Prediction of Metastasis in Node-Negative, Hormone Receptor Positive, Tamoxifen Adjuvant Treated Primary Breast Cancer Patients Using Ki-67 (IHC) and RT-PCR Based 14-Gene Prognostic Signature.

Abstract

Background: Risk estimation based on the recommendations of St. Gallen Consensus commonly decides for additional cytostatic therapy in node-negative (N-), hormone receptor positive (HR+) primary breast cancer patients. High proliferative activity in the HR+ subtype confers a 19-fold relative risk of relapse compared with HR+ tumors of low proliferative activity. Furthermore immunohistochemically determined Ki-67 is characterized as a Luminal B marker that identifies a high risk subgroup in HR+, N- breast cancer patients.Aim of this investigation was to compare risk estimation using Ki-67 (%) with the results of a RT-PCR based multi-gene prognostic signature. Methods: Tumor tissues of totally 321 unselected primary breast cancer patients were formalin fixed and routinely processed for immunohistochemical determination and scored for protein expression of ER, PgR and Ki-67. HER2 was determined using dd-PCR. Content of both hormone receptors and proliferation activity were evaluated counting positively coloured nuclei from at least 100 tumor cells. The median follow up was 61 months. To calculate the cut off for high proliferation Ki-67 values were subjected to a log rank CART analysis. High proliferation was defined by Ki-67 of 19% and more. With this cut off it was possible to distinguish significantly various patient cohorts (N-, pT1, postmenopausal) into two different risk groups regarding metastasis free survival. The definition of low risk was low proliferation and HER2 negativity, of high risk high proliferation or HER2 positivity. The risk for metastasis of 16 new primary breast cancer patients was estimated based on two surrogate risk groups and the multi-gene prognostic signature. Results: Tamoxifen adjuvant treated HR+, HER2-, low proliferating (Ki-67 <19%), N- low risk patients (N= 68) and HR+, HER2-, high proliferating/HR+, HER2+, N- high risk patients (N= 84) showed a recurrence rate of 2.94% and 27.4%, respectively (P< .000). In the ongoing observation study all 5 low proliferating HER2- tumors had a low risk gene prognostic signature. From 11 high proliferating HER2- patients one patient had a low risk gene signature (9%), 3 patients a moderate risk gene signature (27%) and 7 patients a high risk gene signature (64%). Conclusion: Despite the small number of patients investigated up to now (N= 16) the preliminary results appear to show that low proliferative activity is associated with a low risk gene prognostic signature, whereas high proliferation means only in part a high risk gene prognostic signature. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6025.