BoneKEy Reports | BoneKEy Watch

Early treatment with Herceptin could benefit a wider group of women with breast cancer


HER2-blockers, notably trastuzumab (Herceptin), are currently reserved for women whose tumors show amplification of HER2; Ithimakin et al. examined whether trastuzumab could have a beneficial impact on metastasis caused by cancer stem cells that do not have amplified copies of the gene.

They first showed that expression of the cancer stem cell (CSC) marker aldehyde dehydrogenase correlated positively with HER2 expression. When HER2+ and HER2− cells were compared in tumor initiation experiments in nonobese diabetic/severe combined immunodeficient mice, tumor formation was significantly faster with HER2+ cells. In vitro studies using luminal breast cancer cells then demonstrated that trastuzumab, the HER2-blocking antibody, significantly reduced the number of CSCs present.

In vivo studies then showed that trastuzumab did not affect the growth of established mouse xenografts initiated by injection of luminal breast cancer cells; co-injection of the CSCs with trastuzumab did block tumor formation. Human bone metastases and bone xenografts initiated in mice had higher levels of HER2 expression, not due to amplification of the gene, but mediated by the RANK ligand within the bone microenvironment.

Editor’s comment: This study has important clinical implications for the adjuvant use of trastuzumab. The results obtained show that a much larger group of women with breast cancer may benefit from early treatment with trastuzumab, as this antibody can target and limit CSCs that do not show the classical HER2 gene amplification.

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