Abstract
HER2 receptor is overexpressed approximately in 20 % of human breast cancer (BC) and is a poor prognostic factor. Although therapies targeting this receptor have improved the prognosis of this cancer, up to 62 % patients treated with these drugs experiment progression during the first year of treatment. Some molecular mechanisms have been proposed to be responsible for this resistance, such as activation of alternative signaling pathways (through ERBB receptors and non-ERBB receptors or increased expression of ligands and alterations in HER2 signaling components). In this article, we will review the influence of genetic markers in non-HER2 signaling pathways investigated to date as cause of resistance to HER2-targeted drugs in HER2-positive BC patients. GRB7, included in the 17q12 amplicon, has been associated to poor prognosis in BC patients. Biomarkers like EPHAR and SRC, have demonstrated clinical relevance and prognostic value in HER2-positive BC patients. Non-invasive biomarkers, such as elevated IGF1 serum levels have been revealed as interesting biomarkers to be considered as predictors of trastuzumab clinical outcomes in BC patients. However, the prognostic value of most of the biomarkers investigated to date, such as HER3, IGF1R, PIK3CA, or AKT1 cannot be fully established yet, since results have not been conclusive.
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Abbreviations
- BC:
-
Breast cancer
- CBR:
-
Clinical benefit rate
- CR:
-
Complete response
- ER:
-
Estrogen receptor
- LABC:
-
Locally advance breast cancer
- MBC:
-
Metastatic breast cancer
- hR:
-
Hormonal receptor
- NS:
-
Non-significant
- pCR:
-
Pathologic complete response
- PFS:
-
Progression-free survival
- RFS:
-
Relapse-free survival
- RR:
-
Response rate
- OR:
-
Odds ratio
- ORR:
-
Overall response rate
- OS:
-
Overall survival
- TFR:
-
Trastuzumab failure rate
- TTP:
-
Time to progression
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Acknowledgments
The results of this investigation are part of the doctoral thesis presented by Adela Madrid-Paredes at the University of Granada.
Funding
This work was partly supported by a contract for Marisa Cañadas-Garre (Técnicos de Apoyo Subprogram. CA12/00097) from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad.
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The authors declare that there is not conflict of interest that could be perceived as prejudicing the impartiality of the research reported and there is not any competing financial interest in relation to the work described in this article.
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Madrid-Paredes, A., Cañadas-Garre, M., Sánchez-Pozo, A. et al. Non-HER2 signaling pathways activated in resistance to anti-HER2 therapy in breast cancer. Breast Cancer Res Treat 153, 493–505 (2015). https://doi.org/10.1007/s10549-015-3578-x
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DOI: https://doi.org/10.1007/s10549-015-3578-x