A prospective, multicenter validation study of a prognostic index composed of S-phase fraction, progesterone receptor status, and tumour size predicts survival in node-negative breast cancer patients: NNBC, the node-negative breast cancer trial

In a retrospective study on node-negative breast cancer, a prognostic index consisting of a proliferation factor, S-phase fraction (SPF), progesterone receptor status (PR), and tumour size identified one-third of patients as high risk, with a sixfold increased risk of breast cancer death. This prospective multicenter cohort study was set up to validate the index. In 576 T1-2N0 patients < 60 years, prospective analyses of PR and SPF were carried out. High risk was defined as >= 2 of the following: size > 20 mm, PR-negativity, and high SPF (in the absence of SPF, Bloom-Richardson grade 3). Median follow-up was 17.8 years. Thirty-one percent were high risk. In univariate analysis, the index was prognostic for breast cancer-specific survival after 5 years [hazard ratio (HR) = 4.7, 95% confidence interval (95% CI) 2.5-8.9], 10 years (HR = 2.2, 95% CI 1.5-3.3), and 15 years (HR = 1.7, 95% CI 1.2-2.5), and remained significant after adjustment for adjuvant medical treatment and age. In the 37% of patients with no risk factors, only one patient died of breast cancer the first 5 years. This prospective study validates a prognostic index consisting of a proliferation factor, PR-status, and tumour size. The index may be helpful for prognostic considerations and for selection of patients in need of adjuvant therapy.