Prediction of prognosis in human breast cancer : a study on clinicopathologic and cytometric prognostic factors

Sammanfattning: This study was undertaken to evaluate some important prognostic factors in human breast cancer. The prognostic value of accepted clinicopathological factors such as the presence of axillary lymph node métastasés, histologic grade, clinical and pathological stage was confirmed.In a cohort of stage T3,T4,M0 breast cancer with 91 patients (paper I) DNA ploidy by static cytometry (SCM) turned out to be the most important prognostic factor. In a cohort of stage T2,M0 breast cancer with 99 patients (paper III) the presence of involved axillary nodes and low histologic grade were independent prognostic factors. According to life-table analyses DNA ploidy by flow cytometty (FCM) and SCM were significant prognostic predictors for survival but S-phase fraction (SPF) was not. The significant discrimination between euploid and aneuploid tumours was seen also among the node-negative patients. In a patient material with 158 tumours of predominantly low stages (73% T0,T1, papers IV and V) and calculated mammographie tumour volume doubling time (DT) DNA ploidy by FCM gave no significant prognostic information. A computer program was used to calculate SPF from the histograms obtained by FCM. SPF with a cut-off value of 7.5% between tumours with high and low proliferation rate was a highly significant and independent prognostic factor for survival. The other independent prognostic predictors were low histologic grade, the presence of involved axillary nodes and stage II and III (versus stage I).DT values for 158 patients (papers IV and V) varied between 0.6 and 65.8 months (mean 10.9 months) and 11 tumours showed no growth at all between mammographies. The median value of 9.0 months was chosen as cut-off point between slow and fast growing tumours. The prognostic power of DT was however low, and the difference between slow and fast growing tumours was significant only for distant disease-free survival. Seventy-one of the 158 tumours were detected by mammographie screening. The screening detected carcinomas with predominantly long DT:s were discovered at an early stage and showed favourable characteristics concerning DNA ploidy and SPF.FCM was a rapid and reliable method for DNA analysis with a better prognostic discrimination between euploid and aneuploid groups than SCM (papers II and III).SPF, DNA ploidy and histologic grade are significantly correlated to one another but show no strong correlation to the presence of axillary lymph node métastasés. There is also a significant correlation between DT on one hand and DNA ploidy and SPF on the other hand.In conclusion the classic prognostic factors are still valuable. DNA ploidy as a single prognostic factor seems to have a relatively low prognostic power and seems to be of limited clinical value. SPF is a highly significant prognostic predictor for breast cancer of low stage, but the clinical value is not defined.