotherapy and new therapeutic approaches are under study. Despite multimodality treatments, the prognosis remains poor, with a 3-year survival rate of only about 40%, compared with 85% among patients with non-IBC [2,3]. These survival data have hardly improved in the past 5 years [3,7].The main issue in IBC is to identify the specific pattern of genetic changes accounting for this particular phenotype and aggressiveness, so that we can develop more effective targeted treatments. Little is known of these biological and molecular mechanisms, for several reasons. First, IBC is rare. Second, the small size of diagnostic samples may have hindered past molecular studies. Third, because of their similar treatment, IBC is rarely studied separately from other forms of locally advanced breast cancer (LABC), despite differences in age-specific incidence rates, clinical presentation, histology, hormone receptor status and, finally, prognosis [8][9][10][11]. The molecular mechanisms underlying these distinct clinicopathological entities are likely to differ, and should thus be studied comparatively.It is highly probable that the...

Regulation of Inflammatory Breast Cancer Cell Invasion through Akt1/PKBα Phosphorylation of RhoC GTPase

“…Despite significant improvements in the disease-free survival rates of non-IBC (nIBC) patients, IBC patient survival rates remain low, with a 5-year disease-free survival rate of less than 40%, in comparison to the $90% of nIBC (4,(7)(8)(9). The poor prognosis is due to infiltration of tumor emboli that metastasize within the dermal lymphatic vessels of the skin overlying the breast (3,4).…”

Anoikis evasion in inflammatory breast cancer cells is mediated by Bim-EL sequestration

“…The 5-year survival rate for patients with IBC is o40%, while the 5-year survival rate of all other breast cancers combined is approximately 90%. [1][2][3][4] This poor prognosis can be attributed to a number of factors, including the propensity for misdiagnosis of the disease due to its unique clinical presentation. [5][6][7] In contrast to most breast cancers, IBC is characterized by the lack of discernible primary tumor formation and the accumulation of cancerous epithelial cells in the dermal lymphatic vessels.…”

Distinct molecular phenotype of inflammatory breast cancer compared to non-inflammatory breast cancer using Affymetrix-based genome-wide gene-expression analysis

“…It is a distinct clinical subtype of locally advanced breast cancer (LABC), with a particularly aggressive behaviour and poor prognosis (median 3-year survival of about 40%). Clinically, IBC typically presents with rapidly progressive breast erythema, warmth, oedema and induration, often without palpable underlying tumour mass (Kleer et al, 2000;Lerebours et al, 2005;Dirix et al, 2006). Tumour emboli in dermal lymphatics may be apparent on skin biopsy, but in the absence of clinical findings do not indicate IBC (Kleer et al, 2000;Low et al, 2004;Lerebours et al, 2005;Dirix et al, 2006).…”