2013
DOI: 10.1158/0008-5472.can-12-3349
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HER2 Drives Luminal Breast Cancer Stem Cells in the Absence of HER2 Amplification: Implications for Efficacy of Adjuvant Trastuzumab

Abstract: Although current breast cancer treatment guidelines limit the use of HER2 blocking agents to tumors with HER2 gene amplification, recent retrospective analyses suggest that a wider group of patients may benefit from this therapy. Utilizing breast cancer cell lines, mouse xenograft models and matched human primary and metastatic tissues, we demonstrate that HER2 is selectively expressed in and regulates self-renewal of the cancer stem cell population in ER+, HER2− luminal breast cancers. Although trastuzumab ha… Show more

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Cited by 217 publications
(181 citation statements)
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“…Therapies targeting stem-like breast cancer cells may best be administered in the adjuvant setting to obtain maximum clinical benefit (46), especially since residual tumors after conventional treatment show enrichment for tumor-initiating cells (14). We now show that driving PUMA expression with therapies such as Src inhibitors selectively targets αvβ3 + Slug + stem-like tumor cells.…”
Section: Slugmentioning
confidence: 73%
“…Therapies targeting stem-like breast cancer cells may best be administered in the adjuvant setting to obtain maximum clinical benefit (46), especially since residual tumors after conventional treatment show enrichment for tumor-initiating cells (14). We now show that driving PUMA expression with therapies such as Src inhibitors selectively targets αvβ3 + Slug + stem-like tumor cells.…”
Section: Slugmentioning
confidence: 73%
“…In contrast, age was not associated with increased risk of ER−/PR+ disease among Luminal B cases. This observation may be explained by findings using experimental models, that overexpression of HER2 supports aggressive tumor growth in luminal breast cancers 22.…”
Section: Discussionmentioning
confidence: 99%
“…23 Furthermore, bone metastases of breast cancer frequently overexpressed HER2 protein in the absence of ERBB2 gene amplification. 23 Therefore, disseminated CSCs or bone micrometastatic cells may be responsive to trastuzumab treatment regardless of HER2 status of the primary tumor. Thus, patients with HER2-negative tumors could benefit from trastuzumab in the adjuvant setting but not in the neoadjuvant or metastatic setting when pCR or PFS is the clinical end point.…”
Section: Discussionmentioning
confidence: 99%