Annals of oncology : official journal of the European Society for Medical Oncology
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Currently, much effort is being invested in the identification of new, accurate prognostic and predictive factors in breast cancer. Prognostic factors assess the patient's risk of relapse based on indicators such as intrinsic tumor biology and disease stage at diagnosis, and are traditionally used to identify patients who can be spared unnecessary adjuvant therapy based only on the risk of relapse. Lymph node status and tumor size are accepted as well-defined prognostic factors in breast cancer. ⋯ Despite recent advances in the understanding of breast cancer biology and changing practices in disease management, with the exception of hormone receptor status, which predicts responsiveness to endocrine treatment, no predictive factor for response to systemic therapy in breast cancer is widely accepted. While gene expression studies have provided important new information with regard to tumor biology and prognostication, attempts to identify predictive factors have not been successful so far. This article will focus on recent advances in prognostication and prediction, with emphasis on findings from gene expression profiling studies.
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Expanding knowledge, together with implementation of new techniques, has fuelled the area of translational medical research aiming at improving prognostication as well as prediction in cancer therapy. At the same time, new discoveries have revealed a biological complexity we were unaware of only a decade ago. Thus, we are faced with novel challenges with respect to how we may explore issues such as prognostication and predict drug resistance in vivo. ⋯ This paper discusses clinical settings for studying drug resistance in vivo together with a discussion of contemporary biology in this field. Notably, each individual parameter which has been found correlated to drug resistance in vivo so far represents either a direct drug target or a factor involved in DNA repair or apoptosis. On the basis of these findings, we suggest drug resistance may be explored on the basis of upfront biological hypotheses.
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Aberrant activation of some members of human epidermal growth factor receptor (HER) family plays a key role in breast carcinogenesis. Lapatinib is an oral dual tyrosine kinase inhibitor selective for inhibition of epidermal growth factor receptor (EGFR/ErbB1) and HER2/ErbB2. Having more targets, probably its antitumor activity could be more efficient. ⋯ Interim results from the large, phase III trial in 392 patients showed that in combination with capecitabine lapatinib almost doubled time to progression when compared with capecitabine alone. Several clinical trials that explore the efficacy of lapatinib in combination with conventional chemotherapeutic agents [paclitaxel (Taxol), capecitabine and platinoids], hormonotherapy and other target therapies are ongoing in advanced breast cancer or in neo-adjuvant and adjuvant settings. Our improved understanding of the biology of breast cancer and the use of biomarkers for identification of specific subtypes are allowing us to bring patient-specific novel therapies such as lapatinib to the clinic.