S-phase fraction and breast cancer--a decade of experience

During the past decade, more than 300 articles, abstracts, and book chapters have been published about S-phase fraction (SPF) determined by DNA flow cytometry and its clinical utility for patients with breast cancer. However, the use of SPF for making treatment decisions for breast cancer patients remains controversial. After reviewing 273 published articles, we conclude: 1) Despite different techniques and cutpoints, correlations between SPF and other prognostic markers are relatively consistent across studies; higher SPF is generally associated with worse tumor grade, absence of steroid receptors, larger tumors, and positive axillary lymph nodes. 2) Higher SPF is generally associated with worse disease-free and overall survival in both univariate and multivariate analyses; SPF values from laboratories that have conducted validation studies can be used, in combination with other factors, to estimate the prognosis of patients with primary breast cancer. 3) There is considerable variability among laboratories regarding assay methodology, cell-cycle analysis techniques, and cutpoints for classifying and interpreting SPF; use of SPF values from different laboratories is problematic, and there remains a need for standardization of these processes and well-designed confirmation studies. We conclude that measurement of SPF does have clinical utility for patients with breast cancer, but standardization and quality control must be improved before it can be routinely used in community settings.