Combining Genomic Profiling (70 Gene-Mammaprint) with Nodal Status Allows To Classify Patients with Primary Breast Cancer and Positive Lymph Nodes (1-9) into Very Distinct Prognostic Subgroups That Could Help Tailor Treatment Strategies.

Abstract

Abstract OBJECTIVESThe axillary lymph node (LN) status is considered to be one of the most important factors for chemotherapy decision-making of operable breast cancer patients (pts). It is commonly agreed that combination therapies with taxane-containing regimens should be recommended for these pts, whereas high-dose regimens have failed to provide further improvement for pts clinically considered at high-risk.It has previously been shown that the 70-gene profile (MammaPrint®TM), which was developed in node-negative patients is excellent in predicting disease outcome in pts with 1-3 positive nodes and similarly in pts with 4-9 positive-nodes. Further analysis based on adjuvant treatment received and pooled analysis of the 2 LN positive series was performed in order to assess the prognostic added-value of genomic profiling in LN positive pts.METHODS Frozen tumor samples from breast cancer pts with positive LN coming from 2 hospitals were selected in consecutive series (1-3 LN, 4-9 LN; all female, diagnosed between 1984 and 1995, primary invasive breast carcinoma, unilateral T1, T2 or operable T3, mastectomy or breast-conserving therapy, no prior malignancies, fresh frozen tumor material available). Samples were evaluated by gene expression profiling for the 70-gene profile and were classified as genomic high risk (poor prognosis) or genomic low risk (good prognosis).RESULTS A total of 519 pts have been analyzed: 346 with 1-3 positive LN (PN1) and 173 with 4-9 positive LN (PN2). Among them, 212 (41%) had the 70-gene good prognosis-profile and 307 (59%) had the 70-gene poor prognosis-profile (strictly equal proportions among the 2 LN groups). Median follow-up was 10.3 years: distant metastases occurred in 141 patients (116 as first event) and 103 (20 %) died of their disease. Distance metastases as first event and breast cancer specific survival according to LN group (PN) and genomic profile (MP) are shown in Figures 1 and 2.CONCLUSION Our data show that the 70-gene profile is a strong prognostic marker of distant recurrence and breast specific death in breast cancer patients with positive LN. Combining nodal status (1-3 nodes vs. 4-9 nodes) and 70-gene profile (good vs. poor) allows stratifying patients among subgroups for whom tailored treatment strategies should be designed and assessed based on their very different outcome. Pts with elevated number of lymph nodes and high genomic risk have a very poor prognosis and might need to be considered for stronger treatment strategies. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 102.