Prognostic Significance of PIK3CA Mutations and Immunophenotypes in Lymph Node-Positive Breast Carcinomas.
Francisco I Aranda, Laura Sanchez-Tejada, Cristina Alenda, Gloria Peiro, Javier Segui, Maria Niveiro, Artemio Paya, Juan B Laforga, Enrique de Alava, Jose Palacios, Miguel Martin. Hospital General Universitario, Alicante, Spain; Centro Investigación del Cáncer, Salamanca, Spain; Hospital Virgen del Rocío, Sevilla, Spain; GEICAM, Madrid, Spain
Background: PIK3CA activating mutations have been identified in approximately one-fourth of breast carcinomas (BC), which in turn activate the PI3K/Akt pathway and contribute to tumor progression. The purpose of the study was to evaluate PIK3CA mutations in a series of lymph node-positive (LNP) infiltrating BC stratified by immunophenotypes and its prognostic significance.
Design: A total of 501 LNPBC patients included in the GEICAM 9906 clinical trial were studied. Immunohistochemistry (IHC) was applied on tissue microarrays for ER and PgR (cut-off Allred score 3), Ki67 (cut-off 15%), p53 (cut-off 20%) and HER2 (all 2+ and <30% 3+ confirmed by dual-CISH).Tumors were classified according to immunophenotype as luminal A (ER and/or PgR positive, HER2-negative, Ki67 low and p53 negative), luminal B (ER and/or PgR positive, HER2-negative, Ki67 high and/or p53 positive), HER2-positive and triple-negative (ER/PgR/HER2-negative), DNA was extracted from formalin-fixed paraffin-embedded tissues using standard methods. PIK3CA mutation analysis was performed by allelic discrimination based on real-time chemistry TaqMan MGB probes in ABI Prism 7500 Sequence Detection System (Applied Biosystems) in 397 BC. Minimun clinical follow-up 98 months. Disease-free and overal survival (DFS and OS) were calculated by the Kaplan-Meier method (log rank test). A p-value <0.05 was considered significant.
Results: PIK3CA mutations were observed in 24% tumors, ER positive in 83%, PgR in 67%, high Ki67 in 31% and p53 positive in 35%. Immunophenotypes were as follows: 42% luminal A. 30% luminal B, 9% HR+/HER2+, 5% RH-/HER2+, and 13% HR-/HER2-. DFS and OS was better for patients with HER2-negative, ER+, PR+, p53-negative tumors, and specifically for those with luminal A and B subtypes (log rank p<0.05). However, PI3KCA mutations and Ki67 showed only a trend (p=0.19 and p=0.15, respectively).
Conclusions: Our data in a series of LNPBC support that tumor stratification according to immunophenotypes has prognostic relevance. However, PI3KCA mutation status does not proportion additional information.
Supported by grant FIS 06/1488
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 4, Wednesday Afternoon