Early Changes in Apoptosis and Proliferation to Predict Response and Resistance to Chemotherapy in the Treatment of Breast Cancer
Abstract
The project has 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, and (2) to develop an automated method for analysing apoptosis in fine needle aspirates (FNAs) taken from breast carcinomas. Aim (1): we have confirmed that apoptosis significantly increases 24 hours after starting chemotherapy and demonstrated that proliferation also falls by a mean of approximately 30% at this time. Change in apoptosis after 24h was not closely related to clinical response in a trial in which patients also received tamoxifen. A trial in which tamoxifen is excluded has been initiated. Patients who are c-erbB2 positive have a reduced likelihood of showing an increase in apoptosis after 24 hours. Aim (2) flow cytometry is unlikely reliably to separate the apoptotic population of cells from normal cells but our preliminary work with Laser Scanning Cytometry indicates that this approach should be applicable to FNAs. Apoptotic MCF7 cells after camptothecin treatment can be quantified by LSC in a manner which allows morphologic confirmation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA378097
Entities
People
- Mitchell Dowsett