Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative () and positive () lymph node status matched for possible confounding factors were subjected to laser microdissection and gene expression data generated. Although ANOVA analysis (, fold-change >1.5) revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis.

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Benefit of chemotherapy differs in node-negative and node-positive stage III nasopharyngeal carcinoma: analysis of the SEER database

10.21203/rs.3.rs-275893/v1 ◽

2021 ◽

Author(s):

Zhen-Fei Xiang ◽

Dan-Fei Hu ◽

Hua-Cai Xiong ◽

Ming-Yao Li ◽

Zhan-Chun Zhang ◽

...

Keyword(s):

Lymph Node ◽

Nasopharyngeal Carcinoma ◽

Survival Benefit ◽

Hazard Ratio ◽

Stage Iii ◽

Lymph Node Status ◽

Seer Database ◽

Node Negative ◽

Node Positive ◽

Node Status

Abstract Objectives: Chemoradiotherapy is the standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). We aimed to reveal factors associated with chemotherapy use and evaluate chemotherapy's benefit in patients with stage III NPC stratified by lymph node status. Patients and Methods: Overall, 1,452 patients with stage III NPC who underwent radiotherapy with (n=1361) or without (n=91) chemotherapy were identified in the SEER database. We identified predictors for chemotherapy use using logistic regression analysis. We compared all-cause mortality (ACM) and cancer-specific mortality (CSM) using Kaplan-Meier method. Cox regression and competing risk analyses were used to evaluate chemotherapy benefit. The inverse probability of treatment weighting (IPTW) approach was applied to reduce selection bias and adjust for competing risks. Subgroup analyses and interaction effects were explored.Results: Factors including age, sex, insured status, tumor grade, and N category were associated with chemotherapy use. Chemotherapy was associated with decreased 5-year ACM (31.4% vs. 48.4%, p<0.001) and CSM (25.5% vs. 35.8%; p=0.017) in stage III NPC patients. The IPTW-adjusted hazard ratio for 5-year ACM was 0.57 (95% CI: 0.38–0.86, p=0.008), whereas IPTW-adjusted sub-hazard ratio for 5-year CSM was 0.62 (95% CI: 0.42–0.93, p=0.003). A significant interaction effect existed between lymph node status and treatment modality. Chemotherapy offered a significant survival benefit in node-positive stage III NPC. However, no chemotherapy benefit for the node-negative disease was observed.Conclusion: Chemotherapy adds survival benefit in stage III NPC, especially in patients with node-positive disease. The magnitude of chemotherapy benefit in node-negative stage III NPC warrants further investigation.

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