Triple-Negative Breast Cancer: An Unmet Medical Need

Abstract

Triple-negative breast cancer, characterized by tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or HER-2 genes, represents an important clinical challenge because these cancers do not respond to endocrine therapy or other available targeted agents. The metastatic potential in triple-negative breast cancer is similar to that of other breast cancer subtypes, but these tumors are associated with a shorter median time to relapse and death. One important goal is therefore the identification of prognostic factors and markers to reliably select high and low risk subsets of patients with triple-negative disease for different treatment approaches of subtypes with differential responsiveness to specific agents. However, a reliable prognostic marker has been elusive, and markers have been inconsistently useful. For example, epidermal growth factor receptor (EGFR) has been studied, but there is still a lack of agreement on a standard assay or cutoff for EGFR expression levels with respect to prognosis. Similarly, because triple-negative status is sometimes used as a surrogate for basal-like breast cancer, specific basal markers have been explored. Indeed, trials designed to accrue patients with basal-like breast cancer using ER/PR and HER-2 negativity may provide only an approximation of the triple-negative population and are sometimes reanalyzed using more specific indicators like CK 5/6, EGFR status, and others, again marred by discordances. Chemotherapy remains the mainstay of treatment of triple-negative breast cancer, but important limitations still need to be overcome in the next few years if any significant clinical strides are to be made. Current treatment strategies for triple-negative disease include anthracyclines, taxanes, ixabepilone, platinum agents, and biologic agents. More recently, EGFR inhibition has been proposed as a therapeutic mechanism in triple-negative breast cancer, again with mixed results. Agents that target poly-(ADP-ribose) polymerase and androgen receptors have also been proposed in these patients or subsets of them, and ongoing trials should result in definitive guidance with respect to the value of these agents in triple-negative disease.Triple-negative breast cancer is clearly a distinct clinical subtype, from the perspective of both ER and HER-2 expression, but further subclassification is needed. At present, there is not a clear, proven effective single agent that targets a defining vulnerability in triple-negative breast cancer. This article will review the clinical problem of triple-negative disease, potential prognostic factors, demonstrated efficacy of currently available therapeutic options, and new potential therapies. The Oncologist 2011;16(suppl 1):1-11

Triple Negative Breast Cancer in People of North East India: Critical Insights Gained at a Regional Cancer Centre

“…Combination of imiparib and Gemcitabine provides significant clinical benefit. BRCA1 related TNBC appears to be particularly susceptible to chemotherapy involving Platinum based agents and Taxanes (Hudis and Gianni, 2011).…”

“…It lacks any specific targeted therapy at any at the current time. Combined chemotherapy is the present treatment modality (Hudis and Gianni, 2011).The emergence of novel agents (poly-ADP-ribose -polymerase-1 inhibitor) may improve the prognosis of TNBC but it is still at very preliminary stage of research (Ma et al, 2012). (So search for more predictive biomarkers for TNBC is the primary aim and goal of breast cancer research (Luo et al, 2010).…”

Emerging functional roles of nuclear receptors in breast cancer

“…Despite the success of endocrine therapies, there remain subgroups of women for whom available treatment offers little help. These include patients with ER+ breast tumors who develop endocrine treatment resistance (Dixon 2014), patients with estrogen receptornegative (ER−) breast cancers (Hudis & Gianni 2011) and cancers that recur in all age groups (EBCTCG 2005). Women in these subgroups currently face the challenge of living with advanced disease; therefore, there exists the need to develop rational treatments targeting these subgroups of breast cancer.…”

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“…The TNMBC has become one of the aggressive clinical cancers with poor prognosis among BC patients, being found in 15% to 20% of all BCs [63][64][65][66][67]. TNMBC is generally composed of heterogeneous group of cancers with high rate of proliferation and poorly differentiated cells [68].…”