Activation of the mTOR signaling pathway in breast cancer and its correlation with the clinicopathologic variables

• DOI: 10.1007/s10549-007-9746-x
• Publication Date: 2007-09-05T18:31:34Z
• Authors: Woo Chul Noh; Yang Hee Kim; Min Suk Kim; Jae Soo Koh; Hyun-Ah Kim; Nan Mo Moon; Nam-Sun Paik
• Keywords: Adult; Sirolimus; Antibiotics, Antineoplastic; Ribosomal Protein S6 Kinases; TOR Serine-Threonine Kinases; PTEN Phosphohydrolase; Breast Neoplasms; Middle Aged; Prognosis; Immunohistochemistry; Disease-Free Survival; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Drug Resistance, Neoplasm; Tissue Array Analysis; Biomarkers, Tumor; Humans; Female; Protein Kinases; Proto-Oncogene Proteins c-akt; Aged; Signal Transduction

Rapamycin and its analogues are currently being tested in clinical trials as novel-targeted anticancer agents. Pre-clinical studies that used breast cancer cell lines have suggested that p-Akt or p-S6K1 expressing tumors, as well as PTEN negative tumors, were sensitive to rapamycin. The aims of this study were to determine the proportion of breast cancer that could be candidates for rapamycin treatment and to elucidate the clinicopathologic characteristics and prognosis of potentially rapamycin-sensitive tumors.We evaluated the expressions of PTEN, p-Akt and p-S6K1 by performing immunohistochemistry in 122 breast cancer tissues. We analyzed the association of the expression of these proteins with the cliniopathologic variables and the disease-free survival.PTEN negative tumors, p-Akt expressing tumors and p-S6K1 expressing tumors constituted 4.1% (5/122), 41.0% (50/122), and 36.1% (44/122) of the total tumors, respectively. The proportion of tumors that met the criteria of rapamycin sensitivity was 54.9% (67/122). We could not find any significant correlation between the expression of these proteins and the other prognostic factors. However, the prognosis of tumors with a p-S6K1 expression was significantly worse than that of the p-S6K1 negative tumors.Based on the status of the PTEN, p-Akt and p-S6K1 expressions as predictors of rapamycin sensitivity, this study suggested that over 50% of breast cancer patients could be potential candidates for rapamycin treatment. In addition, the p-S6K1 expression may constitute an independent prognostic factor for disease-free survival.