Xuedong Yin1, Roger H Kim2, Guang Sun2, Janet K Miller2, Benjamin D Li3. 1. Department of Surgery, Louisiana State University Health Sciences Center, Feist-Weiller Cancer Center, Shreveport, LA; Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. 2. Department of Surgery, Louisiana State University Health Sciences Center, Feist-Weiller Cancer Center, Shreveport, LA. 3. Department of Surgery, Louisiana State University Health Sciences Center, Feist-Weiller Cancer Center, Shreveport, LA. Electronic address: bli@lsuhsc.edu.
Abstract
BACKGROUND: Molecular events impact systemic dissemination. Overexpression of eukaryotic initiation factor 4E (eIF4E) has been shown to predict worse clinical outcomes in breast cancer. Node-positive breast cancer patients were specifically studied to determine if eIF4E elevation increases risk for systemic dissemination. STUDY DESIGN: Two hundred two node-positive breast cancer patients were prospectively accrued and treated with standardized treatment and surveillance protocol. Tumor eIF4E protein level was quantified by Western blots as x-fold over benign samples from noncancer patients. Primary end point was systemic metastasis. RESULTS: Systemic recurrence was detected in 22.2% of the low eIF4E group, 27.3% of the intermediate group, and 49% of the high group, at a median follow-up of 47 months. A greater risk for systemic metastasis was seen in the high eIF4E group compared with the low group (log-rank test, p = 0.0084). Patients in the high eIF4E group had a 1.5-fold (hazard ratio = 1.52; 95% CI, 1.07-2.17; p = 0.0206) higher risk for systemic metastasis than the low group. Sixty percent of the patients with high eIF4E were observed to have metastasis to multiple sites, compared with 50% in the intermediate group, and 14.5% in the low group (p = 0.02, Fisher's exact test). When patients were segregated based on nodal classification (N1, N2, and N3), eIF4E overexpression continued to be a predictor for systemic dissemination in patients with N1 disease. CONCLUSIONS: High eIF4E is correlated with an increased risk for systemic metastasis in node-positive breast cancer patients. High eIF4E overexpression was associated with a higher incidence of metastasis to multiple sites. Therefore, high eIF4E overexpression appears to be a marker for molecular events that increases risk for systemic dissemination.
BACKGROUND: Molecular events impact systemic dissemination. Overexpression of eukaryotic initiation factor 4E (eIF4E) has been shown to predict worse clinical outcomes in breast cancer. Node-positive breast cancerpatients were specifically studied to determine if eIF4E elevation increases risk for systemic dissemination. STUDY DESIGN: Two hundred two node-positive breast cancerpatients were prospectively accrued and treated with standardized treatment and surveillance protocol. Tumor eIF4E protein level was quantified by Western blots as x-fold over benign samples from noncancer patients. Primary end point was systemic metastasis. RESULTS: Systemic recurrence was detected in 22.2% of the low eIF4E group, 27.3% of the intermediate group, and 49% of the high group, at a median follow-up of 47 months. A greater risk for systemic metastasis was seen in the high eIF4E group compared with the low group (log-rank test, p = 0.0084). Patients in the high eIF4E group had a 1.5-fold (hazard ratio = 1.52; 95% CI, 1.07-2.17; p = 0.0206) higher risk for systemic metastasis than the low group. Sixty percent of the patients with high eIF4E were observed to have metastasis to multiple sites, compared with 50% in the intermediate group, and 14.5% in the low group (p = 0.02, Fisher's exact test). When patients were segregated based on nodal classification (N1, N2, and N3), eIF4E overexpression continued to be a predictor for systemic dissemination in patients with N1 disease. CONCLUSIONS: High eIF4E is correlated with an increased risk for systemic metastasis in node-positive breast cancerpatients. High eIF4E overexpression was associated with a higher incidence of metastasis to multiple sites. Therefore, high eIF4E overexpression appears to be a marker for molecular events that increases risk for systemic dissemination.
Authors: E P Bastos; H Brentani; C A B Pereira; A Polpo; L Lima; R D Puga; F S Pasini; C A B T Osorio; R A Roela; M I Achatz; A P Trapé; A M Gonzalez-Angulo; M M Brentani Journal: PLoS One Date: 2016-05-06 Impact factor: 3.240
Authors: Richard E Kast; Nicolas Skuli; Samuel Cos; Georg Karpel-Massler; Yusuke Shiozawa; Ran Goshen; Marc-Eric Halatsch Journal: Breast Cancer (Dove Med Press) Date: 2017-07-11