Early Changes in Apoptosis and Proliferation to Predict Response and Resistance to Chemotherapy in the Treatment of Breast Cancer

摘要

The project had 2 interconnecting aims: (1) to confirm and extend the observations, that apoptosis is increased and proliferation is decreased in primary breast cancer shortly after chemo and endocrine therapy, such that the predictive power of these changes for clinical response can be assessed, (2) to develop an automated method for analyzing apoptosis in fine needle aspirates (FNAs) taken from breast carcinomas. In the final period of this grant we have found that induction of apoptosis does not occur in response to all hormonal agents for breast cancer treatment: in contrast to tamoxifen, aromatase inhibitors reduce the apoptotic index in the first 2 weeks of treatment. In chemotherapy treated patients a significant relationship between apoptosis and response to treatment was found in a pilot study. The deficits of flow cytometry led us to evaluate laser scanning cytometry (LSC) for measuring a variety of biomarkers in fine needle aspirates, including apoptosis. A good relationship was found between levels of Ki67 as measured by LSC and measurements made by visual microscopy. Application of this method to clinical samples for apoptosis measurement will require the elimination of artifacts. Changes in proliferation are a useful intermediate end-point for response. Apoptotic changes may be similarly useful for chemotherapy but technical challenges remain to simplify its analysis.