Identifying the challenges of biomarkers that predict response to HER2-directed therapies

The identification of the human epidermal growth factor receptor 2 (HER2) as a targetable marker of adverse prognosis along with the development of HER2-directed therapies, have significantly improved outcomes for women with HER2-overexpressing breast cancers. However, both resistance to treatment and treatment-related toxicities have contributed to a less-than-ideal effect even as we have access to an increasing number of HER2-directed therapies making treatment selection potentially complex. Therefore, identifying biomarkers that predict response and/or resistance to specific HER2-directed therapies is an attractive clinical aim. In doing so, it is hoped that patients may be spared ineffective treatments and unnecessary toxicity, while maximizing benefit from available therapies. However, distinguishing and quantifying relevant markers have been significant obstacles. Both genomic and proteomic strategies have been employed, yet discrepancies have arisen and no clearly predictive marker has been identified beyond HER2 itself. Recent data may change this situation and possibly provide guidance for future research.