Abstract 1760: Mitotic activity index and bone marrow micrometastsis detection is a strong prognostic combination in lymph node positive and negative breast cancer
Authors: Gilje Bjørnar , Nordgård Oddmund , Janssen Emiel , Tjensvoll Kjersti , Småland Rune , Baak Jan P.A. 
Published: February 2011

Abstract
PURPOSE: To investigate the prognostic value of Mitotic Activity Index (MAI) in lymph node negative and lymph node positive operable breast cancer patients in an unselected population and to compare it to bone marrow (BM) micrometastatis status.
PATIENTS AND METHODS: Analysis of MAI assessed using a strict protocol with proven strong prognostic value (Baak JP et al. in: JCO 2005, Ann Oncol 2008 and Breast Cancer Res Treat 2009) was compared to classic prognosticators and BM micrometastases detected by a real-time RT-PCR multimarker assay including mammaglobin, cytokeratin 19 and TWIST1 mRNA in 179 consecutive early breast cancer patients (median follow-up: 96 months; range: 0 to 126 months). RESULTS: Systemic relapse occurred in 31 patients (17.3%) and 26 (14.5%) of these patients died of breast cancer-related causes. MAI (&lt;10, &gt;=10) was strongly associated with recurrence both in lymph-node (LN)-negative (HR 3.4, Confidence Interval (CI) 1.11-10.66) but less so in LN-positive patients (HR: 2.2, CI 0.87-5.62). BM-status was highly significant in LN-positive patients (HR: 3.7, CI 1.5-9.22) but not in LN-negative patients (HR: 2.4, CI 0.65-8.81). With multivariate Cox regression, BM micrometasis status and MAI were the strongest variables in LN-positive patients for both recurrence-free survival (HR 3.7, CI 1.5 −9.2 and HR 2.2, CI 0.9-5.7 respectively) and breast cancer specific survival (HR 3.3, CI 1.25-8.49 and HR 3.1, CI 1.1-8.9, respectively). In the LN-negative population ER was the strongest prognosticator (HR 0.24, CI 0.08-0.8) for systemic relapse, whereas MAI was the only significant variable in breast cancer specific survival (HR 7.0, CI 1.7-27.9). A multimarker panel including both BM-status and MAI was explored and was found to be the most significant prognostic marker in both LN-positive (HR 4.4, CI 1.3-15.3 / HR 6.0, CI 1.4 to 26.4) and LN-negative (HR 4.1, CI 1.0-16.5 / HR 7.7, CI 1.2-50) for both systemic recurrence free survival and breast cancer specific survival, respectively, in multivariate Cox regression. CONCLUSION: MAI and BM micrometastatic status are independent prognostic factors and supplementary to each other in identifying patient groups with poor prognosis. Patients with high mitotic activity tend to relapse early, whereas BM micrometastatic disease predicts a constant risk over time. The combination of the proliferation marker MAI and assessment of BM micrometastasis is the strongest prognostic marker in both the LN-positive and LN-negative subgroups of 179 early breast cancer patients. This allows better identification of patients at need for more aggressive treatment and warrants validation in a larger trial.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1760.