Analysis of PI3K/mTOR Pathway Biomarkers and Their Prognostic Value in Women with Hormone Receptor–Positive, HER2-Negative Early Breast Cancer

摘要: BACKGROUND: The PI3K/AKT/mTOR pathway alterations have been shown to play significant roles in the development, progression, and metastatic spread of breast cancer. Furthermore, they implicated process drug resistance, especially endocrinal therapies. In this study, we aimed define correlation between PI3K mutations expression phosphorylated forms different downstream molecules women with estrogen receptor (ER)–positive, human epidermal growth factor 2–negative (luminal) early cancer treated at Cairo university hospitals. METHODS: Next-generation sequencing was used detect PIK3CA hotspots (in exons 9 20). Immunohistochemistry performed on tissue microarray blocks prepared from samples 35 Egyptian luminal patients pathology department Centre Leon Berard (CLB). intensity percentage stained tumor cells were integrated high versus low biomarker expression. cytoplasmic nuclear stainings graded separately. Patients followed for a median 4.7 years (2.1 6.9 years). Correlation done immunohistochemistry pAKT, LKB1, p4EBP1, pS6 ribosomal protein (pS6RP) clinicopathologic features disease free survival (DFS) patients. RESULTS: Median age diagnosis 51.3 (range, 25 82 Tumors larger than 20 mm 79.2% cases, whereas 57.9% had axillary lymph node deposits. Only 12.3% SBR grade I tumors, 50.8% II, 36.8% III. ERs negative 6 (17%) after review. Thirty-two cases assessable LKB1 33 p4EBP1 pS6RP, 24 mutations. Nuclear pS6RP 65.6%, 62.5%, 68.8%, 42.4%, 57.6%, respectively. found 7 (29.2%). correlated localization pAKT (i.e., decreased P = .04; increased .10). There tendency toward an inverse (P .10) .19). marker good prognosis. It associated smaller tumors .05), more ER .08) progesteron (PgR) positivity .002). Kaplan Meier (KM) model, longer DFS (hazard ratio 0.36; 95% confidence interval, 0.15-1.10; .08). also carried 0.51; 0.11-1.16; .13). mutational status did not show any prognostic significance our cohort. CONCLUSION: Among studied biomarkers, only tended predict better mutation but or p4EBP1.