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Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors.

"Giant" 2-D gel electrophoretic protein separations (Methods Enzymol 91, part I, 190-214, 1983) offer a significant increase in resolving power over the usual methods. The increased capacity (good resolution up to 1 mg and as much as 10 mg of sample can be applied) and the improvement in resolution reveal some 3000 individual proteins when whole-cell extracts from diverse sources are separated on broad-range (pH 4.5-7.5) isoelectric-focusing (IEF) gels, and an additional 2000 when non-equilibrium and lower pH range IEF gels are also run. When applied to several types of steroid target cells, the giant-gel methods have allowed detection, among the minor protein species not resolved on standard-size gels, of a group of rapidly evolving (within the first 30 min or so) adrenal glucocorticoid inductions. These are likely mediators of the characteristic hormone effects. The giant gels have also greatly expanded the range of changes in protein gene-products in response to heat shock, growth factors, and retrovirus-induced malignant transformation, and should substantially enlarge the number of protein polymorphisms useful in genetic studies for linkage mapping.

The instrumentation requirements for agricultural research in the 21st century hinge on whether or not complete analyses of animal and plant cells will be required, on the cost of performing the analyses, and on the cost and complexity of the analytical instrumentation needed. It is emphasized that nature’s response to modern agriculture is to evolve pests and diseases better fitted to attack new genetically uniform plants, or to escape pesticides or herbicides. For all future history, new strains of crop plants, new herbicides and pesticides, and new animal strains will be required periodically. Existing native plant varieties now provide genes for resistance which are empirically discovered, and bred into high-yield strains by conventional methods. It is suggested that this process will not be endlessly successful, and that at some future time the required genes will not be found. Then, true genetic engineering with rational design and optimization will be required. This means the complete sequencing of plant and animal genomes, the identification and characterization of all gene products, computer modelling of cell function, and ultimately the introduction of sets of modified or totally synthetic genes. We review the status of some of the instruments required, and suggest future directions for their development.