Independent Prognostic Indicator For Disease-free Survival Research Articles

Treatment, Prognostic Markers, and Survival in Thymic Neuroendocrine Tumors, with Special Reference to Temozolomide-Based Chemotherapy.

Thymic neuroendocrine tumors (Th-NETs) are rare and aggressive, with a scarcity of research on predicting patient prognosis. Our study aimed to assess the impact of prognostic markers and temozolomide (TMZ)-based chemotherapy on survival in Th-NETs. We retrospectively reviewed the medical records of patients diagnosed with Th-NETs between 2013 and 2023 at our institution. We collected clinicopathological data, including tumor pathological grading, staging, serum concentrations of neuron-specific enolase (NSE) and pro-gastrin-releasing peptide, levels of inflammatory factors, and expression of oxygen 6-methylguanine-DNA methyltransferase (MGMT). Treatment details (such as surgery and chemotherapy) and survival outcomes were also documented. A total of 32 patients were included in our study after excluding those without complete available information. The median progression-free survival (PFS) was 12.5 months (95%CI, 8-16 months) for 19 patients who received TMZ-based chemotherapy. Twenty-one patients underwent surgery as the primary treatment, demonstrating a median disease-free survival (DFS) of 51.0 months. The inflammatory factor neutrophil-to-lymphocyte ratio (NLR) was an independent prognostic indicator of DFS in postoperative patients and PFS in TMZ-treated patients. The overall 3-, 5-, and 10-year survival rates were 86.6%, 69.5%, and 33.8%, respectively. Ki67 level exceeding 10% (p = 0.048) and absence of surgical resection (p = 0.003) were significantly associated with worse overall survival (OS). Surgical treatment was currently the primary method for treating Th-NETs, and postoperative adjuvant therapy was an essential consideration for specific patient cohorts. Despite widespread positive MGMT expression, TMZ-based chemotherapy showed promise. Some potential prognostic biomarkers such as NLR and NSE need more attention.

Development and validation of nomogram to predict overall survival and disease-free survival after surgical resection in elderly patients with hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is one of the common causes of tumor death in elderly patients. However, there is a lack of individualized prognostic predictors for elderly patients with HCC after surgery.MethodWe retrospectively analyzed HCC patients over 65 years old who underwent hepatectomy from 2015 to 2018, and randomly divided them into training cohort and validation cohort in a ratio of 3:1. Univariate Cox regression was used to screen the risk factors related to prognosis. Prognostic variables were further selected by least absolute shrinkage and selection operator regression model (LASSO) and multivariate Cox regression to identify the predictors of overall survival (OS) and disease-free survival (DFS). These indicators were then used to construct a predictive nomogram. The receiver operating characteristic curve (ROC curve), calibration curve, consistency index (C-index) and decision analysis curve (DCA) were used to test the predictive value of these independent prognostic indicators.ResultA total of 188 elderly HCC patients who underwent hepatectomy were enrolled in this study. The independent prognostic indicators of OS included albumin (ALB), cancer embolus, blood loss, viral hepatitis B, total bilirubin (TB), microvascular invasion, overweight, and major resection. The independent prognostic indicators of DFS included major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion. In the training cohort, the ROC curve showed that the predictive values of these indicators for OS and DFS were 0.827 and 0.739, respectively, while in the validation cohort, they were 0.798 and 0.694. The calibration curve nomogram exhibited good prediction for 1-year, 2-year, and 3-year OS and DFS. Moreover, the nomogram models exhibited superior performance compared to the T-staging suggested by C-index and DCA.ConclusionThe nomogram established in this study demonstrate commendable predictive efficacy for OS and DFS in elderly patients with HCC after hepatectomy.Core Tip: The purpose of this retrospective study is to screen the risk factors of survival and recurrence in elderly patients with HCC after hepatectomy. The nomogram included cancer embolus, viral hepatitis B, overweight, major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion as predictors. The calibration curve of this nomogram was good, indicating credible predictive value and clinical feasibility.

Construction of immune score and its prognostic value in invasive lobular carcinoma of the breast using computational pathology analysis.

Previous studies have shown that high level of TILs in invasive lobular carcinoma (ILC) is associated with poor prognosis, contrary to that in TNBC and HER2-positive breast cancer. The densities of six immune cell markers and three immune checkpoints in the ILC microenvironment were detected by computational pathology analysis. Then, the LASSO cox regression model was used to construct an immune score (IS) and further evaluate its prognostic value. In our ILC cohort, the low density of CD4, CD8, CD20, CD56, CD68, FOXP3, PD-1, and PD-L1 had significantly longer disease-free survival (DFS) and overall survival (OS); however, the low density of CTLA-4 was associated with shorter DFS and OS. Based on this, an IS was constructed, and patients with low-IS had significantly prolonged DFS (p < 0.0001) and OS (p < 0.0001). Multivariate analysis revealed that IS was an independent prognostic indicator for DFS and OS. Further analysis showed that IS may increase the prognostic value of TNM stage. We further explored the prognostic role of CD68 and FOXP3 in the transcriptional level and the corresponding ISm in the METABRIC dataset, and found that low proportion of CD68 and FOXP3 and their ISm were associated with longer OS, and ISm was also an independent prognostic factor for OS. IS was a promising biomarker to distinguish the prognosis in ILC patients.

Prognostic role of pre-treatment serum ALB in Patients with oropharyngeal cancer: A retrospective cohort study.

The morbidity of oropharyngeal cancer (OPC) is continuing to rise in numerous developed countries. An accurate prognostic assessment is needed to evaluate the malignant degree or risk classification to optimize treatment. Albumin (ALB) as an independent prognostic indicator of cancer survival has been established in previous studies. This study investigated the prognostic value of pre-treatment serum ALB in OPC patients. The clinicopathological data of 246 patients diagnosed with OPC from 2010 to 2019 were analyzed retrospectively. Analyze the relationship between ALB and clinicopathological characteristics of patients. The optimal cut-off values for ALB were determined via Cutoff Finder (Method for cutoff determination: Survival: significance (log-rank test)). To determine the independent prognostic factors, the Cox proportional hazards model was used to perform univariate and multivariate analyses of the serum ALB levels related to overall survival (OS) and disease-free survival (DFS). The optimal cut-off point for ALB was 39.15 g/L determined via Cutoff Finder. Serum ALB levels were significantly associated with age (P=0.047), Presence of comorbidity (P=0.009), Charlson score index (P=0.007), Hemoglobin (P<0.001), Neutrophil to Lymphocyte Ratio (P=0.002), Albumin-To-Alkaline Phosphatase Ratio (P<0.001), Alkaline phosphatase (P=0.005), T stage (P=0.016), and HPV status (P=0.002). In the univariate and multivariate analyses, ALB was found to be an independent prognostic indicator for DFS (HR =0.39, 95% CI:0.23-0.66, P=0.000) and OS (HR =0.46, 95% CI: 0.25-0.83, P=0.01) in OPC patients. Pre-treatment serum ALB could serve as a valuable prognostic biomarker for the prognostic stratification of OPC patients.

The expression of Eps15 homology domain 1 is negatively correlated with disease-free survival and overall survival of osteosarcoma patients

BackgroundOsteosarcoma was locally aggressive and frequently metastasizes to the lung. However, the etiology of osteosarcoma was unknown. Thus, exploring the mechanisms behind the occurrence of osteosarcoma was important for its prediction and prevention. To investigate the usefulness of mammalian Eps15 homology domain 1 (EHD1) as a prognostic marker for osteosarcoma, the expression of EHD1 in 57 osteosarcoma patients was measured using immunohistochemistry techniques and correlated with the clinicopathological features of patients.MethodsCorrelations of EHD1 expression levels with clinicopathological features of patients were assessed using the Pearson χ2 test for categorical variables and the Student t test for continuous variables. Cumulative disease-free survival (DFS) curves and overall survival (OS) curves were plotted using the Kaplan–Meier method, and the relationship between each of the variables and survival was assessed by log-rank tests using univariate analysis. Subsequently, the parameters were tested using the multivariate Cox proportional hazards model, which was used to identify independent variables for predicting survival. EHD1 expression [P = 0.020; HR, 5.582; 95% confidence intervals (CI), 1.314–23.72] was an independent prognostic indicator of DFS in osteosarcoma patients; tumor size and EHD1 expression of osteosarcomas were independent prognostic indicators of OS in osteosarcoma patients.ResultsEHD1 protein expression was a positive expression in examined tumor tissues. The median OS time of patients with high expression of EHD1 was 46.8 months (95% CI, 29.8–63.8 months), and the median OS time of patients with low expression of EHD1 was 58.8 months (95% CI, 31.6–86.0 months). The prognosis for patients with low expression of EHD1 in osteosarcomas was significantly better than that for patients with high expression of EHD1 (log-rank test, P = 0.019).ConclusionThe expression of EHD1 was negatively correlated with DFS and OS of osteosarcoma patients; therefore, the expression of EHD1 is a prognostic marker for prediction and prevention of osteosarcomas.

Prognostic significance of tumor-infiltrating lymphocytes in nondisseminated nasopharyngeal carcinoma: A large-scale cohort study.

The American Joint Committee on Cancer (AJCC) staging system is inadequate for an accurate prognosis in nasopharyngeal carcinoma (NPC). Thus, new biomarkers are under intense investigation. Here, we investigated whether the density of TILs could predict prognosis in NPC. First, we used 1490 cases of nasopharyngeal carcinoma samples from two independent cohorts to evaluate the density and distribution of tumor-infiltrating lymphocytes (TILs). Second, in one cohort, we assessed associations between TILs and clinical outcomes in 593 randomly selected samples (defined as the training set) and validated findings in the remaining 593 samples (defined as the validation set). Furthermore, we confirmed the prognostic value of TILs in a second independent cohort of 304 cases (defined as the independent set). Based on multivariable Cox regression analysis, we also established an effective prognostic nomogram including TILs to improve accuracy in predicting disease-free survival (DFS) for patients with nondisseminated NPC. We found that high TILs in the training set were significantly associated with favorable DFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.58, p < 0.001], overall survival (OS, HR 0.42, 95% CI 0.27-0.64, p < 0.001), distant metastasis-free survival (DMFS, HR 0.37, 95% CI 0.23-0.58, p < 0.001) and local-regional recurrent free survival (LRRFS, HR 0.43, 95% CI 0.25-0.73, p = 0.002). Multivariate analysis showed that TILs are an independent prognostic indicator for DFS in all cohorts. In summary, this study indicated that TILs may reflect the immunological heterogeneity of NPC and could represent a new prognostic biomarker.

Clinical implications of pretreatment inflammatory biomarkers as independent prognostic indicators in prostate cancer.

Research on the relationship between inflammatory biomarkers and malignant tumors has become a hotspot. Many studies have demonstrated that neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) could act as independent prognostic indicators for several solid tumors. This study aimed to evaluate the clinical implications of pretreatment inflammatory biomarkers, including NLR, PLR, and RDW as independent prognostic indicators in prostate cancer (PCa). A total of 226 PCa patients who were diagnosed at our institution from 2011 to 2016 were analyzed retrospectively. We compared the clinicopathological features, survival curves, and prognosis of the PCa patients between the high and low groups according to the cutoffs of NLR, PLR, and RDW. The pretreatment NLR, PLR, and RDW values were significantly higher in the patients with PCa than those in the controls (P<.05). Increased NLR and PLR values were significantly associated with high risk of progression, including higher Gleason scores, cell proliferation antigen 67 (Ki-67) indexes, and prostate-specific antigen (PSA) levels (P<.05), whereas an elevated RDW was only associated with an older age. An increased NLR was correlated with both overall survival (OS) (P=.025) and disease-free survival (DFS) (P=.017). In addition, a higher PLR only showed a significantly worse DFS (P=.040). Pretreatment NLR was an independent prognostic indicator of DFS. The pretreatment NLR and PLR might be beneficial to predict the progression and prognosis of PCa. Furthermore, NLR was more effective than PLR acting as an independent prognostic indicator for PCa.

N-RAS expression in patients with salivary adenoid cystic carcinoma: association with clinicopathologic features and prognosis

The aim of this study was to investigate N-RAS expression in patients with salivary adenoid cystic carcinoma (SACC) and to analyze its association with clinicopathologic features and prognosis. We determined N-RAS expression in SACC tumors via immunohistochemistry and evaluated the association between N-RAS expression and clinicopathologic variables. The disease-free survival (DFS) curves were plotted by using the Kaplan-Meier method. The parameters of prognostic significance found by univariate analysis were tested by a multivariate Cox regression model. N-RAS expression was detected in 61 of 72 SACC tumor samples (84.7%). In univariate analyses, N-RAS expression was associated with clinical stage, tumor size, adjacent tissue invasion, and distant metastasis. N-RAS expression was associated with DFS in univariate analysis; however, in multivariate analysis, N-RAS was not an independent prognostic indicator, but clinical stage (0.04) and histologic subtype (0.02) were statistically significant. Our data suggest that N-RAS was overexpressed in SACC tissues, but was not an independent prognostic indicator of DFS. Only clinical stage and histologic subtype were prognostic indicators of DFS.

Low preoperative albumin-globulin score predicts favorable survival in esophageal squamous cell carcinoma.

This study retrospectively investigated the prognostic significance of the preoperative albumin-globulin score (AGS) and albumin/globulin ratio (AGR) in esophageal squamous cell carcinoma (ESCC). A cohort of 458 newly diagnosed ESCC patients who underwent radical esophagectomy in Sun Yat-sen University Cancer Center (Guangzhou, China) between January 2006 and December 2010 were selected into this study. The optimal cut-off value was identified to be 45.6 g/L, 26.9 g/L and 1.30 for albumin (ALB), globulin (GLB) and AGR in terms of survival, respectively. Patients with low ALB levels (< 45.6 g/L) and high GLB levels (≥ 26.9 g/L) were assigned an AGS of 2, those with only one of the two abnormalities were assigned an AGS of 1, and those with neither of the two abnormalities were assigned an AGS of 0. Univariate survival analysis showed that low AGS (0) was significantly associated with favorable disease free survival (DFS) [hazard ratio (HR), 0.635; 95% confidence interval (CI), 0.441–0.914; P = 0.015] and overall survival (OS) (HR, 0.578; 95% CI, 0.387–0.862; P = 0.007), and it remained an independent predictor for OS (HR, 0.630; 95% CI, 0.418–0.952; P = 0.028), but not for DFS (HR, 0.697; 95% CI, 0.479–1.061; P = 0.060) in multivariate models. High AGR (≥ 1.30) was also correlated with favorable DFS (HR, 0.626; 95% CI, 0.430–0.910; P = 0.014) and OS (HR, 0.622; 95% CI, 0.422–0.916; P = 0.016) in univariate analysis, but it failed to be an independent prognostic indicator for DFS (HR, 0.730; 95% CI, 0.494–1.078; P = 0.114) or OS (HR, 0.759; 95% CI, 0.507–1.137; P = 0.181) by multivariate analysis. Low preoperative AGS could serve as a valuable and convenient biochemical marker to predict favorable long-term survival in ESCC patients.

High Levels of Nucleolar Spindle-Associated Protein and Reduced Levels of BRCA1 Expression Predict Poor Prognosis in Triple-Negative Breast Cancer.

PurposeNucleolar spindle-associated protein (NuSAP1) is an important mitosis-related protein, and aberrant NuSAP1 expression is associated with abnormal spindles and mitosis. This study investigated the prognostic value of NuSAP1 in breast cancer.MethodsTwo sets of tissue microarrays (TMAs) that included samples from 450 breast cancer patients were constructed, of which 250 patients were training set and the other 200 patients were validation set. Immunohistochemical staining was performed to determine the NuSAP1 levels. A Kaplan-Meier analysis was used to estimate the prognostic value of NuSAP1 in breast cancer. A stepwise Cox analysis was performed to construct a risk-prediction model for triple-negative breast cancer (TNBC). All statistical analysis was performed with SPSS software.ResultsThere were 108 (43.5%) and 88 (44.0%) patients expressed NuSAP1 in the training set and validation set respectively. High levels of NuSAP1 expression were related to poor disease-free survival (DFS) in both training (P = 0.028) and validation (P = 0.006) cohorts, particularly in TNBC. With combination of two cohorts, both NuSAP1 (HR = 4.136, 95% CI: 1.956–8.747, P < 0.001) and BRCA1 (HR = 0.383, 95% CI: 0.160–0.915, P = 0.031) were independent prognostic indicators of DFS in TNBC. A receiver operating characteristic (ROC) analysis revealed that the combination of NuSAP1 and BRCA1 significantly improved the prognostic power compared with the traditional model (0.778 versus 0.612, P < 0.001).ConclusionsOur study confirms the prognostic value of NuSAP1 in breast cancer. The combination of NuSAP1 and BRCA1 could improve the DFS prediction accuracy in TNBC.

Increased Expression of Eps15 Homology Domain 1 is Associated with Poor Prognosis in Resected Small Cell Lung Cancer.

One of the great challenges of small cell lung cancer (SCLC) treatment is identifying patients at high risk for recurrence after surgical resection and chemotherapy. We examined Eps15 homology domain 1 (EHD1) protein expression in paraffin sections of 85 resected SCLC tissues, metastatic lymph nodes and normal bronchial epithelial tissues using immunohistochemistry to study the correlation between EHD1 expression and patient clinicopathological features. Within these variables, disease free survival (DFS) analyzed by the log-rank test was constructed using the multivariate Cox proportional hazards regression model and Kaplan-Meier analysis. Immunohistochemistry results showed that EHD1 protein was significantly increased in SCLC tissues compared with normal tissues (P < 0.001). Moreover, EHD1 expression was positively correlated with tumor size (P = 0.019). Multivariate Cox proportional hazards model analysis showed that EHD1 expression (P = 0.047; HR, 1.869; 95% CI, 1.008-3.466) and American Joint Committee on Cancer (AJCC) status (P < 0.001; HR, 1.412; 95% CI, 1.165-1.711) were independent prognostic indicators of DFS. In conclusion, these data demonstrated a remarkable correlation between the cytoplasmic expression of EHD1 protein and adverse prognosis in patients receiving early-stage cisplatin treatment for resected SCLC.

MACC1 overexpression predicts a poor prognosis for non-small cell lung cancer

The expression of metastasis-associated in colon cancer-1 (MACC1) in non-small cell lung cancer (NSCLC) and its association with pathological characteristics and prognosis for NSCLC patients were investigated retrospectively. The expression of MACC1 was evaluated through immunohistochemical staining of tissue microarrays from 180 samples of resected lung cancer tissues and adjacent normal lung tissues. MACC1 protein and mRNA expression were also examined from lung cancer cell lines with different metastatic potentials, 28 pairs of samples of resected fresh non-small cell lung cancer tissues, and adjacent normal lung tissues. Immunohistochemical staining of tissue microarrays showed that MACC1 was located in the cytoplasm. In addition, the expression of MACC1 protein in NSCLC was significantly higher compared to adjacent normal tissues (P < 0.001). The expression of MACC1 was positively associated with differentiation grade (P = 0.020), postoperative pathological TNM stage (P = 0.033), and lymph node metastasis (P = 0.028). Disease-free survival (DFS) and overall survival (OS) for the high MACC1 expression group were lower than the low expression group; univariate and multivariate regression analyses showed that MACC1 was an independent prognostic indicator for DFS (HR 3.124, P = 0.01) and OS (HR 2.905, P = 0.01) in NSCLC patients. The expression of MACC1 protein and mRNA was also upregulated in highly metastatic human lung cancer. In conclusion, the overexpression of MACC1 protein and mRNA may represent a potentially useful biomarker for the prognosis of NSCLC patients and might be involved in progression of NSCLC.

Molecular Signatures of Localized Clear Cell Renal Cell Carcinoma to Predict Disease-Free Survival after Nephrectomy

To identify the molecular signature of localized (N0M0) clear cell renal cell carcinoma (RCC) and assess its ability to predict outcome. Clinical characteristics and pathologic records of 170 patients with localized clear cell RCC who underwent nephrectomy were reviewed. Immunohistochemical analysis was done on a tissue microarray of all primary tumors using a kidney cancer-related panel of protein markers, which included CAIX, CAXII, CXCR3, gelsolin, Ki-67, vimentin, EpCAM, p21, p27, p53, pS6, PTEN, HIF-1alpha, pAkt, VEGF-A, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2, and VEGFR-3. Associations with disease-free survival (DFS) were evaluated with Cox models, and a concordance index assessed prognostic accuracy. Median follow-up was 7.1 years. The final multivariate Cox model determined T classification, Eastern Cooperative Oncology Group performance status, and five molecular markers (Ki-67, p53, endothelial VEGFR-1, epithelial VEGFR-1, and epithelial VEGF-D) to be independent prognostic indicators of DFS. The molecular signature based on these markers predicted DFS with an accuracy of 0.838, an improvement over T classification of 0.746, and the University of California-Los Angeles Integrated Staging System of 0.780. A constructed nomogram combined the molecular, clinical, and pathologic factors and approached a concordance index of 0.904. A molecular signature consisting of five molecular markers (Ki-67, p53, endothelial VEGFR-1, epithelial VEGFR-1, and epithelial VEGF-D) can predict DFS for localized clear cell RCC. The prognostic ability of the signature and nomogram may be superior to clinical and pathologic factors alone and may identify a subset of localized patients with aggressive clinical behavior. Independent, external validation of the nomogram is required.

Tumor metabolism, blood flow changes, and prognosis by positron emission tomography: A prospective cohort of locally advanced breast cancer patients

506 Background: Breast cancer patients with locally advanced tumors receive preoperative chemotherapy to provide early systemic treatment and assess in-vivo tumor response. Positron emission tomography (PET) has been used to follow tumor response to therapy, as pathologic response is predictive of patient outcome. We evaluated the prognostic utility of serial quantitative PET tumor blood flow (BF) and metabolism measurements. Methods: Fifty-five women with a primary diagnosis of locally advanced breast carcinoma (LABC) underwent dynamic [18F]-FDG and [15O]-water PET scans prior to and at midpoint of neoadjuvant chemotherapy. The FDG metabolic rate (MRFDG), transport (K1), and flux (Ki) parameters were calculated, and tumor blood flow was estimated from the [15O]-water study. Associations between tumor BF and MRFDG measurements and disease-free survival (DFS) and overall survival (OS) were evaluated using the Cox proportional hazards model. Results: Patients that had an increase in BF and K1, from baseline to mid-therapy measurements, had elevated recurrence and mortality risks compared to patients that had reductions in BF and MRFDG values. In multivariate analysis, changes in BF and K1 remained independent prognostic indicators of DFS and OS survival. Conclusions: PET measurements of tumor response prior to completion of neoadjuvant chemotherapy were predictive of patient outcome. Patients that failed to have a decline in BF and K1 experienced higher risks of recurrence and mortality that was largely independent of clinical tumor characteristics assessed in this study. These results suggest that tumor perfusion, measured directly by [15O]-water or indirectly by dynamic FDG PET, is highly predictive of outcome in neoadjuvantly treated breast cancer. No significant financial relationships to disclose.

C-erbB-2 oncoprotein overexpression identifies a subgroup of estrogen receptor positive (ER +) breast cancer patients with poor prognosis

To investigate the predictive value of c-erbB-2 oncoprotein expression as compared with established histopathological and cytometric indicators of disease evolution in breast carcinoma. A short-term retrospective study was conducted on a series of 306 breast cancer patients. Classic prognostic factors included tumour size, nodal involvement, histological grading, and hormone receptor status. Flow cytometric DNA ploidy and S-phase fraction (SPF) were also assessed. A Cox proportional hazards regression model was used for multivariate statistical analysis. c-erbB-2 overexpression was present in 43 out of 295 (14.6%) tumours, and showed a statistically significant correlation with high histological grade, DNA aneuploidy, high SPF and lack of estrogen receptors (ER). Univariate analysis revealed its association with worse disease-free survival (DFS) and overall survival (OS). The combined evaluation of c-erbB-2 with ploidy and SPF defines a variable (P + S + c) that showed a significant correlation with disease outcome. By multivariate analysis, only nodal status (P < 0.001) and P + S + c subgrouping (group 2: P = 0.002; group 3: P = 0.001) in relation to DFS, and nodal status (P = 0.001) and DNA ploidy (P = 0.006) in relation to OS, retained independent prognostic significance. Subset analyses showed that cytometric parameters, P + S + c subgrouping and hormone receptors were significantly correlated with disease outcome in node-positive patients, whereas in node-negative subgroup no prognostic indicators were found. c-erbB-2 overexpression exhibited a trend in node-positive breast cancer (DFS: P = 0.068; OS: P = 0.086), and significant correlation with poor clinical evolution in ER positive patients (DFS: P = 0.015; OS: P = 0.004), mostly receiving tamoxifen. c-erbB-2 is an independent prognostic indicator of DFS when evaluated in conjunction with ploidy and SPE. It also seems to predict response to tamoxifen therapy, by identifying a subgroup of ER positive (ER+) breast cancer patients with poor prognosis.