Sex-Based Heterogeneity in the Clinicopathological Characteristics and Prognosis of Breast Cancer: A Population-Based Analysis

PurposeTo better understand the differences in clinicopathological features and prognosis between male breast cancer (MBC) and female breast cancer (FBC).Material and MethodsData on patients diagnosed with breast cancer from January 1, 2010, to December 31, 2016, were obtained from the Surveillance, Epidemiology, and End Results database. Selected patients were classified into MBC and FBC, of which population demographics and clinicopathological features at baseline were successively extracted for analysis. Comparative analysis was performed to explore the differences in baseline characteristics, followed by propensity-score matching to calibrate the objective distinctions for adjusted analysis. Survival analysis was carried out to investigate divergences presented in prognosis from the two cohorts, and risk factors for prognosis were successively identified using univariate and multivariate COX regression analyses.ResultsA total of 407341 individuals were eligible, including 3111 MBC (0.7%) and 404230 FBC (99.3%) patients. Comparatively, patients with MBC tended to be older at diagnosis, with a higher confirmation of ductal carcinoma, a higher histological grade, a higher TNM stage, a higher proportion of luminal-like subtype, a higher rate of lung metastasis, a lower incidence of liver involvement, and a lower rate of surgical, radiation, and chemotherapeutic delivery. The overall prognosis of MBC was significantly worse than that of FBC, with a decreasing divergence both in median overall survival (65.5 months vs. 72.7 months, P<0.0001) and median breast cancer-specific survival (75.4 months vs. 77.8 months, P<0.0001). However, these discrepancies were not consistent among patients from different subgroups stratified by molecular subtype, age at diagnosis, or disease stage.ConclusionIn this study, sex-based heterogeneity in clinicopathological characteristics and prognostic profiles was observed in the overall population of patients with breast cancer and was significantly variable among different subgroups. A male-specific design with reasonable endpoints for a clinical trial protocol will be warranted in the future.

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Overall and Cancer-Specific Survival of Patients With Breast, Colon, Kidney, and Lung Cancers With and Without Chronic Lymphocytic Leukemia: A SEER Population-Based Study

Journal of Clinical Oncology ◽

10.1200/jco.2012.43.4449 ◽

2013 ◽

Vol 31 (7) ◽

pp. 930-937 ◽

Cited By ~ 35

Author(s):

Benjamin M. Solomon ◽

Kari G. Rabe ◽

Susan L. Slager ◽

Jerry D. Brewer ◽

James R. Cerhan ◽

...

Keyword(s):

Breast Cancer ◽

Chronic Lymphocytic Leukemia ◽

Population Based ◽

Lymphocytic Leukemia ◽

Disease Stage ◽

Tumor Type ◽

Cancer Specific Survival ◽

Lung Cancers ◽

Increased Risk ◽

A Site

Purpose Chronic lymphocytic leukemia (CLL) is associated with an increased risk of developing second cancers. However, it is unknown whether CLL alters the disease course of these cancers once they occur. Patients and Methods All patients with cancers of the breast (n = 579,164), colorectum (n = 412,366), prostate (n = 631,616), lung (n = 489,053), kidney (n = 95,795), pancreas (n = 82,116), and ovary (n = 61,937) reported to the SEER program from 1990 to 2007 were identified. Overall survival (OS; death resulting from any cause) and cancer-specific survival were examined, comparing patients with and without pre-existing CLL. Cancer-specific survival was evaluated for each tumor type in a site-specific manner (eg, death resulting from breast cancer in a patient with breast cancer). Results Patients with cancers of the breast (hazard ratio [HR], 1.70; P < .001), colorectum (HR, 1.65; P < .001), kidney (HR, 1.54; P < .001), prostate (HR, 1.92; P < .001), or lung (HR, 1.19; P < .001) had inferior OS if they had a pre-existing diagnosis of CLL after adjusting for age, sex, race, and disease stage. These results for OS remained significant for patients with cancers of the breast, colorectum, and prostate after excluding or censoring CLL-related deaths. Cancer-specific survival was also inferior for patients with cancers of the breast (HR, 1.41; P = .005) and colorectum (HR, 1.46; P < .001) who had pre-existing CLL after adjusting for age, sex, race, and disease stage. Conclusion Inferior OS and cancer-specific survival was observed for several common cancers in patients with pre-existing CLL. Additional studies are needed to determine the optimal management of these malignancies in patients with CLL and whether more aggressive screening or alternative approaches to adjuvant therapy are needed.

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The effect of postmastectomy radiotherapy in node-positive triple-negative breast cancer

BMC Cancer ◽

10.1186/s12885-020-07639-x ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Lei Zhang ◽

Ru Tang ◽

Jia-Peng Deng ◽

Wen-Wen Zhang ◽

Huan-Xin Lin ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Cox Regression ◽

Population Based ◽

Breast Cancers ◽

Cancer Specific Survival ◽

Postmastectomy Radiotherapy ◽

Pathological Staging ◽

Node Positive ◽

Advanced Tumor

Abstract Background The value of postmastectomy radiotherapy (PMRT) for pathological node-positive triple-negative breast cancers (TNBC) remains debatable. The aim of this population-based retrospective study was to evaluate the effect of PMRT on survival outcomes in this population. Methods Patients diagnosed with stage T1-4N1-N3M0 TNBC between 2010 and 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We used univariate and multivariate Cox regression hazards method to determine the independent prognostic factors associated with 3-year breast cancer-specific survival (BCSS). The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. Results Of the 4398 patients included in this study, 2649 (60.2%) received PMRT. Younger age, black ethnicity, and advanced tumor (T) and nodal (N) stage were the independent predictors associated with PMRT receipt (all P < 0.05). Patients who received PMRT showed better 3-year BCSS (OR = 0.720, 95% CI = 0.642–0.808, P < 0.001) than those that did not. The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. The results showed that PMRT was associated with better 3-year BCSS in patients with stage T3–4N1 (P = 0.042), T1-4N2 (P < 0.001), and T1-4N3 (P < 0.001), while comparable 3-year BCSS was found between the PMRT and non-PMRT cohorts with T1–2N1 disease (P = 0.191). Conclusions Radiotherapy achieved better 3-year BCSS in TNBC patients with stage T3–4N1 and T1-4N2–3 disease. However, no survival benefit was found with the addition of PMRT in patients with T1–2N1 TNBC.

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Prognostic Value of LRG1 in Breast Cancer: A Retrospective Study

Oncology Research and Treatment ◽

10.1159/000510945 ◽

2020 ◽

pp. 1-6

Author(s):

Yan-Shou Zhang ◽

Lei Han ◽

Chao Yang ◽

Yun-Jiang Liu ◽

Xiang-Mei Zhang

Keyword(s):

Breast Cancer ◽

Early Breast Cancer ◽

Cox Regression ◽

Molecular Subtype ◽

Histological Grade ◽

Disease Free Survival ◽

Pathological Stage ◽

Tissue Samples ◽

Factors Affecting ◽

Elevated Expression

Background: High expression of leucine-rich alpha-2-glycoprotein 1 (LRG1) is closely related to angiogenesis, which may play an important role in promoting invasion and metastasis. However, the current literature has yet to clarify the clinical significance of LRG1 in breast cancer. Objectives: The purpose of this work was to validate the correlation between LRG1 expression and prognosis in early breast cancer. Methods: We utilized an LRG1 detection agent in 330 cases of early breast cancer. The correlation of LRG1 expression with clinicopathological features, patient recurrence, and survival was investigated. Results: Compared with adjacent tissue samples, an elevated expression of LRG1 was observed in breast cancer samples. Moreover, LRG1 expression is associated with the number of lymphatic metastases and TNM pathological stage (p = 0.000, p = 0.000, respectively). For disease-free survival (DFS), the Kaplan-Meier curve indicated a poorer prognosis for the group with high LRG1 levels compared with the low LRG1 group (p = 0.000). A similar result was found for overall survival (OS; p = 0.000). The multivariate Cox regression indicated that LRG1 was still associated with DFS (HR 2.090, 95% CI 1.205–3.625, p = 0.009) and OS (HR 2.112, 95% CI 1.167–3.822, p = 0.013). The histological grade, TNM pathological stage, and molecular subtype were identified as independent risk factors affecting OS. Conclusion: In the malignant progression of breast cancer, high LRG1 levels are associated with lymphatic metastasis, histological grade, poor DFS, and poor OS. This study validates the use of LRG1 as a potential prognosis biomarker for early breast cancer.

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Breast-Conserving Therapy Has Better Prognosis for Tumors in the Central and Nipple Portion of Breast Cancer Compared with Mastectomy: A SEER Data-Based Study

Frontiers in Oncology ◽

10.3389/fonc.2021.642571 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jing Wang ◽

Xiaoyu Wang ◽

Zhenyu Zhong ◽

Xue Li ◽

Jiazheng Sun ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Subtype ◽

Histological Grade ◽

Treatment Strategies ◽

Breast Conserving Therapy ◽

Breast Cancer Patients ◽

Cancer Specific Survival ◽

Kaplan Meier ◽

Seer Data ◽

Cox Proportional Hazard Models

Background and ObjectivesCurrently, the location of primary tumor was an independent prognostic factor of breast cancer. Tumors in the central and nipple portion (TCNP) had poor prognosis compared to other peripheral quadrants. The breast-conserving therapy (BCT) is becoming increasingly common worldwide in breast cancer operations. However, whether the availability of BCT was performed for TCNP remained a matter of debate. We sought to investigate whether BCT was suitable for TCNP with respect to survival outcomes, compared with mastectomy therapy.MethodsUtilizing the Surveillance, Epidemiology, and End Results (SEER) database, we obtained TCNP breast cancer patients diagnosed during the period of 2010–2015. One-to-one (1:1) propensity score matching (PSM) was applied to construct a matched sample consisting of pairs of BCT and mastectomy groups. Univariate and multivariate Cox proportional hazard models were applied to estimate the factors associated with breast cancer-specific survival (BCSS) and overall survival (OS). Survival analysis was performed with the Kaplan–Meier method.ResultsIn the overall cohort, a total of 9,900 patients were enrolled. We found that patients with BCT showed significantly better BCSS (log-rank, p < 0.001) and OS (log-rank, p < 0.001) than the mastectomy group before PSM. The same finding was also shown in 5,820 patients after PSM. Additionally, none of the subgroups, including age, sex, race, histological grade, AJCC stage, and molecular subtype undergoing mastectomy therapy, had better BCSS than BCT.ConclusionsOur study was the first research to show that BCT exhibited superior prognosis in the cohort of TCNP from SEER databases than mastectomy therapy. This finding could provide a cue for treatment strategies for suitable TCNP patients, especially those with a strong willingness to conserve their breasts.

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Prognostic significance of the chemokine CXCL13 in node-negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.615 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 615-615

Author(s):

Marcus Schmidt ◽

Leonie van de Sandt ◽

Daniel Boehm ◽

Isabel Sicking ◽

Marco Johannes Battista ◽

...

Keyword(s):

Breast Cancer ◽

Cox Regression ◽

Molecular Subtype ◽

Histological Grade ◽

Meta Analysis ◽

Prognostic Significance ◽

Her2 Status ◽

Node Negative ◽

Node Negative Breast Cancer ◽

Independent Prognostic Significance

615 Background: The chemokine CXCL13 is chemotactic for B cells. We examined the prognostic significance of CXCL13 mRNA expression in node-negative breast cancer. Methods: Microarray based gene-expression data for CXCL13 (205242_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of CXCL13 on metastasis-free survival (MFS) was examined in the whole cohort and in different molecular subtypes (ER+/HER2-, ER-/HER2-, HER2+). Independent prognostic relevance was analysed using multivariate Cox regression. Results: Higher RNA expression of CXCL13 was related to better MFS in a meta-analysis of the whole cohort (HR 0.88, 95% CI 0.83-0.94, P<0.0001). Prognostic significance was most pronounced in the HER2+ positive molecular subtype (HR 0.72, 95% CI 0.59-0.87, P=0.0009) as compared to ER+/HER2- (HR 0.86, 95% CI 0.76-0.98, P=0.0024) and ER-/HER2- (HR 0.85, 95% CI 0.75-0.98), P=0.02) carcinomas of the breast. CXCL13 showed independent prognostic significance (HR 0.81, 95% CI 0.7336 0.8982, P=0.0001) in multivariate analysis. In addition to CXCL13, only histological grade of differentiation (HR 2.20, 95% CI 1.41-3.42, P=0.0005) and tumor size (HR 1.72, 95% CI 1.13-2.61, P=0.012), but neither age nor HER2 status nor hormone receptor status retained an independent prognostic association with MFS. Conclusions: The chemokine CXCL13 has independent prognostic significance in node-negative breast cancer. Higher expression of CXCL13 is associated with improved outcome.

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Adenosquamous carcinoma of the breast: a population-based study

Breast Cancer ◽

10.1007/s12282-021-01222-3 ◽

2021 ◽

Author(s):

Cheng Xu ◽

Zhangyuan Gu ◽

Juan Liu ◽

Xiaoyan Lin ◽

Cheng Wang ◽

...

Keyword(s):

Breast Cancer ◽

Hormone Receptors ◽

Adenosquamous Carcinoma ◽

Histological Grade ◽

Population Based ◽

Clinicopathological Characteristics ◽

Breast Cancer Patients ◽

Duct Carcinoma ◽

Population Based Study ◽

Significant Difference

Abstract Background To summarize the clinicopathological characteristics, prognosis, and management of breast adenosquamous carcinoma (ASC). Methods A population-based study was performed using retrospectively extracted data from the Surveillance, Epidemiology, and End Results database for breast cancer patients with histological diagnoses of ASC, infiltrating duct carcinoma (IDC) and squamous cell carcinoma (SCC) from 2004 to 2016. Results ASC presented similar tumor size but low histological grade and less lymph node metastasis compared to IDC. ASC expressed less positive rate of hormone receptors and barely HER2, which was similar with SCC. ASC patients underwent the similar surgical and systematic treatment as IDC, only with less radiotherapy. Median follow-up data of 78 months showed that the prognosis of IDC patients was better than that of ASC patients (all p < 0.05 for BCSM and OS). ASC was not an independent prognosis factor of breast cancer. After propensity score matching (PSM), no significant difference in BCSM nor OS was observed between ASC and IDC groups. In HR-negative patients, the prognosis of ASC was similar with that of IDC, and both were superior to SCC. In HR-positive patients, the 5-year survival rate of ASC was 63.5%, which was far less than that in ASC of HR-negative (81.0%). Multivariate analysis showed that older age (age > 60) and advanced AJCC-stage were independent factors of poor prognosis in ASC, breast-conserving surgery was also ideally suited for ASC. Conclusions ASC has unique clinicopathological characteristics and prognosis. It is imperative to focus on a more precise and personalized treatment management of ASC patients.

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Molecular Subtype May Be More Associated With Prognosis and Chemotherapy Benefit Than Tumor Size in T1N0 Breast Cancer Patients: An Analysis of 2,168 Patients for Possible De-Escalation Treatment

Frontiers in Oncology ◽

10.3389/fonc.2021.636266 ◽

2021 ◽

Vol 11 ◽

Author(s):

Siji Zhu ◽

Yafen Li ◽

Weiguo Chen ◽

Xiaochun Fei ◽

Kunwei Shen ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Size ◽

Proportional Hazards ◽

Cox Regression ◽

Molecular Subtype ◽

Growth Factor Receptor ◽

Disease Free Survival ◽

Cox Proportional Hazards ◽

Breast Cancer Patients ◽

Cancer Specific Survival

PurposeBreast cancer (BC) patients with T1N0 tumors have relatively favorable clinical outcomes. However, it remains unclear whether molecular subtypes can aide in prognostic prediction for such small, nodal-negative BC cases and guide decision-making about escalating or de-escalating treatments.Patients and MethodsT1N0 BC patients diagnosed between 2009 and 2017 were included and classified into three subgroups according to receptor status: 1) hormonal receptor (HR)+/human epidermal growth factor receptor-2 (HER2)−; 2) HER2+; and 3) triple negative (TN) (HR−/HER2−). Patients’ characteristics and relapse events were reviewed. Kaplan–Meier analysis and Cox regression were used to assess the iDFS and BCSS. The effects of risk factors and adjuvant treatment benefits were evaluated by calculating hazard ratios (HRs) for invasive disease-free survival (iDFS) and breast cancer-specific survival (BCSS) with Cox proportional hazards models.ResultsIn total, 2,168 patients (1,435 HR+/HER2−, 427 HER2+, 306 TN) were enrolled. The 5-year iDFS rates were 93.6, 92.7, and 90.6% for HR+/HER2−, HER2+, and TN patients, respectively (P = 0.039). Multivariate analysis demonstrated that molecular subtype (P = 0.043), but not tumor size (P = 0.805), was independently associated with iDFS in T1N0 BC. TN patients [HRs = 1.77, 95% confidence interval (CI) = 1.11–2.84, P = 0.018] had a higher recurrence risk than HR+/HER2− patients. Adjuvant chemotherapy benefit was not demonstrated in all T1N0 patients but interacted with molecular subtype status. TN (adjusted HRs = 2.31, 95% CI = 0.68–7.54) and HER2+ (adjusted HRs = 2.26, 95% CI = 0.95–5.63) patients receiving chemotherapy had superior iDFS rates. Regarding BCSS, molecular subtype tended to be related to outcome (P = 0.053) and associated with chemotherapy benefit (P = 0.005).ConclusionMolecular subtype was more associated with disease outcome and chemotherapy benefit than tumor size in T1N0 BC patients, indicating that it may guide possible clinical de-escalating therapy in T1N0 BC.

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Gastric adenocarcinoma in young patients: A population-based appraisal

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4547 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4547-4547

Author(s):

W. B. Al-Refaie ◽

P. W. Pisters ◽

G. J. Chang

Keyword(s):

Gastric Cancer ◽

Gastric Adenocarcinoma ◽

Cox Regression ◽

Young Patients ◽

Stage Iv ◽

Population Based ◽

Disease Stage ◽

Lower Grade ◽

Cancer Specific Survival ◽

Population Based Study

4547 Background: While gastric adenocarcinoma is uncommon in young patients, reports of their outcomes remain inconsistent. We performed a population-based study of survival outcomes for gastric cancer in young adults (<45 years). Methods: Patients with gastric adenocarcinoma who underwent cancer directed surgery were identified from the Surveillance Epidemiology and End Results registry from 1991 to 2002. Patient demographics, tumor grade, AJCC stage and use of radiation were categorized by age to <45 years, 45 to 70 years and >70 years old. Cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis with log rank comparisons. Cox multiple regression analysis was performed to adjust for confounder effects. Results: A total of 20,830 patients were identified: 1,051 (5%) <45 years old [Grp 1], 8,456 (40.6%) 45–70 years old [Grp 2], and 11,323 (54.4%) >70 years old [Grp 3]. Grp 1 was more likely than Grp 2 to have advanced nodal disease (multinomial odds ratio [OR]=1.5 for N2 vs N0, 95% confidence interval [CI] 1.14–2.0, p=0.004; OR=2.0 for N3 vs N0, CI 1.4–3.0, p=0.0002) and more likely to have metastases at presentation (OR 1.5, p<0.00001). Stage-stratified 3-year cancer- specific survival [CSS] was not associated with age at diagnosis except for stage IV disease ( Table ). On Cox regression, young age did not impact survival (OR 0.95, CI 0.87–1.03, p=0.19). However, female gender, Asian race, earlier disease stage, lower grade, cancer- directed surgery and use of radiotherapy were predictors of better outcome (all p=0.003). Conclusions: Although young patients with gastric cancer in this population-based study present with more advanced disease, their stage-stratified cancer specific survival is similar to that of older patients. Stage-dependent, but not age-dependent, treatment should therefore be performed in young patients with gastric cancer. [Table: see text] No significant financial relationships to disclose.

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Tumor collagen framework from bright-field histology images predicts overall survival of breast carcinoma patients

Scientific Reports ◽

10.1038/s41598-021-94862-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mindaugas Morkunas ◽

Dovile Zilenaite ◽

Aida Laurinaviciene ◽

Povilas Treigys ◽

Arvydas Laurinavicius

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Cancer Patient ◽

Breast Cancer Patient ◽

Cox Regression ◽

Regional Lymph Node ◽

Histological Grade ◽

Biological Information ◽

Lymph Node Status ◽

Bright Field

AbstractWithin the tumor microenvironment, specifically aligned collagen has been shown to stimulate tumor progression by directing the migration of metastatic cells along its structural framework. Tumor-associated collagen signatures (TACS) have been linked to breast cancer patient outcome. Robust and affordable methods for assessing biological information contained in collagen architecture need to be developed. We have developed a novel artificial neural network (ANN) based approach for tumor collagen segmentation from bright-field histology images and have tested it on a set of tissue microarray sections from early hormone receptor-positive invasive ductal breast carcinoma stained with Sirius Red (1 core per patient, n = 92). We designed and trained ANNs on sets of differently annotated image patches to segment collagen fibers and extracted 37 features of collagen fiber morphometry, density, orientation, texture, and fractal characteristics in the entire cohort. Independent instances of ANN models trained on highly differing annotations produced reasonably concordant collagen segmentation masks and allowed reliable prognostic Cox regression models (with likelihood ratios 14.11–22.99, at p-value < 0.05) superior to conventional clinical parameters (size of the primary tumor (T), regional lymph node status (N), histological grade (G), and patient age). Additionally, we noted statistically significant differences of collagen features between tumor grade groups, and the factor analysis revealed features resembling the TACS concept. Our proposed method offers collagen framework segmentation from bright-field histology images and provides novel image-based features for better breast cancer patient prognostication.

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Effects of marital status on overall and cancer-specific survival in laryngeal cancer patients: a population-based study

Scientific Reports ◽

10.1038/s41598-020-80698-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhao Ding ◽

Deshun Yu ◽

Hefeng Li ◽

Yueming Ding

Keyword(s):

Marital Status ◽

Cancer Patients ◽

Laryngeal Cancer ◽

Cox Regression ◽

Group Analysis ◽

Population Based ◽

Cancer Specific Survival ◽

Cox Regression Analysis ◽

Prognostic Effect ◽

The Difference

AbstractMarital status has long been recognized as an important prognostic factor for many cancers, however its’ prognostic effect for patients with laryngeal cancer has not been fully examined. We retrospectively analyzed 8834 laryngeal cancer patients in the Surveillance Epidemiology and End Results database from 2004 to 2010. Patients were divided into four groups: married, widowed, single, and divorced/separated. The difference in overall survival (OS) and cancer-specific survival (CSS) of the various marital subgroups were calculated using the Kaplan–Meier curve. Multivariate Cox regression analysis screened for independent prognostic factors. Propensity score matching (PSM) was also conducted to minimize selection bias. We included 8834 eligible patients (4817 married, 894 widowed, 1732 single and 1391 divorced/separated) with laryngeal cancer. The 5-year OS and CSS of married, widowed, single, and separated/divorced patients were examined. Univariate and multivariate analyses found marital status to be an independent predictor of survival. Subgroup survival analysis showed that the OS and CSS rates in widowed patients were always the lowest in the various American Joint Committee on Cancer stages, irrespective of sex. Widowed patients demonstrated worse OS and CSS in the 1:1 matched group analysis. Among patients with laryngeal cancer, widowed patients represented the highest-risk group, with the lowest OS and CSS.

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