Challenging Clinical Scenarios: Treatment of Patients With Triple-Negative or Basal-Like Metastatic Breast Cancer

Greenberg, Sally; Rugo, Hope S.

doi:10.3816/cbc.2010.s.009

Cited by 13 publications

(9 citation statements)

References 74 publications

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“…Geminin and c-Abl mRNAs levels are low in normal tissue (n = 5) and luminal A tumors (n = 7), moderate in Her2 + tumors (n = 11), and high in luminal B (n = 9) and triple negative breast cancer (TNBC) [38], [39] (n = 7) tumors (Fig. 5A).…”

Section: Resultsmentioning

confidence: 99%

Geminin Overexpression Promotes Imatinib Sensitive Breast Cancer: A Novel Treatment Approach for Aggressive Breast Cancers, Including a Subset of Triple Negative

et al. 2014

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Breast cancer is the second leading cause of cancer-related deaths in women. Triple negative breast cancer (TNBC) is an aggressive subtype that affects 10–25% mostly African American women. TNBC has the poorest prognosis of all subtypes with rapid progression leading to mortality in younger patients. So far, there is no targeted treatment for TNBC. To that end, here we show that c-Abl is one of several tyrosine kinases that phosphorylate and activate geminin’s ability to promote TNBC. Analysis of >800 breast tumor samples showed that geminin is overexpressed in ∼50% of all tumors. Although c-Abl is overexpressed in ∼90% of all tumors, it is only nuclear in geminin overexpressing tumors. In geminin-negative tumors, c-Abl is only cytoplasmic. Inhibiting c-Abl expression or activity (using imatinib or nilotinib) prevented geminin Y150 phosphorylation, inactivated the protein, and most importantly converted overexpressed geminin from an oncogene to an apoptosis inducer. In pre-clinical orthotopic breast tumor models, geminin-overexpressing cells developed aneuploid and invasive tumors, which were suppressed when c-Abl expression was blocked. Moreover, established geminin overexpressing orthotopic tumors regressed when treated with imatinib or nilotinib. Our studies support imatinib/nilotonib as a novel treatment option for patients with aggressive breast cancer (including a subset of TNBCs)-overexpressing geminin and nuclear c-Abl.

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Section: Resultsmentioning

confidence: 99%

Geminin Overexpression Promotes Imatinib Sensitive Breast Cancer: A Novel Treatment Approach for Aggressive Breast Cancers, Including a Subset of Triple Negative

et al. 2014

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“…1,19–22 Hence, we examined survival estimates by race/ethnicity for several biologic marker types currently in common use based on a combination of ER, PR and HER2 markers, including ER/PR positive and negative, non-TN and TN, and luminal A/B and basal types. Survival estimates were marginally worse for AA women irrespective of the aforementioned types, suggesting that risk associated with these types is not race specific.…”

Section: Discussionmentioning

confidence: 99%

Race and the Prognostic Influence of p53 in Women with Breast Cancer

Dookeran¹,

Dignam

Holloway

et al. 2012

Ann Surg Oncol

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“…Bevacizumab, a humanized anti-VEGF monoclonal antibody, has been the most studied and has demonstrated activity when added to chemotherapy in both neoadjuvant and metastatic first/second-line treatments of TNBC (see Table 3) [110,[130][131][132][133][134][135]. Subset analyses have suggested a greater degree of efficacy in TNBC patients, but it is not clear that this is biologically driven or due to a higher event rate in this population.…”

Section: Angiogenesis Inhibitorsmentioning

confidence: 99%

Molecular heterogeneity of triple-negative breast cancer and its clinical implications

Irshad

Ellis

Tutt

2011

Current Opinion in Oncology

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Challenging Clinical Scenarios: Treatment of Patients With Triple-Negative or Basal-Like Metastatic Breast Cancer

Cited by 13 publications

References 74 publications

Geminin Overexpression Promotes Imatinib Sensitive Breast Cancer: A Novel Treatment Approach for Aggressive Breast Cancers, Including a Subset of Triple Negative

Geminin Overexpression Promotes Imatinib Sensitive Breast Cancer: A Novel Treatment Approach for Aggressive Breast Cancers, Including a Subset of Triple Negative

Race and the Prognostic Influence of p53 in Women with Breast Cancer

Molecular heterogeneity of triple-negative breast cancer and its clinical implications

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