S-phase fraction combined with other patient and tumor characteristics forthe prognosis of node-negative, estrogen-receptor-positive breast cancer

Women with estrogen-receptor (ER)-positive breast cancer and no axillary ly mph-node involvement are considered to have excellent overall prognosis. Ho wever, this population is not homogeneous with regard to risk of recurrence ; in fact, some of these patients have a prognosis no better than that of m any women with ER-negative tumors or positive axillary nodes. Consequently, better tumor markers and better use of those currently available are neede d to distinguish patients who would benefit from more aggressive therapy fr om those for whom such therapy is unnecessary. A well-defined cohort of over 4000 breast cancer patients from National Sur gical Adjuvant Breast and Bowel Project (NSABP) Protocol B-14 who had ER-po sitive tumors and no axillary lymph-node involvement was analyzed to ascert ain the usefulness of tumor cell S-phase fraction for prognosis. The signif icance of clinical tumor size, patient age at surgery, ER and progesterone receptor (PgR) expression, and nuclear grade was also explored. Statistical methods based on smoothing splines were used to relate treatment failure a nd mortality rates to patient and tumor characteristics. Models for 5- and 10-year disease-free survival (DFS) and overall survival were developed and summarized. The attenuation of the prognostic importance of covariates ove r time was investigated. After other characteristics were accounted for, a strong association was fo und between S-phase fraction and DFS, as well as survival. Tumor size, pati ent age at surgery, and PgR status were also significantly associated with outcome. The diversity of risk in the B-14 population was more extreme than is generally recognized. The prognostic capabilities of S-phase, tumor siz e, and PgR status were sharply attenuated as the time from surgery increase d.