Trends for Inflammatory Breast Cancer: Is Survival Improving?

González-Angulo, Ana M.; Hennessy, Bryan T.; Broglio, Kristine; Meric‐Bernstam, Funda; Cristofanilli, Massimo; Giordano, Sharon H.; Buchholz, Thomas A.; Şahin, Ayşegül; Singletary, S. Eva; Buzdar, Aman U.; Hortobágyi, Gabriel N.

doi:10.1634/theoncologist.12-8-904

Cited by 109 publications

(67 citation statements)

References 23 publications

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Lehman

Laere

Golen

et al. 2012

Molecular Cancer Research

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With a 42% and 18% 5-and 10-year respective disease-free survival rate, inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer. IBC invades the dermal lymphatic vessels of the skin overlying the breast and as a consequence nearly all women have lymph node involvement and $1/3 have gross distant metastases at the time of diagnosis. One year after diagnosis $90% of patients have detectable metastases, making IBC a paradigm for lymphovascular invasion. Understanding the underlying mechanisms of the IBC metastatic phenotype is essential for new therapies. Work from our laboratory and others show distinct molecular differences between IBC and non-IBCs (nIBCs). Previously we showed that RhoC GTPase is a metastatic switch responsible for the invasive phenotype of IBC. In this study we integrate observations made in IBC patients with in vitro analysis. We show that the PI3K/Akt signaling pathway is crucial in IBC invasion. Key molecules involved in cytoskeletal control and cell motility are specifically upregulated in IBC patients compared with stage and cell-typeof-origin matched nIBCs patients. Distinctively, RhoC GTPase is a substrate for Akt1 and its phosphorylation is absolutely essential for IBC cell invasion. Further our data show that Akt3, not Akt1 has a role in IBC cell survival. Together our data show a unique and targetable pathway for IBC invasion and survival.

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Section: Introductionmentioning

confidence: 99%

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

Lehman

Laere

Golen

et al. 2012

Molecular Cancer Research

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“…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.…”

mentioning

confidence: 99%

“…A review of nearly 400 IBC patients treated at The University of Texas MD Anderson Cancer Center between 1974 and 2005 demonstrated that there has been no significant improvement in prognosis for patients with IBC over the past 30 years. 1 Many recent studies have focused on assessing the efficacy of chemotherapeutic regimens in IBC cells/patients where success had previously been observed only in the treatment of non-IBCs. 9,10 Some progress has been made in understanding the mechanisms underlying the invasive nature of IBC.…”

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confidence: 99%

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

et al. 2014

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Inflammatory breast cancer (IBC) is a rare and highly invasive type of breast cancer, and patients diagnosed with IBC often face a very poor prognosis. IBC is characterized by the lack of primary tumor formation and the rapid accumulation of cancerous epithelial cells in the dermal lymphatic vessels. Given that normal epithelial cells require attachment to the extracellular matrix (ECM) for survival, a comprehensive examination of the molecular mechanisms underlying IBC cell survival in the lymphatic vessels is of paramount importance to our understanding of IBC pathogenesis. Here we demonstrate that, in contrast to normal mammary epithelial cells, IBC cells evade ECM-detachment-induced apoptosis (anoikis). ErbB2 and EGFR knockdown in KPL-4 and SUM149 cells, respectively, causes decreased colony growth in soft agar and increased caspase activation following ECM detachment. ERK/MAPK signaling was found to operate downstream of ErbB2 and EGFR to protect cells from anoikis by facilitating the formation of a protein complex containing Bim-EL, LC8, and Beclin-1. This complex forms as a result of Bim-EL phosphorylation on serine 59, and thus Bim-EL cannot localize to the mitochondria and cause anoikis. These results reveal a novel mechanism that could be targeted with innovative therapeutics to induce anoikis in IBC cells.

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“…Significantly higher incidence of loco-regional recurrences are found in IBC patients compared to those with noninflammatory breast cancers. 2 Local recurrence has been linked to the presence of radioresistant Breast Cancer Stemlike Cells (BCSC). These cells, bearing the phenotype of CD44 high /CD24 low/-, resemble normal mammary stem cells in that they are capable of undergoing continuous self-renewal.…”

Section: Introductionmentioning

confidence: 99%

Long Term, Low Dose Genistein decreases Stem Cell Populations and Sensitizes Inflammatory Breast Cancer Cell Lines to Radiation

Sims‐Mourtada

Opdenaker²,

Davis³

et al. 2015

Cancer Stud Mol Med Open J

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Short CommunicationPage 60 ABSTRACTLocal recurrence in inflammatory breast cancer is common and is associated with poor prognosis. Recurrence is driven by a small population of radioresistant breast cancer cells that have stem-like properties. Previous studies have shown that high doses of the soy isoflavone genistein have a growth inhibitory effect on tumor cells, and may sensitize non-inflammatory breast cancer cells to radiation. The objective of this study was to determine the effect of genistein on the growth and radioresistance of inflammatory breast cancer cells. We show that short-term treatment of inflammatory cell lines IBC3 and SUM149 with genistein decreases cell proliferation and mammosphere forming ability only at micromolar doses, but had minimal effect on stem cell marker expression and radioresistance of these cells. However, long term treatment with a low dose (nM) of genistein, which may mimic dietary intake, decreased stem cell populations and mammosphere forming ability and increased radiation, induced cell death in these lines. We propose that dietary intake of genistein may be associated with improved local response to treatment in inflammatory breast cancer by decreasing growth of breast cancer stem cells.

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Trends for Inflammatory Breast Cancer: Is Survival Improving?

Cited by 109 publications

References 23 publications

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

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

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

Long Term, Low Dose Genistein decreases Stem Cell Populations and Sensitizes Inflammatory Breast Cancer Cell Lines to Radiation

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