Jia-Yuan Sun

Prognostic Value of Metastatic Axillary Lymph Node Ratio for Chinese Breast Cancer Patients

Objective The prevalence of breast cancer varies among countries and regions. This retrospective study investigated the prognostic value of the lymph node ratio (LNR) compared with the number of positive lymph nodes (pN) in Chinese breast cancer patients. Methods The medical records of female breast cancer patients (N = 2591) were retrospectively evaluated. The association of LNR and TMN staging system were compared with respect to overall, disease-free, and distant metastasis-free survival. Results Out of 2591 patients, 2495 underwent modified radical surgery and 96 received breast conserving surgery. All patients had adjuvant chemotherapy following surgery. The median follow up period 66.9 months (range 5–168 months). The 5-year and 10-year overall survival rates were 89.3% and 78.8%, respectively, and 5-year disease-free survival and distant metastasis-free survival rates were 81.6% and 83.5%, respectively. Univariate analysis indicated that in general T, pN, LNR, as well as tumor expression of the estrogen receptor, progesterone receptor, and HER2 were associated with overall, disease-free, and distant metastasis-free survival (all P-values <0.05). Mutlivariate analysis found pN stage and LNR were independent predictors of overall, disease-free, and distant metastasis-free survival (all P-values <0.001). If pN stage and LNR were both included in a multivariate analysis, LNR was still an independent prognostic factor for overall, disease-free, and distant metastasis-free survival (all P-values <0.001). Conclusion Our findings support the use of LNR as a predictor of survival in Chinese patients with breast cancer, and that LNR is superior to pN stage in determining disease prognosis.

Prognostic Value of Ki-67 in Breast Cancer Patients with Positive Axillary Lymph Nodes: A Retrospective Cohort Study

Introduction Ki-67 expression is a biomarker for proliferation. Its prognostic value is recognized in breast cancer (BC) patients with negative axillary nodes, but is less clear in BC patients with positive axillary lymph nodes. Methods We retrospectively reviewed the medical records of 1131 Chinese BC patients treated from January 2002 to June 2007 and 450 patients met the inclusion criteria: positive nodes, adjuvant therapy, and complete biomarker profile (estrogen receptor (ER), progesterone receptor (PR), HER2, p53, Ki-67). Univariate and multivariate regression analysis were used to correlate biomarkers and tumor characteristics with metastasis free survival (MFS) and overall survival (OS). Results Median follow-up time was 46 months (range 5–76 months). The Ki-67 expression was associated significantly with histological grade, ER, PR, HER2, and P53 status (P<0.05). Tumor stage, nodal stage, and ER status were independent prognostic factors for MFS. Ki-67 status was associated significantly with OS but not MFS. To determine whether the extent of LN involvement in the BC patients influenced the role of Ki-67 in survival rates, we compared these variables in patients with 1–3 positive lymph nodes (N1) to those of patients with ≥4 positive lymph nodes. Ki-67 status was an independent prognostic factor for MFS (Hazard Ratio, 3.27, P = 0.026) and overall survival (HR, 10.64, P = 0.007) in patients with 1–3 positive nodes (N1). Conclusions The possibility that Ki-67 expression together with clinical factors can improve prediction of the prognosis of BC patients with 1∼3 positive axillary lymph nodes warrants further studies.

Correction: Postmastectomy Radiotherapy Improves Disease-Free Survival of High Risk of Locoregional Recurrence Breast Cancer Patients with T1-2 and 1 to 3 Positive Nodes

Objectives The indications for post-mastectomy radiotherapy (PMRT) with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node. Methods We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients). Results The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS) (P = 0.010). Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005), but did not affect distant metastasis-free survival (DMFS) (P = 0.494), disease-free survival (DFS) (P = 0.215), and overall survival (OS) (P = 0.645). For patients without PMRT, the 5-year LRFS of low-risk patients (0–1 risk factor for locoregional recurrence) of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence) (80.9%, P < 0.001). PMRT improved LRFS (P = 0.001) and DFS (P = 0.027) in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients. Conclusions PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

Downregulation of hsa_circ_0011946 suppresses the migration and invasion of the breast cancer cell line MCF-7 by targeting RFC3

Introduction Although some circRNAs have been found to regulate the progression of malignancies, their functions and coupled molecular mechanisms are still unclear. In our study, we sought to assess the underlying molecular mechanisms of circRNAs in breast cancer and therefore explored the differentially expressed circRNAs and co-expression networks, followed by in vitro experiments. Materials and methods High-throughput RNA sequencing was performed to obtain an unbiased profile of circRNA expression. CircRNA-miRNA-mRNA co-expression networks were predicted, and sequence analyses were carried out. The MTT, transwell migration and invasion assay was conducted in Michigan Cancer Foundation-7 cells that had been transfected with si-circRNA and si-negative control (si-NC). Results A total of 152 circRNAs were differentially expressed in breast cancer tissues, among which 85 were upregulated and 67 downregulated. Out of these, hsa_circ_0011946 was selected and the subsequent bioinformatics analysis predicted that hsa_circ_0011946 sponging miR-26a/b directly targeted replication factor C subunit 3 (RFC3) and that its knockdown could inhibit RFC3 mRNA and protein expression. Furthermore, hsa_circ_0011946 loss-of-function significantly suppressed the migration and invasion of Michigan Cancer Foundation-7 cells. Conclusion Together, these results indicate that hsa_circ_0011946 and RFC3 comprise a novel pathway involved in the progression of breast cancer.

Prognostic value of lymph node ratio in stage IIIC epithelial ovarian cancer with node-positive in a SEER population-based study

To assess the prognostic value of the lymph node ratio (LNR) in patients with stage IIIC epithelial ovarian cancer (EOC) with node-positive in a Surveillance, Epidemiology, and End Results (SEER) population-based study. Data of patients were obtained from the SEER database from 1990 to 2012, and analyzed using Kaplan-Meier survival methods and Cox regression proportional hazard model. The prognostic value of the LNR on cause-specific survival (CSS) and overall survival (OS) were calculated. A total of 5,926 patients were identified. Univariate analysis showed that the number of removed lymph nodes (RLNs), the number of positive lymph nodes, and the LNR were significantly associated with CSS and OS (P < 0.05 for all). Multivariate analysis indicated that a higher LNR was an independent prognostic factor for poorer CSS (hazard ratio [HR]: 1.896, 95% confidence interval [CI]: 1.709-2.104, P < 0.001) and OS (HR:1.679, 95% CI: 1.454-1.939, P < 0.001). Among patients with LNR ≤ 0.42 and those with LNR > 0.42, the 5-year CSS was 53.1% and 34.7%, respectively (P < 0.001), and the 5-year OS was 50.4% and 32.0%, respectively (P < 0.001). The prognostic value of the LNR persisted for patients after stratification by the numbers of RLNs, tumor histology, and tumor grade. LNR is a more accurate prognostic method for stage IIIC EOC patients. Patients with a higher LNR are associated with poorer survival in stage IIIC EOC.

Prognosis of patients with esophageal squamous cell carcinoma after esophagectomy using the log odds of positive lymph nodes

To compare the log odds of positive lymph nodes (LODDS) with the number of positive lymph nodes (pN), lymph node ratio (LNR), removed lymph node (RLN) count, and negative lymph node (NLN) count in determining the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. The records of patients with ESCC who received esophagectomy were retrospectively reviewed. The log-rank test was used to compare curves for overall survival (OS), and Cox regression analysis was performed to identify prognostic factors. The prognostic performance of the different lymph node staging systems were compared using the linear trend chi-square test, likelihood ratio chi-square test, and Akaike information criterion. A total of 589 patients were enrolled. Univariate Cox analysis showed that pN stage, LNR, RLN count, NLN count, and the LODDS were significantly associated with OS (p < 0.05 for all). Multivariate Cox analysis adjusted for significant factors indicated that LODDS was independent risk factor on overall survival (OS), and a higher LODDS was associated with worse OS (hazard ratio = 3.297, 95% confidence interval: 2.684–4.050, p < 0.001). The modified Tumor-LODDS-Metastasis staging system had better discriminatory ability, monotonicity, and homogeneity, and better optimistic prognostic stratification than the Tumor-Node-Metastasis staging system in determining the prognosis of patients with ESCC. The LODDS staging system was superior to other lymph node classifications in determining the prognosis of patients with ESCC after esophagectomy. LODDS may be incorporated into esophageal staging system if these results are eventually confirmed by other studies.

Using the lymph nodal ratio to predict the risk of locoregional recurrence in lymph node-positive breast cancer patients treated with mastectomy without radiation therapy

BackgroundTo evaluate the prognostic value of axillary lymph node ratio (LNR) as compared to the number of involved nodes (pN stage) in patients with axillary lymph node-positive breast cancer treated with mastectomy without radiation.MethodsWe performed a retrospective analysis of the clinical data of patients with stage II-III node-positive breast cancer (N=1068) between 1998 and 2007. Locoregional recurrence-free survival (LRFS) and overall survival (OS) were compared based on the LNR and pN staging.ResultsA total of 780 cases were classified as pN1, 183 as pN2, and 105 as pN3. With respect to LNR, 690 cases had a LNR from 0.01-0.20, 269 cases a LNR from 0.21-0.65, and 109 cases a LNR > 0.65. The median follow-up time was 62 months. Univariate analysis showed that both LNR and pN stage were prognostic factors of LRFS and OS (p<0.05). Multivariate analysis indicated that LNR was an independent prognostic factor of LRFS and OS (p<0.05). pN stage had no significant effect on LRFS or OS (p>0.05). In subgroup analysis, the LNR identified groups of patients with different survival rates based on pN stage.ConclusionsLNR is superior to pN staging as a prognostic factor in lymph node-positive breast cancer after mastectomy, and should be used as one of the indications for adjuvant radiation therapy.

The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis:

To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer–specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2− and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor−/human epidermal growth factor receptor 2+ and hormone receptor−/human epidermal growth factor receptor 2− subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor−/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer–specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor−/human epidermal growth factor receptor 2− subtype conferred a significantly poorer outcome in terms of breast cancer–specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer–specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer–specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and liver metastases might be effective in improving breast cancer–specific survival and overall survival.

Patterns of distant metastasis in Chinese women according to breast cancer subtypes

To access possible relationships between breast cancer subtypes (BCS) and patterns of distant metastasis in advanced breast cancer. Breast cancer patients with distant metastasis at two academic centers from 2000-2015 were retrospectively reviewed. The breast cancer was classified into four subtypes: hormone receptor (HR) +/ human epidermal growth factor receptor 2 (HER2) − (i.e., estrogen receptor [ER] + and/or progesterone receptor [PR] +, HER2−); HR+/HER2+ (ER+ and/or PR+, HER2+), HR−/HER2+ (ER− and PR−, and HER2+); and HR−/HER2− (ER− and PR−, and HER2−). A total of 679 patients were identified. The distribution of the BCS was 39.9% (271/679), 23.7% (161/679), 16.8% (114/679), and 19.6% (133/679) in HR+/HER2−, HR+/HER2+, HR−/HER2+, and HR−/HER2−, respectively. Patients with HR+/HER2+ and HR−/HER2+ subtypes were prone to abdominal and pelvic metastasis, those with HR+/HER2− and HR+/HER2+ subtypes were prone to bone metastasis, while patients with the HR−/HER2− subtype were prone to lung/mediastinal and brain metastases. In patients with pleural, axillary and/or neck lymph node, and other distant soft tissue metastases, there was no significant difference in metastatic patterns among the BCS. There are different patterns of distant metastasis associated with different BCS. There should be a different focus in the postoperative follow-up and monitoring of breast cancer patients with different BCS.

Tailoring Pelvic Lymphadenectomy for Patients with Stage IA2, IB1, and IIA1 Uterine Cervical Cancer.

Purpose: The purpose of this study was to assess the risk factors for pelvic lymph node metastasis (PLNM) in patients with early-stage uterine cervical cancer. Methods: A total of 192 patients with early-stage uterine cervical cancer (FIGO stage IA2, IB1, and IIA1) receiving radical hysterectomy with pelvic lymphadenectomy were included in the statistical analysis. Results: Thirty-six patients (18.8%) developed PLNM, and the incidences of PLNM in patients with stage IA2, stage IB2, and stage IIA1 were 0% (0/6), 13.9% (20/144), and 38.1% (16/42), respectively. The most common location of PLNM was the obturator lymph node. Univariate analysis showed that stage IIA1 (p < 0.001), tumor size greater than 3 cm (p = 0.019), deep-full thickness stromal invasion (p < 0.001), and lymphovascular invasion (p = 0.001) were associated with PLNM. Multivariate analysis showed that deep or full-thickness stromal invasion and lymphovascular invasion were significantly and independently associated with PLNM (p < 0.05 for both). The incidence of PLNM was 34.9% and 28.7% in patients with deep-full thickness stromal invasion and lymphovascular invasion, respectively, but that was only 5.7% and 9.2% in patients with superficial-middle stromal invasion and absence of lymphovascular invasion, respectively. Conclusion: Patients with superficial-middle stromal invasion and without lymphovascular invasion may be avoided pelvic lymphadenectomy in stage IA2, IB1, IIA1 uterine cervical cancer.