Prognostic role of derived neutrophil-to-lymphocyte ratio in surgical triple-negative breast cancer.
ABSTRACT: Introduction:The role of derived neutrophil-to-lymphocyte ratio (dNLR) in predicting the prognosis of patients with triple-negative breast cancer (TNBC) has not been well studied. Here, we attempted to investigate the significance of dNLR in predicting the prognosis of patients with surgical (nonmetastatic) TNBC. Methods:A total of 281 patients diagnosed with surgical TNBC in The First Affiliated Hospital of University of Science and Technology of China from February 2005 to March 2015 were retrospectively included in this study. Kaplan-Meier curve analysis was used to assess the disease-free survival (DFS) and overall survival (OS). We used Cox regression model to assess the prognostic significance of pretreatment dNLR and other clinicopathological parameters in TNBC patients. Results:The median DFS in TNBC patients who had low dNLR and high dNLR was 28.9 and 15.1 months (P<0.001), respectively, whereas the median OS in patients who had low dNLR and high dNLR was 71.2 and 42.3 months (P<0.001), respectively. In patients aged ?50 years and with invasive ductal carcinoma, a low dNLR predicted better DFS and OS compared with a high dNLR. Multivariate analysis demonstrated that the increased dNLR was a risk factor of poor DFS (HR=1.90, 95% CI: 1.52-2.46, P=0.007) and OS (HR=2.56, 95% CI: 1.69-3.58, P=0.001). Conclusion:Pretreatment dNLR is an independent factor of prognosis for TNBC patients, which potentially allows clinical doctors to improve outcomes of patients with high dNLR by treating with aggressive therapy, such as high-dose adjuvant chemotherapy and radiotherapy.
Project description:Considering the distinctive biology of triple-negative breast cancer (TNBC), this study aimed to identify TNBC-specific prognostic factors and determine the prognostic value of the Nottingham Prognostic Index (NPI) and its variant indices.A total of 233 patients with newly diagnosed stage I to III TNBC from 2003 to 2012 were reviewed. We retrospectively analyzed the patients' demographics, clinicopathologic parameters, treatment, and survival outcomes. The NPI was calculated as follows: tumor size (cm)×0.2+node status+Scarff-Bloom-Richardson (SBR) grade. The modified NPI (MNPI) was obtained by adding the modified SBR grade rather than the SBR grade.The median follow-up was 67.8 months. Five-year disease-free survival (DFS) and overall survival (OS) were 81.4% and 89.9%, respectively. Multivariate analyses showed that the MNPI was the most significant and common prognostic factor of DFS (p=0.001) and OS (p=0.019). Young age (?35 years) was also correlated with poor DFS (p=0.006). A recursive partitioning for establishing the prognostic model for DFS was performed based on the results of multivariate analysis. Patients with a low MNPI (?6.5) were stratified into the low-risk group (p<0.001), and patients with a high MNPI (>6.5) were subdivided into the intermediate (>35 years) and high-risk (?35 years) groups. Age was not a prognostic factor in patients with a low MNPI, whereas in patients with a high MNPI, it was the second key factor in subdividing patients according to prognosis (p=0.023).The MNPI could be used to stratify patients with stage I to III TNBC according to prognosis. It was the most important prognosticator for both DFS and OS. The prognostic significance of young age for DFS differed by MNPI.
Project description:BACKGROUND:Growing evidence has revealed that pretreatment C-reactive protein to albumin ratio (CAR) are associated with prognosis for patients with renal cell carcinoma (RCC). However, inconsistent findings have been reported, which promote us to summarize the global predicting role of CAR for survival in RCC patients. METHODS:Two reviewers independently retrieved the literature on EMBASE, MEDLINE, and Cochrane Library databases for eligible studies evaluating the associations of CAR with survival. Data related to the overall survival (OS), disease-free survival (DFS), progress-free survival (PFS), and clinicopathological features were extracted and pooled using meta-analysis with fixed or random- effect models when applicable. RESULTS:Eight studies including 2,829 patients were analyzed in the present study. High pretreatment CAR was associated with worse OS (pooled HR: 2.14, 95% CI = 1.64-2.79, p < 0.001) and DFS/PFS (pooled HR: 1.75, 95% CI: 1.31-2.35, P < 0.001). Moreover, high CAR was correlated with performance status (? 1), tumor location (left), Fuhrman grade (3-4), TNM stage (III-IV), T stage (T3-4), N stage (N1), M stage (M1), tumor necrosis (yes), venous thrombus (positive), metastasis at diagnosis (yes), NLR (> median), and PLR (> median). CONCLUSION:High pretreatment CAR is effectively predictive of worse survival in patients with RCC and could be a prognostic biomarker for those patients.
Project description:<h4>Background</h4>Anemia usually refers to low hemoglobin (Hb) levels. Previous studies indicated that anemia negatively influence the survival in various cancers. Hematocrit (HCT) is the volume percentage of red blood cells in blood, which could indicate anemia in both individuals and populations. This study compared the value of HCT with that of Hb for predicting outcomes of patients who underwent treatment for triple negative breast cancer (TNBC).<h4>Methods</h4>A retrospective study of 293 triple negative breast cancer patients, accepting treatment from January 2004 to December 2009 at Sun Yat-sen University Cancer Center, was conducted. Kaplan-Meier curves and multivariate Cox proportional models were used to calculate disease free survival (DFS) and overall survival (OS).<h4>Results</h4>The cut-off value of HCT was 35.9% determined by X-tile software analysis. The cut-off value of Hb was 12.0 g/dl based on the World Health Organization (WHO) criteria. In univariate analysis, low HCT and low Hb were both significantly associated with decreased DFS and OS. In multivariate analysis, HCT (HR: 0.570; 95% CI: 0.331-0.981, P = 0.042 for DFS; HR: 0.456; 95% CI: 0.256-0.813, P = 0.008 for OS) was still identified as independent predictor of outcome, but not Hb.<h4>Conclusion</h4>Pretreatment low HCT is independently associated with poor prognosis in TNBC patients. However, HCT was found to be superior to Hb in terms of predicting breast cancer mortality. In the future, large-scale prospective studies or validation studies are needed to verify our findings.
Project description:BACKGROUND: The value of a combined index of neutrophil and white cell counts, named derived neutrophil-lymphocyte ratio (dNLR), has recently been proposed as a prognosticator of survival in various cancer types. We investigated the prognostic role of the dNLR in a large European cohort of patients with upper tract urothelial carcinoma (UTUC). METHODS: Data from 171 non-metastatic UTUC patients, operated between 1990 and 2012 at a single tertiary academic centre, were evaluated retrospectively. Cancer-specific- (CSS) as well as overall survival (OS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of the dNLR, multivariate proportional Cox-regression models were applied. Additionally, the influence of the dNLR on the predictive accuracy of the multivariate model was further determined by Harrell's concordance index (c-index). RESULTS: The median follow-up period was 31 months. An increased dNLR was statistically significantly associated with shorter CSS (log-rank P=0.004), as well as with shorter OS (log-rank P=0.002). Multivariate analysis identified dNLR as an independent predictor for CSS (hazard ratio, HR=1.16, 95% confidence interval, CI=1.01-1.35, P=0.045), as well as for OS (HR=1.21, 95% CI=1.09-1.34, P<0.001). The estimated c-index of the multivariate model for OS was 0.68 without dNLR and 0.73 when dNLR was added. CONCLUSIONS: Patients with a high pretreatment dNLR could be predicted to show subsequently higher cancer-specific- as well as overall mortality after surgery for UTUC compared with those with a low pretreatment dNLR. Thus, this combined index should be considered as a potential prognostic biomarker in future.
Project description:Purpose:Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancer cases and is associated with a poor prognosis. In this retrospective study of patients undergoing radiation therapy as part of their treatment, disease-free survival (DFS) and overall survival (OS) of TNBC patients were examined in relation to clinical and treatment-related factors. Patients and Methods:The electronic records of 214 consecutive TNBC patients treated with surgery followed by radiotherapy at the Mid North Coast Cancer Institute between 2006 and 2016 were reviewed. Overall survival and DFS times were analyzed using the Kaplan-Meier method; multivariate Cox proportional hazard regression modelling was used to assess the significance of prognostic factors. Results:The majority of tumors were T1 (51.9%), followed by T2 (39.2%) and T3 (6.1%). For the whole group, mean DFS was 106.4 (SD 48.7) months; OS 109.4 (SD 52.1) months. Radiotherapy technique, fractionation protocol and laterality were not significant factors for DFS or OS (p>0.05). However, compared to breast conservation, mastectomy was associated with poorer DFS (mean 114.2 vs 65.2 months; p<0.0001) and poorer OS (mean 115.5 vs 80.5 months; p=0.0015). The mastectomy group had fewer patients with tumor size T1 (p=0.001) and higher proportions of T3 (p=0.001) and T4 (p=0.02). On multivariate analysis, tumor size T3/T4 and nodal status N2/N3 were significant factors for reduced DFS (p=0.023 and p=0.0003 respectively). Tumor size T3/T4 was the only significant prognostic factor for reduced OS (p=0.019). Conclusion:Advanced disease exhibited by tumor size > 5cm and positive nodal status is associated with poorer DFS in TNBC patients. Radiotherapy technique or fractionation protocol were not associated with differences in DFS or OS in our patient cohort.
Project description:The peripheral hematologic parameters of patients can be prognostic for many malignant tumors, including breast cancer, although their value has not been investigated among the different molecular subtypes of breast cancer. The purpose of this study was to examine the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte-to-monocyte ratio (LMR) in different molecular subtypes of breast cancer.A retrospective cohort of 1570 operable breast cancer patients was recruited between January 2000 and December 2010. The counts of peripheral neutrophils, lymphocytes, monocytes and platelets were collected and applied to calculate the NLR and the LMR. Univariate and multivariate Cox proportional hazard analyses were used to assess the relationship of the NLR and the LMR with disease-free survival (DFS) and overall survival (OS) in all patients and triple negative breast cancer (TNBC) patients.Univariate analysis revealed that lower NLR (?2.0) and higher LMR (>4.8) were significantly associated with superior DFS in all patients (NLR, P = 0.005; LMR, P = 0.041) and in TNBC patients (NLR, p = 0.007; LMR, P = 0.011). However, multivariate analysis revealed that only lower NLR was a significant independent predictor of superior DFS and OS in all breast cancer patients (DFS, HR = 1.50 95% CI: 1.14-1.97, P = 0.004; OS, HR = 1.63, 95% CI: 1.07-2.49, P = 0.022) and in TNBC patients (DFS, HR = 2.58, 95% CI: 1.23-5.42, P = 0.012; OS, HR = 3.05, 95% CI: 1.08-8.61, P = 0.035). Both univariate and multivariate analysis revealed that neither the NLR nor the LMR significantly predicted DFS and OS among the patients with other molecular subtypes of breast cancer.A higher pretreatment peripheral NLR significantly and independently indicated a poor prognosis for breast cancer and TNBC, and this measurement exhibited greater prognostic value than a lower LMR. The NLR was not a prognostic factor for other breast cancer subtypes.
Project description:<h4>Background</h4>Carbohydrate antigen 19-9 (CA 19-9) is one of the most frequently used tumor markers for gastrointestinal cancer, particularly for diagnostic purposes. However, its value in predicting prognosis remains controversial. In this study, we sought to clarify this by conducting a meta-analysis of relevant studies.<h4>Methods</h4>We systematically searched several databases, including PubMed, EMBASE and Web of Science for articles pertaining to the relationship between pretreatment serum CA 19-9 levels and prognosis in patients with colorectal cancer (CRC). The reported hazard ratios (HR) of overall survival (OS), disease-free survival (DFS), pooled progression-free survival (PFS) and recurrence-free survival (RFS) in the analyzed studies were compared by fixed effects/random effects models.<h4>Results</h4>Seventeen studies involving 6434 patients with CRC were included in our meta-analysis. A comprehensive analysis of the collected data revealed that high serum CA 19-9 levels before treatment were significantly associated with poor OS (HR: 1.58, 95% CI: 1.36-1.83, P<0.001), DFS (HR: 1.71, 95% CI: 1.38-2.13, P<0.001), PFS (HR: 1.30,95%CI:0.93-1.82, P = 0.121) and RFS (HR: 1.43, 95% CI: 1.11-1.83, P = 0.006). This association between high pretreatment serum CA 19-9 levels and poor survival held true across different geographical regions, analysis types, methods used for HR determination, sample size, and treatment methods.<h4>Conclusions</h4>The results of this study indicate that pretreatment serum CA 19-9 level can be used as a prognostic indicator for patients with CRC.
Project description:BACKGROUND:Previous studies have shown that branched-chain amino acid transferase 1 (BCAT1) is associated with tumour progression in triple-negative breast cancer (TNBC). Furthermore, CD133 has emerged as a novel cancer stem cell marker for indicating tumour progression. However, the prognostic significance of these two markers remains to be verified. This study was conducted to investigate the correlation between BCAT1 and CD133 expression and clinicopathological features, as well as the prognosis of patients with TNBC. METHODS:The study cohort included 291 patients with TNBC. Tissue microarrays were constructed for both cancer and normal tissues. The expression of BCAT1 and CD133 was detected by immunohistochemical staining, and the levels were evaluated using an H-scoring system. Cut-off points for BCAT1 and CD133 expression were determined using receiver operating characteristic curves. RESULTS:The median follow-up time for the study participants was 68.73?months (range: 1.37-103.6?months). The 5-year disease-free survival (DFS) and overall survival (OS) rates of the 291 patients with TNBC were 72.51 and 82.47%, respectively. Higher levels of BCAT1 and CD133 expression independently indicated shorter DFS and OS. High levels of both BCAT1 and CD133 expression were detected in 36 (12.37%) patients, who had significantly shorter DFS and OS (both P?<?0.001) compared to other patients. CONCLUSION:BCAT1 and CD133 can be considered as biomarkers with prognostic significance for TNBC.
Project description:Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear.This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0-29.9), slightly obese (BMI 30.0-34.9), moderately obese (BMI 35.0-39.9) and severely obese (BMI ≥ 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors.Multivariate analyses revealed an independent prognostic effect of BMI on DFS (p = 0.001) and OS (p = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71-4.28, p < 0.001) and OS (HR 2.79, 95 % CI 1.63-4.77, p < 0.001), while moderately obese, slightly obese and overweight patients did not differ from underweight/normal weight patients with regard to DFS or OS. Subgroup analyses showed a similar significant effect of BMI on DFS and OS in patients with triple-negative breast cancer (TNBC), but not in patients with other tumor subtypes.Severe obesity (BMI ≥ 40) significantly worsens prognosis in early breast cancer patients, particularly for triple-negative tumors.Clinicaltrials.gov NCT02181101 . Registered September 2005.
Project description:As a cell proliferation biomarker, Ki-67 is principally used in ER+/HER2- breast cancer. However, the importance and the best cutoff point of Ki-67 in triple-negative breast cancer (TNBC) remains unclear and was evaluated in this study.A total of 1800 patients with early invasive TNBC between 2011 and 2016 at Fudan University Shanghai Cancer Center were consecutively recruited for this study. The optimal cutoff for Ki-67 was assessed by Cutoff Finder. Propensity score matching (PSM, ratio?=?1:2) was performed to match the Ki-67low group with the Ki-67high group. Overall survival (OS) and disease-free survival (DFS) were compared between the two groups using the Kaplan-Meier method and Cox regression model. The most relevant cutoff value for Ki-67 for prognosis was 30% (p?=?0.008). At the cutoff point of 30%, worse DFS and OS were observed in the Ki-67high group. In multivariate analyses, N-stage (p?<?0.001), T-stage (p?=?0.038), and Ki-67 at the 30% threshold (p?=?0.020) were independently linked to OS. In subgroup analysis, Ki-67 cutoff at 30% had prognostic and predictive potential for DFS with either tumor size ?2?cm (p?=?0.008) or lymph node-negative (N-) (p?=?0.038) and especially with T1N0M0 (stage I) TNBCs. For 945 N- TNBC patients, adjuvant chemotherapy (CT) was associated with better OS in the Ki-67high group (p?=?0.017) than in the Ki-67low group (p?=?0.875). For stage I/Ki-67low patients, adjuvant CT did not affect DFS (p?=?0.248). Thus, Ki-67 cutoff at 30% had early independent prognostic and predictive potential for OS and DFS in TNBCs, and Ki-67?>?30% was significantly associated with worse prognosis, especially for stage I patients. For stage I/Ki-67low TNBC patients, the advantage of CT is unclear, providing the basis for future de-escalation therapy.