P2-12-22: A Prognostic Index Composed of Progesterone Receptor Status, Tumour Size and S-phase Fraction, Predicts Survival in Node-Negative Breast Cancer Patients in a Large Multicentre Prospective Cohort Study.

Abstract

Abstract Background The importance of the added prognostic value of proliferation, either single factors such as Ki67 or flow cytometric S-phase fraction (SPF), or as the main common denominator in the majority of gene expression profiles, has been highlighted over the last years in node-negative breast cancer. There are however few published prospective studies. In an earlier retrospective study on node-negative breast cancer from our group, a prognostic index consisting of PR status, tumour size and a proliferation factor, SPF, identified one third of the patients as high risk, with a fourfold increased risk of distant recurrence. The present study was set up to validate this index in a large prospective multicenter cohort study with long term follow-up. Material and Methods: 596 patients from 3 regions in Sweden were between 1991–1995 included in the study. Inclusion criteria were: 10mm≤tumour size≤50mm, node-negativity, ≥5 lymph nodes removed, age <60 years, and radical surgery. Patients with bilateral breast cancer or previous malignancy were excluded. Prospective analyses of ER, PR, and flow cytometric SPF were performed. High- risk was defined as 2 or more of the following: 1. size >20mm 2. PR- (in the absence of PR status, ER-) and 3. high SPF (in the absence of SPF, Bloom Richardson grade 3). 82% of the patients received no adjuvant medical treatment. Cox proportional hazards regression, stratified for centre, was used to model the impact of the index on breast cancer specific survival (BCSS). Median follow-up was 16 years for the 452 patients alive at last follow-up. Analyses were done after 5 and 10 years follow-up, during which 42 and 95 patients, respectively, died of breast cancer. Results: 31% of the patients were identified as high-risk. In univariate analysis, the index was prognostic for BCSS after 5 years (HR 5.1, 95%CI: 2.7−9.8,) as well as 10 years (HR 2.2, 95%CI: 1.5−3.4). The prognostic impact remained significant after adjustment for adjuvant medical treatment and age. The 5- and 10-year BCSS (95%CI) was 97% (94-98) and 87% (83-90) for low risk patients, compared with 85% (79-89) and 76% (69-81) for high risk patients. In the group with no risk factors (n=218 ), no patient died of breast cancer during the first 5 years. Proliferation was the strongest factor for BCSS followed by PR and tumour size, both in uni- and multivariate analyses. In multivariate analysis, adjusted for adjuvant treatment and age, the HR for proliferation was 7.5 (95%CI: 3.2-18) after 5 years and 2.5 (95%CI: 1.6−4.0) after 10 years. Discussion: This large prospective multicenter cohort study validates the results from an earlier retrospective study, that a prognostic index consisting of PR status, tumour size and a proliferation factor, SPF, reliably identifies one third of the node-negative patients with a high risk of relapse. The index also identifies an extreme low risk group; patients with no risk factors, with 100% 5-year survival. This group could be spared adjuvant medical treatment, especially chemotherapy. Taken together, this index may be clinically helpful for prognostic considerations and for selection of adjuvant treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-22.