Advances in the Treatment of Breast Cancer

Abstract

The biennial Madrid Breast Cancer Conference has become one of the leading summer meetings dedicated to reviewing and discussing the most relevant advances in breast cancer research. Seminal, practice-changing results have been presented and reviewed in different sessions and symposia, embracing various aspects from molecular genetics to advances in imaging, staging and treatment in the different settings of the disease. Oncologists need improved tools to select treatments for individual patients. Most cancer treatments benefit only a minority of the patients to whom they are administered. Prognostic and predictive factors play important roles in the treatment of breast cancer, but very few such factors are used in clinical practice and prognostic relevance remains unclear. The ability to predict which patients are most likely to benefit from a given treatment would not only save patients from unnecessary toxicity and inconvenience, but might also facilitate their receiving drugs that are more likely to help. The current standard tools used to test new therapies in early breast cancer are Phase III randomized adjuvant trials. Such trials are large, expensive and take years to achieve their outcome. Neoadjuvant or primary systemic therapy (PST) trials might offer the eventual possibility of a more rapid and less resource-demanding alternative, at least for some therapies, if short-term surrogate clinical, pathologic or biologic end points could be identified that might predict for long-term outcome in adjuvant trials. Genome-wide monitoring of gene expression using DNA microarrays makes it possible to study thousands of genes in a tumor sample with a single experiment. By looking for an association between the gene expression pattern and tumor behavior, it should be possible to identify new prognostic and predictive factors. Dr M Van de Vijver (Rotterdam, The Netherlands) and his team have previously identified a 70gene expression profile (GEP) associated with an increased risk for developing distant metastases within 5 years. More recently, they identified consistent features in the transcriptional response of normal fibroblasts to serum and used this wound-response signature to reveal links between wound healing and cancer progression in the same tumors. By combining the 70-GEP (good-prognosis and poor-prognosis tumors) and the wound signature (activated and quiescent tumors), subgroups of patients with markedly different prognoses can be identified [1]. One serious limitation of microarray expression profiling, however, is that it is an RNA assay that requires fresh or well-preserved frozen tissue for extraction of viable RNA. Consequently, some investigators use microarrays to screen the genes for those factors associated with outcome and then develop classifiers for clinical applications that are based on subsequent studies using reverse transcriptionpolymerase chain reaction (RT-PCR) of the selected genes. This was the approach used and reviewed in detail by Dr S Paik (PA, USA) in developing the Oncotype Dx® risk score for patients with lymph node-negative, estrogen