Additional capecitabine use in early-stage triple negative breast cancer patients receiving standard chemotherapy: a new era? A meta-analysis of randomized controlled trials.

BACKGROUND: The efficiency of capecitabine has been proven in early-stage triple negative breast cancer (eTNBC) with residue invasive tumor (non-pCR) after standard neoadjuvant chemotherapy (NACT). However, for those unselected eTNBC patients without screening from NACT (i.e., newly diagnosed eTNBC patients undergoing breast surgery followed by adjuvant systemic therapy), the value of capecitabine has still remains unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate whether additional capecitabine in eTNBC patients could improve clinical outcomes. METHODS: Seven RCTs (USO 01062, FinXX, GEICAM/2003, CREATE-X, CIBOMA/2004, CBCSG-010 and SYSUCC-001) were identified in online databases until December 2020 and included in the meta-analysis. We extracted the survival data including disease/relapse-free survival (DFS/RFS) and overall survival (OS), and utilized the STATA software to calculate the summarized hazard ratios (HRs) and 95% confidence intervals (95%CIs). RESULTS: A total of 3329 eTNBC patients were enrolled in this meta-analysis, with 1640 receiving standard neo-/adjuvant chemo-regimes alone, and the other 1689 receiving an additional capecitabine use, respectively. Both DFS and OS were significantly improved with the addition of capecitabine, and the benefits remained consistent in those unselected eTNBC patients without screening from NACT. Subgroup analysis further proved that this improvement in DFS was significant in both nodal negative and positive patients. Similar benefits are also found across menopausal status (both pre- and post-menopause). Regarding toxicity, the hand-foot syndrome and neutropenia are the most common capecitabine related adverse events, and are mostly tolerable. CONCLUSIONS: The present meta-analysis of RCTs demonstrates for the first time that adding capecitabine to standard chemo-regimens could improve both DFS and OS in unselected eTNBC patients, and this benefit remains consistent regardless of nodal status and menopausal status, which may lead eTNBC therapy into a new era.

WWC2 is an independent prognostic factor and prevents invasion via Hippo signalling in hepatocellular carcinoma.

WWC family proteins negatively regulate HEK293 cell proliferation and organ growth by suppressing the transcriptional activity of Yes-associated protein (YAP), a major effector of the Hippo pathway. The function of the scaffolding protein WWC1 (also called KIBRA) has been intensively studied in cells and animal models. However, the expression and clinicopathologic significance of WWC2 in cancer are poorly characterized. This study aimed to clarify the biological function and mechanism of action of WWC2 in hepatocellular carcinoma (HCC). Retrospective analysis revealed WWC2 was significantly down-regulated in 95 clinical HCC tissues compared to the paired adjacent non-cancerous tissues. Moreover, loss of WWC2 expression was significantly associated with advanced clinicopathological features, including venous infiltration, larger tumour size and advanced TNM stage. Positive WWC2 expression was associated with significantly better 5-year overall survival, and WWC2 was an independent prognostic factor for overall survival in HCC. Moreover, we confirmed WWC2 inhibits HCC cell invasive ability in vitro. Elevated YAP expression was also observed in the same cohort of HCC tissues. Pearson's correlation coefficient analysis indicated WWC2 expression correlated inversely with nuclear YAP protein expression in HCC. Mechanistically, we confirmed overexpression of WWC2 suppresses the invasive and metastatic potential of HCC cells by activating large tumour suppressor 1 and 2 kinases (LATS1/2), which in turn phosphorylates the transcriptional co-activator YAP. Overall, this study indicates WWC2 functions as a tumour suppressor by negatively regulating the Hippo signalling pathway and may serve as a prognostic marker in HCC.

The tumor-to-breast volume ratio (TBR) predicts cancer-specific survival in breast cancer patients who underwent modified radical mastectomy.

Breast cancer is the most common cancer in women globally, and tumor size measured as the largest diameter of the tumor focus is currently used in tumor-lymph node-metastasis (TNM) staging for prognosis and treatment decisions. The present study utilized the tumor-to-breast volume ratio (TBR) to evaluate the relative tumor size and determined the prognostic impact of TBR on survival in patients with breast cancer. Two thousand twenty-five consecutive breast cancer patients who underwent modified radical mastectomy between January 2002 and December 2008 at Sun Yat-Sen University Cancer Center were enrolled in this retrospective study. Kaplan-Meier analysis was used to assess the prognostic effect of TBR on cancer-specific survival (CSS), and univariate log-rank test and multivariate Cox proportional hazards regression model were performed to identify independent prognostic factors. The optimal cutoff value of TBR was determined to be 1.70 %, and 1473 and 552 patients were categorized to low-TBR and high-TBR groups, respectively. In the whole patient cohort, CSS was significantly shorter in the high-TBR group (110.2 vs 128.5 months, P < 0.001). Univariate and multivariate analyses revealed that TBR was an independent prognostic factor of CSS in breast cancer patients (hazard ratio (HR) 1.489, 95 % CI 1.130-1.961, P = 0.005). High TBR was independently associated with poor prognosis in breast cancer patients. This variable may serve as a valuable parameter to predict the outcomes of breast cancer.

New classification for advanced breast cancer patients experiencing disease progression during salvage treatment: a single-center retrospective cohort study.

Background: Attributed to inter-tumor heterogeneity, the therapeutic effect of salvage treatment is diverse and different malignant lesions might manifest various therapeutic responses among advanced breast cancer (ABC) patients. The present study aimed to explore the influence of the mode of lesion response on the subsequent treatment and to subclassify ABC patients for precise prognosis prediction. Methods: Based on the inclusion and exclusion criteria, ABC patients were retrospectively collected and followed up in the Guangdong Provincial Hospital of Chinese Medicine between 2018 and 2021. The treatment responses of all malignant lesions were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Testing subclassified models were constructed based on different assembly mode of progressed malignant lesions for further classification of ABC patients experiencing disease progression following first-line treatment. Multivariate survival analyses were performed to assess the second-line progression-free survival (PFS) of various subgroups and screen the suitable classification model. The most suitable model was utilized to classify enrolled ABC patients as a heterogeneous progression-disease (Heter-PD) group or homogeneous progression-disease (Hom-PD) group. Univariate analysis and multivariate Cox regression survival analyses were performed to assess the prognostic value of each variable. Results: A total of 70 ABC patients experiencing disease progression after first-line treatment were enrolled into the analyses and underwent median follow-up of 10.36 months. We constructed 3 testing models and Model C (Hom-PD was defined when all the target and non-target lesions were evaluated as progression, with or without new lesions) could further distinguish ABC patients with worse survival. The second-line progression-free survival (PFS) times were significantly different between two groups (11.04 vs. 6.07 months, P=0.034). For ABC patients retaining partial medication after disease progression of first-line treatment, the Heter-PD group showed a tendency of better second-line PFS than the Hom-PD group (13.18 vs. 3.61 months, P=0.430). Conclusions: Based on the disease progression mode after first-line treatment, the classification model could classify ABC patients as Hom-PD and Heter-PD subgroups, which manifest distinct prognoses during the sequential treatment. For Heter-PD patients, retainment of partial medication might be a rational choice for second-line therapy.

Incidence and management of pyrotinib-associated diarrhea in HER2-positive advanced breast cancer patients.

BACKGROUND: The PHOEBE study showed that pyrotinib is an alternative treatment option for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer after trastuzumab and chemotherapy. Diarrhea was a common adverse event that could compromise or modify treatment administration. METHODS: We conducted a retrospective cohort study of HER2-positive advanced breast cancer patients receiving a pyrotinib-based regimen between August 2018 and January 2021. The risk of diarrhea with 95% confidence limits (CLs) was calculated and management was analyzed. RESULTS: A total of 46 HER2-positive advanced breast cancer patients were enrolled. Diarrhea of any grade occurred in 100% of patients, and grade 3 diarrhea was observed in 52.2% (n=24) of patients. Treatment dose modification was implemented in 39.1% (n=18) of advanced breast cancer patients. Compared with other treatment regimens, patients receiving pyrotinib plus vinorelbine suffered the highest risk of diarrhea (60%), though no significant difference was confirmed (P=0.77). Antidiarrheal agents were commonly used and loperamide-based regimens achieved an ideal antidiarrheal effect (95.3-100%), while non-loperamide-based regimens (such as montmorillonite powder) had a lower control rate (78.6%). CONCLUSIONS: Diarrhea was a common adverse event of pyrotinib-based treatment, and approximately 50% of patients suffered high grade diarrhea. Loperamide-based antidiarrheal agents could commendably manage most episodes.

The Influence of Hormone Therapy on secondary diabetes mellitus in Breast Cancer: A Meta-analysis.

BACKGROUND: Growing evidences have implied that patients with primary breast cancer (BC) were at increased risks of developing diabetes mellitus (DM). However, as a major adjuvant treatment, the influence of hormone therapy (HT) on secondary DM in primary BC remains controversial; we conducted a meta-analysis of existing studies to evaluate the association of hormone therapy and secondary DM. METHODS: We searched online databases (PubMed, EMBASE, the Cochrane library, Scopus, and Google Scholar) for studies exploring the influence of hormone therapy on secondary DM in BC. The summarized effect sizes (ES) and 95% confidence interval (95% CI) are calculated by STATA software utilizing fixed-effect or random-effect models, depending on the heterogeneity of the eligible studies. RESULTS: Ultimately, 7 retrospective publications including a total of 44,524 primary BC patients are eligible in present meta-analysis. HT use significantly increased the risk of developing DM in primary BC patients, whenever compared with NON-HT BC patients (pooled adjusted HR 1.30, 95% CI: 1.19-1.43) or NORMAL participants (HR 1.19, 95% CI: 1.14-1.25). As to specific HT medications, our sub-analysis demonstrates the risk for DM in tamoxifen (TAM) users elevates by 30% than NON-TAM use BC patients (pooled HR 1.30, 95% CI: 1.20-1.40) and by 18% than NORMAL participants (pooled HR 1.18, 95% CI: 1.12-1.24). However, for aromatase inhibitors (AIs) users, the risks for DM do not elevate significantly. Funnel plots and Egger's tests are used to evaluate publication bias and no apparent bias is detected in all analysis. CONCLUSION: The present study is the first meta-analysis which thoroughly reveals that adjuvant HT is a risk factor of secondary DM in primary female BC patients. As to specific HT medications, TAM use significantly enhances the incidence of secondary DM, while AIs use does not influence the DM incidence significantly. Our results can help clinicians to tailor more appropriate strategies for the therapy and follow-up of primary BC patients.

Survival benefit of platinum-based regimen in early stage triple negative breast cancer: A meta-analysis of randomized controlled trials.

Platinum (Pt)-based chemo-regimens have been proved effective in neoadjuvant and salvage chemotherapy of triple negative breast cancer (TNBC). However, the survival benefit of Pt-based regimens in early stage TNBC(eTNBC) treatment has remained unclear. We conducted a meta-analysis to explore its role in improving the clinical outcomes of eTNBC. We carried out a comprehensive literature search on 15 March 2021 for randomized controlled trials (RCTs) comparing ajuvant/neoadjuvant Pt-based and Pt-free chemo-regimens in eTNBC patients, according to PRISMA 2020. We extracted the survival data and utilized the STATA software to calculate the summarized hazard ratios (HRs) and 95% confidence interval (95% CI) for overall survival (OS) and disease-free survival (DFS). Seven eligible RCTs enrolling a total of 2,027 eTNBC patients were identified in this meta-analysis, with 1,007 receiving Pt-free regimens, and the other 1,020 patients receiving Pt-based regimens, respectively. Patients in Pt-based regimens arm were associated with significant improved DFS (HR = 0.70, 95% CI: 0.58-0.84), and OS (HR = 0.78, 95% CI: 0.61-1.00). The survival benefits of DFS remained consistent in both the two strategies of Pt usage, either adding Pt to standard anthracyclines&taxanes based regimens (A&T + Pt), or combination of Pt and taxanes alone (TPt). The survival benefits also remained consistent in either neoadjuvant or adjuvant use of Pt. The present meta-analysis of RCTs revealed that Pt-based chemo-regimens could significantly improve both DFS and OS for eTNBC patients. Based on efficiency and toxicity, we recommend Pt-based regimens for eTNBC, especially the "A&T + Pt" mode if the toxicities are tolerable, which may lead TNBC therapy into a new era.

Network Pharmacology-Based Identification of Key Mechanisms of Xihuang Pill in the Treatment of Triple-Negative Breast Cancer Stem Cells.

Xihuang pill, an approved Chinese medicine formula (state medical permit number. Z11020073), is a commonly used adjuvant drug for cancer patients in China. Xihuang pill has a satisfactory effect in treating breast cancer in clinics, especially triple-negative breast cancer (TNBC), which is the most aggressive type of breast cancer, and finite effective therapies. However, the mechanism of Xihuang pill in treating TNBC remains unclear. The present study aims to explore the pharmacological mechanism of Xihuang pill in treating advanced TNBC. We identified the main chemical components of Xihuang pill by using HPLC-Q-TOF-MS/MS. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis shows that serum containing Xihuang pill (XS) had no obvious killing effect on any subtype of breast cancer cells, but it inhibited mammosphere colony formation of two TNBC cell lines (4T1 and HCC1806 cells) and could enhance the inhibitory effect of paclitaxel (PTX) on the proliferation of 4T1 and HCC1806 cells when combined with PTX. Seventy-six active compounds in Xihuang pill, their 300 protein targets, and 16667 TNBC stem cell-related genes were identified. The drug-herb-active compound-target gene-disease network and enrichment analyses were constructed with 190 overlapping candidate targets. Through text mining and molecular docking, the target gene NR3C2 and its active compound naringenin were selected for further validation. According to the TCGA database, we observed that a high expression of NR3C2 promoted a higher survival probability regarding overall survival (OS). In vitro experiments indicated that naringenin presented an identical effect to XS, possibly by regulating the NR3C2 expression. Overall, this study explored the effect of Xihuang pill in treating advanced TNBC cells and showed that naringenin, which is the key active compound of Xihuang pill, could lessen the stemness of TNBC cells to produce a synergistic effect on PTX by regulating the NR3C2 gene.

The role of surgical intervention for isolated breast cancer liver metastasis: Results of case-control study with comparison to medical treatment.

BACKGROUND: Combined with systemic therapy, the surgical intervention for breast cancer liver metastases (BCLM) is increasingly accepted but lacks convincing evidence. The aim of this study was to evaluate the disease control efficacy of hepatic surgery in isolated BCLM patients. METHODS: Between 2012 and 2017, metastatic breast cancer patients with isolated liver metastasis and regular follow-up were identified. Cohort design was conducted to compare the progression-free survival (PFS) between the surgical and nonsurgical BCLM patients. Univariate analysis and multivariate Cox regression survival analyses were performed to identify significant prognostic factors. RESULT: In all, 148 isolated BCLM patients were enrolled and 95 participants received hepatic surgery for metastatic lesions. With median follow-up of 36.47 months, there was no significant difference between hepatic surgical group and nonsurgical group for PFS (median PFS: 11.17 months vs 10.10 m, P = .092). Based on the multivariate analysis, the disease-free interval (DFI) was an independent prognostic factor for isolated BCLM patients. Among the surgical group, BCLM patients who had ideal response after first salvage systemic treatment experienced the best long-term survival (median PFS: 14.20 months). CONCLUSION: For isolated BCLM patients with ideal response in first-line medical treatment, surgical intervention (hepatectomy, radiofrequency ablation) combining with systemic treatment could bring improved progression-free survival compared to sole systemic treatment, indicating that hepatic surgery may be considered as a therapeutic choice for selected isolated BCLM patients in clinical practice.

Synergistic Effect Between Full-Term Pregnancy/Breastfeeding And Familial Susceptibility On Breast Cancer Risk.

BACKGROUND: Breast cancer is the most common cancer in women worldwide, and reproductive factors and family history of malignancy are considered as high risk factors. The present study aimed to evaluate the synergistic effect of reproductive factors and family history on breast cancer. METHOD: A total of 1215 breast cancer patients and 1215 control participants from two medical centers were enrolled, and reproductive factor history and family cancer history information was collected. Multivariate logistic regression analyses were performed to estimate the adjusted odds ratio (OR), and synergy index (SI) was used to assess the combined effect of potential factors. RESULTS: Compared to the controls, a negative association between full-term pregnancy/breastfeeding and breast cancer was observed regardless of the status of family cancer history (OR: 0.675, 95% CI: 0.560-0.814 and OR: 0.631, 95% CI: 0.503-0.789 respectively) after adjustment of other confounders, while the risk effect of abortion was unproven. The synergistic effect of history of full-term pregnancy and family history of malignancy was indicated in the combined analyses with SI as 9.429 (95% CI:1.248-71.245). CONCLUSION: Full-term pregnancy/breastfeeding were protective factors against breast cancer and synergistic additive effect was demonstrated between no full-term pregnancy/breastfeeding and a family history of malignancy on the risk of breast cancer.

SATB2 is a Promising Biomarker for Identifying a Colorectal Origin for Liver Metastatic Adenocarcinomas.

SATB2 (Special AT-rich sequence-binding protein 2) has recently been shown to be a specific biomarker of colorectal cancer (CRC). The aim of this study was to investigate the diagnostic potential of SATB2 as a means of detecting a CRC origin for liver metastases. SATB2 expression was examined in a resection cohort of 101 CRC and 273 non-CRC adenocarcinoma samples using immunohistochemistry (IHC). The diagnostic accuracy of CRC origins of liver metastases based on SATB2 and a three marker panel of SATB2, CK20 and CDX2 was evaluated using an independent cohort of 192 liver biopsies. IHC showed 97 of the 101 (96.0%) primary CRC samples were SATB2 positive, compared to only 6 of the 273 (2.1%) samples of other cancer types. The sensitivity, specificity and AUC values of SATB2 expression in resection samples were 97%, 97.1% and 0.977, respectively. Meanwhile, for the liver biopsy samples, the sensitivity, specificity and AUC values of a CRC liver metastases was 92.2%, 97.8% and 0.948 for SATB2, 95.1%, 91.0% and 0.959 for CK20, and 100%, 85.4% and 0.976 for CDX2, respectively. Further analysis demonstrated that all three-marker positivity was detected in 92/103 (89.3%) CRC and 2/89 (2.2%) non-CRC liver metastases sampled by biopsy. Our findings suggest that SATB2, as measured by IHC, could serve as a promising diagnostic biomarker of CRC metastases. Combining evaluation of SATB2 with CK20 and CDX2 to form a three marker panel further improved the detection of metastatic CRCs in liver biopsy tissues.

Development and validation of a nomogram for predicting survival on the base of modified lymph node ratio in breast cancer patients.

BACKGROUND: Axillary lymph node status is one of the most important prognostic factors in breast cancer and previous studies indicated that lymph node ratio (LNR) could better predict the outcome than the counting of positive lymph nodes. In the current study, we evaluated the prognostic effect of modified LNR in breast cancer patients. METHODS: A total of 3339 breast cancer patients undergoing axillary lymph nodes dissection were enrolled and respectively analyzed. Seventy five percent of participants were randomly selected as training cohort and the remaining 25% were as validation cohort. Univariate and multivariate analyses were performed and the prognostic impact of mLNR was compared with pN staging. A prognostic nomogram was established and externally validated in the validation cohort. RESULT: In multivariate analysis, both the mLNR and pN staging were independent prognostic factors for breast cancer patients, and the mLNR manifested superior discrimination power than the pN stages regardless of the total number of lymph nodes retrieved and the lymph node status. The nomogram was built including the identified independent prognostic factors and the calibration curves indicated optimal agreement between nomogram prediction and actual observation. The Concordance index (C-index) of the nomogram was statistically higher than that of the TNM system (0.747 vs. 0.711 in training cohort, 0.789 vs. 0.760 in validation cohort, both p < 0.05). CONCLUSION: Modified LNR is an important prognostic parameter and can predict survival more accurately than pN staging. The novel nomogram could provide individual prediction for breast cancer patients and help clinicians in treatment option making and prognosis evaluation.

High Residual Tumor Rate for Early Breast Cancer Patients Receiving Vacuum-assisted Breast Biopsy.

Purpose: The objective of study is aiming to investigate the residual tumor rate after Vacuum-assisted Breast Biopsy (VABB) for early breast cancer excision and the efficacy of mammogram and ultrasound in detecting residual tumor. Methods: Patients who underwent VABB and were confirmed with breast cancer in Sun Yat-sen University Cancer Center from 2010 to 2015 were reviewed retrospectively. The residual tumor rate determined by histological examination was calculated, and then was compared with the results estimated by mammogram and ultrasound which were performed post VABB but before subsequent surgery. Univariate and multivariate analysis (logistic regression) were carried out to identify the independent risk factors associated with residual tumor. Results: In total, 126 eligible patients with early breast cancer were recruited for this study, of whom 79 (62.7%) had residual tumor and 47 (37.3 %) underwent complete excision. The residual tumor rates for lesions < 10mm, lesions 10 to 20 mm and lesions >20mm in size were 55.0%, 68.9% and 53.1%, respectively. The complete excision rates estimated by mammogram and ultrasound were 76.5% and 73.9%, with a negative predictive value of only 46.2% and 50.6%, respectively. In the multivariate logistic regression analysis, no specific factors were found associated with risk of residual tumor (all P > 0.05). Conclusions: There was a high residual tumor rate after VABB in early breast cancer. Both mammogram and ultrasound could not effectively detect the residual tumor after VABB.

Development and validation of a prognostic nomogram based on the log odds of positive lymph nodes (LODDS) for breast cancer.

BACKGROUND: To evaluate the prognostic effect of log odds of positive lymph nodes (LODDS) and develop a nomogram for survival prediction in breast cancer patients at the time of surgery. RESULTS: LODDS was an independent risk factor for cancer-related death in breast cancer (hazard ratio: 1.582, 95%CI: 1.190-2.104). Menopausal status, tumor size, pathological lymph node staging, estrogen receptor status and human epidermal growth factor receptor-2 status were also included in the nomogram. The calibration plots indicated optimal agreement between the nomogram prediction and actual observation. Discrimination of nomogram was superior to the seventh edition TNM staging system [C-index: 0.745 vs. 0.721 (p = 0.03) in training cohort; 0.796 vs. 0.726 (p < 0.01) in validation cohort]. METHODS: We retrospectively evaluated 2023 breast cancer patients from Jan 2002 to Dec 2008 at our center. The cohort was randomly divided into training cohort and validation cohort. Univariate and multivariate analyses were performed to identify prognostic factors, and nomogram was established using Cox regression model in training cohort. External validation of the nomogram was performed in the validation cohort. CONCLUSIONS: The LODDS is an independent prognostic indicator in breast cancer and the novel nomogram can provide individual prediction of cancer-specific survival and help prognostic assessment for breast cancer patients.

The miR-34a-LDHA axis regulates glucose metabolism and tumor growth in breast cancer.

Lactate dehydrogenase A (LDHA) is involved in a variety of cancers. The purpose of this study was to investigate the expression, prognostic roles and function of LDHA in breast cancer. We found that LDHA was upregulated in both breast cancer cell lines and clinical specimens using quantitative real-time PCR (qRT-PCR). Immunohistochemistry (IHC) analysis of tissue microarrays (TMAs) showed that high LDHA expression was associated with cell proliferation, metastasis and poor patient overall survival (OS) and disease free survival (DFS). Furthermore, we found that LDHA promoted glycolysis and cell proliferation in vitro and in vivo. We also performed luciferase reporter assays and found that LDHA was a direct target of miR-34a. Repression of LDHA by miR-34a suppressed glycolysis and cell proliferation in breast cancer cells in vitro. Our findings provide clues regarding the role of miR-34a as a tumor suppressor in breast cancer through the inhibition of LDHA both in vitro and in vivo. Targeting LDHA through miR-34a could be a potential therapeutic strategy in breast cancer.

The Practicability of a Novel Prognostic Index (PI) Model and Comparison with Nottingham Prognostic Index (NPI) in Stage I-III Breast Cancer Patients Undergoing Surgical Treatment.

BACKGROUND: Previous studies have indicated the prognostic value of various laboratory parameters in cancer patients. This study was to establish a prognostic index (PI) model for breast cancer patients based on the potential prognostic factors. METHODS: A retrospective study of 1661 breast cancer patients who underwent surgical treatment between January 2002 and December 2008 at Sun Yat-sen University Cancer Center was conducted. Multivariate analysis (Cox regression model) was performed to determine the independent prognostic factors and a prognostic index (PI) model was devised based on these factors. Survival analyses were used to estimate the prognostic value of PI, and the discriminatory ability of PI was compared with Nottingham Prognostic Index (NPI) by evaluating the area under the receiver operating characteristics curves (AUC). RESULTS: The mean survival time of all participants was 123.6 months. The preoperative globulin >30.0g/L, triglyceride >1.10mmol/L and fibrinogen >2.83g/L were identified as risk factors for shorter cancer-specific survival. The novel prognostic index model was established and enrolled patients were classified as low- (1168 patients, 70.3%), moderate- (410 patients, 24.7%) and high-risk groups (83 patients, 5.0%), respectively. Compared with the low-risk group, higher risks of poor clinical outcome were indicated in the moderate-risk group [Hazard ratio (HR): 1.513, 95% confidence interval (CI): 1.169-1.959, p = 0.002] and high-risk group (HR: 2.481, 95%CI: 1.653-3.724, p< 0.001). CONCLUSIONS: The prognostic index based on three laboratory parameters was a novel and practicable prognostic tool. It may serve as complement to help predict postoperative survival in breast cancer patients.

Prognostic Significance of Preoperative Circulating Monocyte Count in Patients With Breast Cancer: Based on a Large Cohort Study.

Growing evidence showed that inflammation response plays an important role in cancer development and progression, and absolute lymphocyte count (ALC), absolute monocyte count (AMC), and lymphocyte to monocyte ratio (LMR) have been used as parameters of systemic inflammation in several tumors. In this study, we evaluated the prognostic significance of preoperative ALC, AMC and LMR in breast cancer and 2000 patients between January 2002 and December 2008 at Sun Yat-Sen University Cancer Center were enrolled. Patients were grouped by the cut-off value according to the receiver operating characteristics (ROC) curve analysis. Kaplan-Meier analysis showed that patients with elevated AMC levels (>0.48 × 10/L) had shorter overall survival (OS, P < 0.001). In multivariate analysis, preoperative AMC was identified as an independent prognostic parameter for OS in breast cancer patients (hazard ratio = 1.374, 95% confidence interval: 1.045-1.807). Subgroup analyses revealed that AMC was an unfavorable prognostic factor in stage II-III breast cancer patients and Luminal B, human epithelial growth factor receptor-2 overexpressing subtype, and triple-negative breast cancer (all P < 0.05). Additionally, the prognostic value of ALC and LMR could not be proven in the current study. Preoperative AMC may serve as an easily available and low-priced parameter to predict the outcomes of breast cancer.

The preoperative plasma fibrinogen level is an independent prognostic factor for overall survival of breast cancer patients who underwent surgical treatment.

BACKGROUND: Previous studies have suggested that plasma fibrinogen contributes to tumor cell proliferation, progression and metastasis. The current study was performed to evaluate the prognostic relevance of preoperative plasma fibrinogen in breast cancer patients. METHOD: Data of 2073 consecutive breast cancer patients, who underwent surgery between January 2002 and December 2008 at the Sun Yat-sen University Cancer Center, were retrospectively evaluated. Plasma fibrinogen levels were routinely measured before surgeries. Participants were grouped by the cutoff value estimated by the receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed using Kaplan-Meier analysis, and multivariate Cox proportional hazards regression model was performed to evaluate the independent prognostic value of plasma fibrinogen level. RESULTS: The optimal cutoff value of preoperative plasma fibrinogen was determined to be 2.83 g/L. The Kaplan-Meier analysis showed that patients with high fibrinogen levels had shorter OS than patients with low fibrinogen levels (p < 0.001). Multivariate analysis suggested preoperative plasma fibrinogen as an independent prognostic factor for OS in breast cancer patients (HR = 1.475, 95% confidence interval (CI): 1.177-1.848, p = 0.001). Subgroup analyses revealed that plasma fibrinogen level was an unfavorable prognostic parameter in stage II-III, Luminal subtypes and triple-negative breast cancer patients. CONCLUSION: Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients.