Use Of Immunohistochemical Profiling A Of Node-Negative Breast Carcinomas For Prediction Of Metastatic Risk

10636 Background: Early-stage breast carcinomas particularly those with lymph node negative disease have recently increased due to screening programs. Patients with node negative breast cancer have a fairly good 10 year overall survival with locoregional treatment alone. However most of the patients are offered chemotherapy causing an important proportion of over treatment. Therefore markers identifying patients not requiring aggressive adjuvant therapy are urgently needed in order to avoid to unnecessarily expose women to potential toxicity and side effects of this treatment. In this study, we searched for a prognostic immunohistochemical signature indicative of risk of early metastasis in node-negative breast carcinomas that would be also relevant for the development of new tailored therapy. Methods: Quantitative measurements immunohistochemical expression of 64 markers (selected from literature data) using high-throughput densitometry (as continuous variables), of digitised microscopic micro-array images were correlated with clinical outcome in 667 node-negative breast carcinomas (mean follow-up 102 months). Multivariable (fractional polynomials) model of logistic regression allowed the selection of the best combination of markers (in terms of sensitivity and specificity) to predict patients' outcome without any categorisation using predefined cut-points for individual marker measurements. Results: A highly predictive ten-marker (out of 64) signature was identified comprising PI3K, pmTOR, pmapKAPk-2, SHARP-2, P21, HIF-1α, Moesin, p4EBP-1, pAKT and P27 that well classified 91.4 % of node-negative patients (specificity 90.9 %, sensitivity 93.7%, area under ROC curve 0.958) independently of estrogen receptors (ER), and progesterone receptors (PR) and HER-2 status (91.6 % well classified patients when ER, PR, HER-2 excluded). Conclusions: It is concluded that quantitative immunoprofiling of node-negative breast carcinomas is helpful in selecting patients who should not receive aggressive adjuvant chemotherapy and provides data for the development of tailored therapy. No significant financial relationships to disclose.