Triple‐Negative Breast Cancer: An Unmet Medical Need
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 poten...
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| Published in | The oncologist (Dayton, Ohio) Vol. 16; no. S1; pp. 1 - 11 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
Durham, NC, USA
AlphaMed Press
01.01.2011
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| Subjects | |
| Online Access | Get full text |
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| 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.
Triple‐negative breast cancer, characterized by tumors that do not express estrogen receptor, progesterone receptor, or HER‐2 genes, represents an important clinical challenge because these cancers do not respond to endocrine therapy or other available targeted agents. At present, there is not a clear, proven effective single agent that targets a defining vulnerability in triple‐negative breast cancer. However, there are a number of potential therapies currently under investigation that may eventually improve outcomes in these patients. |
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| AbstractList | 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. 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. 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. Triple‐negative breast cancer, characterized by tumors that do not express estrogen receptor, progesterone receptor, or HER‐2 genes, represents an important clinical challenge because these cancers do not respond to endocrine therapy or other available targeted agents. At present, there is not a clear, proven effective single agent that targets a defining vulnerability in triple‐negative breast cancer. However, there are a number of potential therapies currently under investigation that may eventually improve outcomes in these patients. |
| Author | Gianni, Luca Hudis, Clifford A. |
| Author_xml | – sequence: 1 givenname: Clifford A. surname: Hudis fullname: Hudis, Clifford A. email: hudisc@mskcc.org – sequence: 2 givenname: Luca surname: Gianni fullname: Gianni, Luca |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21278435$$D View this record in MEDLINE/PubMed |
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| Notes | Luca Gianni Disclosures: Clifford A. Hudis Onyx, Merck Research funding/contracted research Genentech None. Consultant/advisory role The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers. ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
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| Snippet | Triple‐negative breast cancer, characterized by tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or HER‐2 genes, represents an... Triple-negative breast cancer, characterized by tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or HER-2 genes, represents an... Abstract Triple-negative breast cancer, characterized by tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or HER-2 genes,... |
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| SubjectTerms | Androgen receptor Basal‐like breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Breast Neoplasms - therapy Chemotherapy Epidermal growth factor receptor Female Humans Poly(ADP‐ribose) polymerase Receptor, ErbB-2 - genetics Receptor, ErbB-2 - metabolism Receptors, Estrogen - metabolism Receptors, Progesterone - metabolism Triple‐negative breast cancer |
| Title | Triple‐Negative Breast Cancer: An Unmet Medical Need |
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