Improved breast cancer therapy (I-BCT-1) in the neoadjuvant and metastatic setting is a phase 2 clinical trial protocol studying biological rationale for the optimal selection of the treatment regimens.
High-throughput methods in molecular biology have revealed considerable alterations in the breast cancer genome, transcriptome and proteome with extensive heterogeneity between tumors, potentially explaining the large variation in response to treatment. Classification of breast cancer can be based on such molecular alterations, and have shown to be of clinical relevance. However, studies on how genome-wide mRNA/miRNA expression, copy number alterations (CNAs) and DNA methylation, in addition to the detection of circulating tumor DNA could be used to improve prognostication and aid in therapy decision are highly needed. This project includes a protocol for a phase II clinical trial where patients will be randomized to treatment with standard anthracycline- and taxane containing chemotherapy with or without the addition of carboplatin. The study aims to include patients with large primary breast cancer (150 patients) and patients with metastatic disease (60 patients). Essential for the study is the mandatory tissue samples for comprehensive molecular analyses to identify markers of response.
The primary aim of the study is to investigate the relationship between response to DNA targeted treatment and genomic tumor alterations in patients with primary or metastatic breast cancer, to define markers identifying a responding patient sub-population. The following main hypotheses will be tested:
- Genomic complex alterations may be used as predictor for response to DNA damaging agents
- Intrinsic subtypes in concert with proteomic and metabolomic information, may be used for therapeutic target identification and selection of specific therapies
- BRCA-like profiles of CNAs in tumors may be used for identification of DNA directed therapy
- The level of cell-free circulating tumor DNA with alterations specific to the primary tumor can be used for monitoring of therapy
PI: Olav Engebråten, Oslo University Hospital.