Breast cancer is the most common cancer in women with more than 1 million new cases every year. Though curable at early stages, about 50 % of patients present with stage II or III tumours at diagnosis. The implementation of molecular diagnostic approaches would facilitate a more personalised therapeutic approach. However, there are very few biomarker tests established in the market necessitating high-throughput research towards biomarker discovery. The primary aim of the EU-funded RESPONSIFY (Genome-based biomarkers leading to validated molecular diagnostic tests for response prediction in breast cancer) project was to perform large-scale screening studies to identify and validate new biomarkers. Considerable effort went towards the discovery of genes capable of modulating the expression of the human epidermal growth factor receptor 2 (HER2). HER2 is one of the key genes associated with breast cancer development. Researchers used breast cancer cell lines and biobanked patient samples to perform whole-genome screening for biomarkers predictive of the response and resistance to anti-HER2 directed therapy. In addition, they evaluated serum markers for response to anti-angiogenic therapy and immunological alterations. This work led to the development of an mRNA-based immune predictive test ("ImmunoPredict") that can monitor changes in immunological status in breast cancer tissue. Scientists discovered that tumour-infiltrating lymphocytes are indicative of an active intra-tumoural immune environment and can be predictive for a response to anti-HER2 treatment. In contrast, PIK3CA mutations serve as a marker for reduced response to double anti-HER2 treatment. Screening for these two parameters has already been included in the German breast cancer guidelines. Additional biomarkers derived from screening approaches of RESPONSIFY have been transferred to a RT-PCR based test platform with promising results that merit further validation. Overall, assays and tools for a better patient stratification will not only improve breast cancer patient outcome, but should also offer socioeconomic benefits.
Biomarker, breast cancer, HER2, ImmunoPredict, lymphocytes, PIK3CA