Combined analysis of vascular invasion, grade, HER2 and Ki67 expression identifies early breast cancer patients with questionable benefit of systemic adjuvant therapy

Introduction. Over-treatment of low-risk early breast cancer patients with adjuvant systemic therapies is an important clinical challenge. Better techniques are required which can be used to distinguish between the large group of patients with no residual disease after surgery and consequently no benefit of adjuvant treatment, from the smaller group with high relapse risk. A better integration of available prognostic factors might contribute to improved prediction of clinical outcome. Material and methods. The current study included 346 unselected pT1pN0 patients who did not receive adjuvant systemic treatment. In Norway, no patients with this stage were recommended systemic treatment at the time of the study (1995 1998). Histological type, tumour size, grade, vascular invasion (VI), hormone receptor (HR) status, HER2 and Ki67 (cutoff 10%) were analysed. Median follow-up was 86 months for relapse and 101 months for death. Results. Thirty-eight patients experienced relapse, 31 with distant metastasis. Twenty-one patients died of breast cancer. In univariate analysis grade, HER2, HR, VI and Ki67 had impact on clinical outcome (p < 0.005, log rank). In multivariate analysis, only grade 1 2 vs. grade 3, HER2, VI, and Ki67 status were significant for disease free survival, distant disease free survival, and/or breast cancer specific survival. These factors were used in combination, to separate patients into groups based on the number of unfavourable factors present [combined prognostic score (CPS) 0-4]. Close to 2/3 of the patients (61.4%) had no unfavourable factor (CPS0), whilst 18.4% had CPS >= 2. Only 3.6% of those with CPS0 developed metastasis (p < 0.001). The outcome was clearly worse for patients with CPS >= 2 (p < 0.001), systemic relapse was detected in approximately 40%. Conclusions. This study indicates that the combined use of grade, VI, HER2 and Ki67 identifies a subgroup of breast cancer patients with a relapse risk that may question the benefit of adjuvant systemic therapy.