Asunto(s)
Antineoplásicos/farmacología , Proteínas Portadoras/fisiología , Resistencia a Medicamentos/genética , Glicoproteínas de Membrana/fisiología , Proteínas de Neoplasias/fisiología , Neoplasias/tratamiento farmacológico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Animales , Antineoplásicos/farmacocinética , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/genética , Estudios de Factibilidad , Regulación Neoplásica de la Expresión Génica , Humanos , Glicoproteínas de Membrana/antagonistas & inhibidores , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/genética , Ratones , Ratones Transgénicos , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/genética , Neoplasias Experimentales/metabolismo , Trifluoperazina/farmacología , Trifluoperazina/uso terapéutico , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismo , Verapamilo/farmacología , Verapamilo/uso terapéuticoRESUMEN
With improved screening and education, a greater proportion of breast cancer is detected at an early stage. Although the prognosis for many of these patients is excellent following definitive local therapy alone, some subsets of node-negative patients have a 30% chance of eventually developing metastatic disease that will be incurable with current therapy. Thus, an increasing proportion of early-stage patients are being offered some form of adjuvant therapy, with the expectation of improved relapse-free survival, and possibly improved overall survival. Efforts have been made to base the selection of patients for adjuvant therapy on specific prognostic factors. Meanwhile, the scope and complexity of putative prognostic factors continues to widen, and now includes such items as the presence of occult microscopic metastases, DNA ploidy and proliferative fraction, cytogenetic abnormalities, oncogene expression, growth factor receptors, and expression of hormonally regulated proteins. In addition, there is now a considerable range of options with regard to the composition, dose intensity, and sequence of multimodality therapy. Data regarding the classification, significance, and interpretation of prognostic factors is reviewed together with the development, current status, and recommendations regarding adjuvant therapy for patients with early-stage breast cancer. For 1991, the National Cancer Institute (NCI) has estimated that 175,000 new cases of breast cancer will be diagnosed in American women. It is also estimated that 44,500 women will die of breast cancer. Unfortunately, the age-adjusted death rate from breast cancer has shown no overall change from 1930 through 1987. However, effective screening techniques continue to identify an increasing percentage of early-stage tumors, which should exceed 50% of all new tumors in 1991. Ultimately, our understanding of environmental and genetic risk factors may identify new ways to reduce the impact of this disease. In the interim, development and application of effective systemic adjuvant chemotherapy and hormonal therapy has become increasingly important. There is no question that a greater proportion of patients with less extensive disease are now being offered some form of adjuvant therapy. Meanwhile, selection of patients for adjuvant therapy, and choice among specific adjuvant regimens, has remained controversial. Analysis of multiple prognostic factors is performed not only in the context of cooperative investigational trials, but more often in the offices of individual physicians caring for individual patients. Tumor biopsies can now be routinely sent to specialized laboratories for performance of complex assays with potential prognostic information, although interpretation of these results with reference to a specific patient is often uncertain.(ABSTRACT TRUNCATED AT 400 WORDS)