Hounsfield Units Predict Survival of Patients With Estrogen Receptor-Positive and Human Epithelial Growth Factor Receptor 2-Negative Breast Cancer.

BACKGROUNDS: Tumor vascularity plays a fundamental role in cancer progression, including breast cancer. This study aimed to elucidate tumor vascularity and its impact on patient survival in the context of breast cancer subtypes using Hounsfield units (HU) on contrast-enhanced computed tomography (CT). MATERIALS AND METHODS: Patients with early-stage breast cancer who completed planned treatment between 2003 and 2013 were retrospectively assessed. RESULTS: The final cohort comprised 440 patients. Of the 440 patients, 262 had estrogen receptor (ER)-positive disease and 119 had human epidermal growth factor receptor 2 (HER2)-overexpressing disease. The tumor-to-aorta ratio of Hounsfield units (TAR) was related to significantly worse recurrence-free interval (RFI) (P < .001) and overall survival (OS) (P < .001) in patients with TAR > 0.33 for RFI and > 0.35 for OS than their counterparts. In the subgroup analysis, the survival disadvantage was limited only to patients with ER-positive and HER2-negative disease (P < .001 for both RFI and OS). CONCLUSION: This study showed that TAR, which reflects tumor vascularity, was significantly related to patients' RFI and OS, suggesting its capacity as a feasible biomarker. This study also showed that TAR was associated with the survival in patients with ER-positive and HER2-negative disease.

Usefulness of Hounsfield Units and the Serum Neutrophil-to-Lymphocyte Ratio as Prognostic Factors in Patients with Breast Cancer.

Breast cancer is a leading cause of death worldwide. Tumor vascularity and immune disturbances are hallmarks of cancer. This study aimed to investigate the reciprocal effect of tumor vascularity, assessed by the tumor-to-aorta ratio (TAR) of Hounsfield units (HU) on computed tomography (CT), and host immunity, represented by the serum neutrophil-to-lymphocyte ratio (NLR) from peripheral, complete blood cell counts and its impact on patient survival. Female patients with breast cancer who received primary treatment between 2003 and 2018 at Wonju Severance Hospital, Korea, were included. The final cohort included 740 patients with a mean age of 54.3 ± 11.3 (22−89) years. The TAR was 0.347 ± 0.108 (range, 0.062−1.114) and the NLR was 2.29 ± 1.53 (0.61−10.47). The cut-off value for the TAR and NLR were 0.27 and 1.61, respectively. The patients with a TAR > 0.27 showed a poor recurrence free-interval (RFI) only when their NLR was larger than 1.61, and vice versa. The patients showed worse RFI when they had both high TAR and NLR. Our results suggest a dynamic reciprocal communication between tumor vascularity and systemic immunity.

Neutrophil to Lymphocyte Ratio after Treatment Completion as a Potential Predictor of Survival in Patients with Triple-Negative Breast Cancer.

PURPOSE: Triple-negative breast cancer (TNBC) has been associated with worse prognosis, and biomarkers are needed to identify high-risk patients who may benefit from clinical trials or escalated treatment after completion of standard treatment. We aimed to assess whether the post-treatment neutrophil-to-lymphocyte ratio (NLR) can reflect patient prognosis and determine the follow-up period that can provide the most feasible data. METHODS: In this retrospective analysis involving patients with TNBC, clinicopathological data, including those on peripheral complete blood cell count, were collected. The prognostic powers of serial NLRs obtained at baseline and after treatment completion were compared. Kaplan-Meier curves were generated to compare the overall survival (OS) and distant disease-free survival (DDFS). RESULTS: In total, 210 patients were enrolled. Forty-three (20.5%) events were detected. Two-thirds of the events (29/43) were related to breast cancer. Most recurrent breast cancer-related diseases (27/29) were detected within 5 years of the initial diagnosis. In contrast, half of the events due to secondary malignancies or non-breast-related diseases (7/14) occurred 5 years after the initial diagnosis. Comparison of the prognostic performance of NLRs at baseline and at 6, 12, and 24 months after treatment completion revealed the strongest prognostic performance at 6 months after treatment completion (area under the curve = 0.745). The high NLR group (NLR >2.47) showed worse OS (p = 0.006) and DDFS (p < 0.001) than low NLR group. CONCLUSION: Elevated post-treatment NLR was significantly associated with worse survival in patients with TNBC. We believe that it can be a useful surrogate marker for identifying high-risk patients with TNBC.

Increasing Mortality in Korean Patients With Breast Cancer: High Mortality Rate in Elderly Breast Cancer Population Due to Suboptimal Treatment and Other Diseases.

BACKGROUND: The incidence of breast cancer in Asia, including Korea, has rapidly increased. Each country has shown different clinical features. This study presents a comprehensive understanding of breast cancer in different age groups in Korea and determines potential measures for improving patient survival. METHODS: Patients diagnosed with invasive breast cancer stages I to III with available clinicopathologic and follow-up data were included in the study. Kaplan-Meier survival graphs were generated for each group and compared using log-rank test. The hazard ratio for each risk factor was calculated using the Cox regression model and the 95% confidence interval. RESULTS: The final cohort included 833 patients with a mean age of 51.3±11.3 years (range, 22-89 years), and 191 (22.9%) of them were aged >60 years. Patients aged ≥60 years had worse overall survival (OS) and distant disease-free survival than those aged <60 years. Although no difference was observed in the tumor biology, elderly patients showed significant differences in practice patterns: they tended to undergo mastectomy (40.2% vs 62.8%, P<0.001), did not receive the standard chemotherapy (88.4% vs 69.3%, P < 0.001), and had a higher risk of developing second primary cancer or diseases other than breast cancer (1.2% vs 6.8%, P < 0.001), which significantly correlated with poor survival in elderly patients. CONCLUSION: Less-than-the-standard treatment of care or development of a second primary disease resulted in poor prognosis in elderly patients in Korea. A multi-institutional and multinational study is warranted to elucidate the clinical features of breast cancer in Asian patients.

Changes in neutrophil to lymphocyte ratio (NLR) during neoadjuvant treatment correlated with patients' survival.

INTRODUCTION: Neoadjuvant treatment has been widely used for patients with advanced breast cancer, and pathological complete response (pCR) has been proposed as a surrogate marker. However, more than 50% of patients will not achieve pCR and an appropriate, practical prognostic marker is required for these patients. MATERIALS AND METHODS: A retrospective analysis of patients treated with neoadjuvant treatment for stage I-III disease was performed. Clinicopathological data including the neutrophil-to-lymphocyte ratio (NLR) were collected. NLRs were collected serially according to the treatment schedule. Changes in NLRs were calculated, of which the performance capacity as a prognostic factor was evaluated, and a Kaplan-Meier plot was developed and compared with the log rank test RESULTS: Changes in NLRs of each time points of 148 patients were used to assess performance capacity as a prognostic factor for invasive disease-free survival (IDFS), overall survival (OS) and distant disease-free survival (DDFS), and that of shortly prior to the third cycle treatment showed statistical significance. With a cut off value of 0.1258, patients could be divided into high- and low-risk of invasive disease recurrence. Kaplan-Meier curves were developed and the log rank test showed that patients in high-risk group after 2 cycles of neoadjuvant treatment were significantly correlated with worse survival outcomes than those in low-risk group. CONCLUSION: Changes in NLRs after neoadjuvant treatment showed statistically significant correlation with patient survival and could categorize patients into high- and low-risk groups. Larger, prospectively designed clinical trials are required to substantiate findings of this study.

Prediction of late recurrence in patients with breast cancer: elevated neutrophil to lymphocyte ratio (NLR) at 5 years after diagnosis and late recurrence.

BACKGROUND: Late recurrence accounts for nearly half of the recurrences in estrogen receptor (ER)-positive breast cancer and decreases post-recurrence survival in patients with ER-negative breast cancer. Clinicopathological factors and multigene assays have been used for various purposes but their prognostic capacity for late recurrence was limited. This study aimed to determine whether neutrophil to lymphocyte ratio (NLR) taken after primary treatment can be a feasible prognostic factor for late recurrence. METHODS: Patients who were diagnosed with primary breast cancer and completed planned treatment were enrolled; data were retrospectively collected from the Wonju Severance Hospital database of Yonsei University. RESULTS: 496 patients completed planned treatment for their primary breast cancer. 385 were disease free after 5 years of the primary diagnosis and 330 were enrolled for second-look NLR analysis. NLR analysis performed approximately 5 years after the primary diagnosis categorized patients into high and low risk of late recurrence with p < 0.001 and an elevated NLR was found as an independent risk factor for late recurrence (HR 1.448, CI 1.168-1.795, p < 0.001). CONCLUSION: A clinically valid biomarker to determine late recurrence is urgently needed to prevent patients from treatment extension with little benefit. Elevated NLR is found as an independent prognostic factor for late recurrence and could be utilized as a reliable, easily accessible, and cost-effective test.

Longer survival in patients with breast cancer with cyclin d1 over-expression after tumor recurrence: longer, but occupied with disease.

PURPOSE: The effect of cyclin D1 overexpression on breast cancer outcomes and prognosis is controversial, even though amplification of the cyclin D1 gene, CCND1, has been shown to be associated with early relapse and poor prognosis. In this study, we examined the relationship between cyclin D1 overexpression and disease-specific survival (DSS). We also analyzed survival in patients who experienced recurrence. METHODS: We retrospectively analyzed data from patients diagnosed with ductal carcinoma between April 2005 and December 2010. We examined clinicopathologic factors associated with cyclin D1 overexpression and analyzed the influence of cyclin D1 on recurrence-free survival and DSS. RESULTS: We identified 236 patients diagnosed with primary breast cancer who completed all phases of their primary treatment. Cyclin D1 overexpression was significantly associated with longer DSS (5-year DSS, 89.9% in patients without cyclin D1 overexpression vs. 98.9% in patients with cyclin D1 overexpression; p=0.008). Multivariate analysis also found that patients with cyclin D1 overexpressing tumors had significantly longer disease-specific survival than patients whose tumors did not overexpress cyclin D1, with a hazard ratio for disease-specific mortality of 7.97 (1.17-54.22, p=0.034). However, in the group of patients who experienced recurrence, cyclin D1 overexpression was not significantly associated with recurrence-free survival. Cyclin D1 overexpression was significantly associated with increased survival after disease recurrence, indicating that cyclin D1 overexpression might be indicative of more indolent disease progression after metastasis. CONCLUSION: Cyclin D1 overexpression is associated with longer DSS, but not recurrence-free survival, in patients with breast cancer. Longer postrecurrence survival could explain the apparent inconsistency between DSS and recurrence-free survival. Patients with cyclin D1-overexpressing tumors survive longer, but with metastatic disease after recurrence. This information should spark the urgent development of tailored therapies to cure these patients.

Usefulness of pretreatment neutrophil to lymphocyte ratio in predicting disease-specific survival in breast cancer patients.

PURPOSE: The purpose of this study was to investigate the prognostic impact of pretreatment neutrophil to lymphocyte ratio (NLR) on breast cancer in view of disease-specific survival and the intrinsic subtype. METHODS: We retrospectively studied patients diagnosed with primary breast cancer that had completed all phases of primary treatment from 2000 to 2010. The association between pretreatment NLR and disease-specific survival was analyzed. RESULTS: A total of 442 patients were eligible for analysis. Patients with higher NLR (2.5 ≤NLR) showed significantly lower disease-specific survival rate than those with lower NLR (NLR <2.5). Higher NLR along with negative estrogen receptor status and positive nodal status were independently correlated with poor prognosis, with hazard ratio 4.08 (95% confidence interval [CI], 1.62-10.28), 9.93 (95% CI, 3.51-28.13), and 11.23 (95% CI, 3.34-37.83), respectively. Luminal A subtype was the only intrinsic subtype in which higher NLR patients showed significantly poor prognosis (87.7% vs. 96.7%, p=0.009). CONCLUSION: Patients with an elevated pretreatment NLR showed poorer disease-specific survival than patients without elevated NLR, most evident in the luminal A subtype. Further validation and a feasibility study are required before it can be considered for clinical use.

The diagnostic values of preoperative laboratory markers in children with complicated appendicitis.

PURPOSE: Accurate diagnosis and optimal management of acute appendicitis, despite being the most common surgical emergency encountered in emergency departments, is often delayed in pediatric patients due to nonspecific symptoms and communication barriers, often leading to more complicated cases. The aim of this study is to investigate the diagnostic significance of common laboratory markers. METHODS: A total of 421 patients aged 15 and younger underwent surgical treatment for acute appendicitis. We conducted a retrospective analysis for white blood cell (WBC), C-reactive protein (CRP) and bilirubin. All patients were classified into simple or complicated appendicitis groups based on postoperative histology. RESULTS: The mean age of the patients in the complicated appendicitis group was younger than that in the simple group (P = 0.005). WBC, CRP and bilirubin levels were significantly higher in the complicated appendicitis group (P < 0.001, <0.001, 0.002). The relative risk for complicated appendicitis was calculated using age, WBC, CRP and bilirubin. Elevated CRP levels were associated with the highest risk for complicated appendicitis (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.38 to 4.65) followed by WBC (HR, 2.42; 95% CI, 1.07 to 5.46) and bilirubin (HR, 2.04; 95% CI, 1.09 to 3.82). The most sensitive markers for diagnosing complicated appendicitis were WBC (95.2%) and CRP (86.3%). Bilirubin levels showed the highest specificity at 74.8%. CONCLUSION: The risk of complicated appendicitis was significantly higher in patients younger than 10 years old. Preoperative WBC, CRP and bilirubin have clinical value in diagnosing complicated appendicitis with a HR of 2.0 to 2.5. Our results suggest that the utilization of WBC, CRP, and bilirubin can assist in the diagnosis of complicated appendicitis in pediatric patients, allowing prompt diagnosis and optimal management.