Factors associated with better overall survival (OS) in patients with previously treated, PD-L1–expressing, advanced NSCLC: Multivariate analysis of KEYNOTE-010.

9090 Background: We identified factors associated with better OS for previously treated, PD-L1–expressing advanced NSCLC using data from KEYNOTE-010 (NCT01905657; Herbst et al. Lancet. 2016;387:1540-50), in which pembrolizumab had superior OS over docetaxel. Methods: 1033 patients were randomly assigned 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or docetaxel 75 mg/m2 Q3W. Response was assessed per RECIST v1.1 by independent central review. Multivariate analyses were performed using a Cox proportional hazards regression model on OS in the pembrolizumab arms. A set of variable selection methods was applied to 19 baseline demographic and disease characteristics, including smoking status, and identified 7 factors that contributed to OS. Data cut was September 30, 2016. Results: Adjusted hazard ratios (HRs) for the factors in the pembrolizumab arm from the model are shown in the Table. Updated OS with an additional 6 months of follow-up from this data lock for KEYNOTE-010 will be presented. Conclusions: While the overall result of KEYNOTE-010 revealed improved OS with pembrolizumab compared with docetaxel in previously treated patients with PD-L1–positive advanced NSCLC, exploratory, post hoc multivariate analyses showed that some laboratory and tumor characteristics such as nonsquamous histology, normal baseline lactate dehydrogenase (LDH), PD-L1 TPS ≥50%, and wild-type EGFR mutation status were associated with better OS among patients treated with pembrolizumab. Clinical trial information: NCT01905657. [Table: see text]

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Comparison of outcomes with pembrolizumab monotherapy (P) versus combination with chemotherapy (P+C) in advanced non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21579 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21579-e21579

Author(s):

Kartik Sehgal ◽

Ritu R. Gill ◽

Poorva Bindal ◽

Anita Geevarghese Koshy ◽

Danielle C McDonald ◽

...

Keyword(s):

Proportional Hazards ◽

Advanced Nsclc ◽

Proportional Hazards Model ◽

Smoking Status ◽

Performance Status ◽

Objective Response ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Phase Iii ◽

Ecog Performance Status

e21579 Background: P and P+C are standard-of-care (SOC) treatment options for advanced NSCLC. However, they have not yet been directly compared in clinical trials. Methods: We conducted a retrospective cohort study of patients with advanced NSCLC who initiated treatment with SOC P±C at our center from 2/11/16 to 10/15/19 (data cutoff 1/15/20). Patient demographic, clinicopathologic, therapeutic and outcomes data were extracted. All radiographic scans were independently evaluated by a thoracic radiologist using iRECIST. Survival time was defined from the start of P±C. Kaplan-Meier and Cox proportional hazards model were utilized. Results: Of 103 patients with median follow up of 17.7 months, 74 (71.8%) had received P, while 29 (28.2%) had received P+C. In PD-L1 tumor proportion score (TPS) unselected population, there were no significant differences in age, sex, smoking status, driver mutation, tumor mutational burden (TMB), line of therapy, ECOG performance status (PS) or immune-related adverse events (irAE) between P and P+C groups. 71.6% in P vs 13.8% in P+C had PD-L1 TPS ≥50% (p < 0.001). There were no significant differences between the two groups in objective response rate (ORR), disease control rate (DCR), unadjusted progression-free survival (PFS) or unadjusted overall survival (OS) (Table). Multivariable adjustment for confounding factors between P+C vs P revealed no differences in OS [hazard ratio (HR) for death, 1.53, 95% CI 0.55 – 4.25] or PFS [HR for progression/death, 1.75, 95% CI 0.63 – 4.91]. Further stratification into PD-L1 TPS ≥50% and < 50% showed no significant differences between P+C vs. P in adjusted OS [HR for death, TPS < 50%- 1.54 (95% CI 0.59 – 4.03); TPS ≥50%- 0.71 (95% CI 0.11 – 4.52)] or PFS [HR for progression/death, TPS < 50%- 1.58 (95% CI 0.72 – 3.48); TPS ≥50%- 0.64 (95% CI 0.06 – 6.93)]. ECOG PS and development of irAE influenced OS in all groups, while TMB was relevant in PD-L1 ≥50% only. Conclusions: Our study shows no significant differences in outcomes with P vs P+C in advanced NSCLC in a real-world setting, albeit with limitations of single-center design, limited sample size, different line settings and lack of disease burden stratification. Ongoing phase III trials comparing front line P vs P+C will definitively address the long-term clinical benefits -if any- of combining cytotoxic chemotherapy with anti-PD-1 drugs. [Table: see text]

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Dietary Acrylamide Intake and Risk of Lung Cancer: The Japan Public Health Center Based Prospective Study

Nutrients ◽

10.3390/nu12082417 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2417

Author(s):

Rong Liu ◽

Ling Zha ◽

Tomotaka Sobue ◽

Tetsuhisa Kitamura ◽

Junko Ishihara ◽

...

Keyword(s):

Public Health ◽

Lung Cancer ◽

Prospective Study ◽

Health Center ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Public Health Center ◽

Hazard Ratios ◽

Dietary Acrylamide ◽

Using Data

Acrylamide, which forms in heat-treated foods with high carbohydrate content, is a probable human carcinogen. This study aimed to evaluate the association between dietary acrylamide intake and lung cancer using data from the Japan Public Health Center based Prospective Study. Our study included 85,303 participants who completed a food frequency questionnaire. Cox proportional hazards regression models were used to assess hazard ratios and 95% confidence intervals (CIs) after adjusting for confounders. After 14.3 years and 15.4 years of mean follow-up period, 1187 and 485 lung cancer cases were identified in men and women, respectively. The multivariable-adjusted hazard ratios of 10-µg/day increment in acrylamide intake were 1.01 (95% CI, 0.99–1.02) in men and 0.98 (95% CI, 0.95–1.02) in women. Compared with the lowest quartile of acrylamide intake, the hazard ratios for the highest quartile were 1.13 (95% CI, 0.95–1.33; p for trend = 0.12) in men and 1.03 (95% CI, 0.78–1.36; p for trend = 0.86) in women in the multivariable-adjusted model. Moreover, there was also no significant association observed in the stratified analysis for histological subtypes of lung cancer. This study demonstrated that dietary acrylamide intake was not associated with increased lung cancer risk in the Japanese population.

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Circulating CD52 and CD20 Levels Predict for Progression and Survival in Patients with CLL Treated with Fludarabine (F), Cyclophosphamide (C), and Rituximab (FCR).

Blood ◽

10.1182/blood.v108.11.2330.2330 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2330-2330

Author(s):

Gheath Alatrash ◽

Michael J. Keating ◽

Susan O’Brien ◽

Xuemei Wang ◽

Taghi Manshouri ◽

...

Keyword(s):

Multivariate Analysis ◽

Proportional Hazards ◽

Residual Disease ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Previously Treated Patients ◽

Previously Treated ◽

Univariate Analyses

Abstract The CD52 and CD20 antigens are ubiquitously expressed on CLL B cells and are important therapeutic targets for the monoclonal antibodies alemtuzumab and rituximab, respectively. Circulating soluble CD52 (sCD52) and CD20 (sCD20) have been shown to have prognostic value in CLL, non-Hodgkin’s lymphoma and Hodgkin’s disease (Blood101:2507, 2003; Br J Haem123:850, 2003). The pharmacokinetics and therapeutic efficacy of these mAbs may be adversely affected by circulating sCD52 and sCD20. Using the previously described ELISAs, we measured levels of sCD52 and sCD20 at various time points in blood (PB) and bone marrow (BM) of chemotherapy-naïve patients treated with FCR. Treatment consisted of fludarabine 25 mg/m2 d1-3, cyclophosphamide 250mg/m2 d1-3, and rituximab 375–500mg/m2 d1 as previously described (JCO23:4079, 2005). Courses were repeated every 4 weeks for a total of 6 courses. Univariate and multivariate Cox proportional hazards models were fit to evaluate the correlations of sCD52 and sCD20 and baseline characteristics with progression free survival (PFS) and overall survival (OS). A total of 291 patients were included, pretreatment characteristics [median (range)] were as follows: age=57yrs (17–86); WBC=76.9K/μL(2.1–619.5); ALC=66.7K/μL(0.8–558); HGB=12.4g/dL(6.1–18.7); PLT=155K/μL(8–406); ß2M= 3.7mg/L(1.6–16.4); LDH=550 IU/L(103–1828). Patients with Rai stage 0=8; I–II=186; and III–IV=97. The median follow-up time for all patients is 56 months. Of the 278 responding patients, 88 (31.7%) have progressed; the median time to progression has not been reached. To date, the median survival time for the 291 patients has not been reached; 57 (19.6%) patients have died. Pretreatment characteristics analyzed included age, gender, PS, WBC, ALC, HGB, PLT, ß2M, and RAI stage; post-treatment factors included PCR for IgVH in BM, and sCD52 and sCD20 (BM and PB) levels at response. Univariate analyses identified the following predictors for PFS (p < .05): age, HGB, ß2M, PCR for IgVH at response, and PB sCD20 at response. Independent predictors for PFS identified in multivariate analysis included PCR for IgVH and PB sCD20 level at response. For OS, significant (p < .05) factors in univariate analyses included: age, HGB, ß2M, PCR for IgVH at response, and BM sCD52 at response. Independent predictors for OS identified in multivariate analysis included age and BM sCD52 level at response. Residual sCD52 at response may reflect residual disease, therefore correlating with shorter OS. We are currently evaluating sCD52 and sCD20 as prognostic factors for clinical outcomes in previously treated patients that received FCR as salvage therapy.

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Cardiorespiratory Fitness without Exercise Testing Can Predict All-Cause Mortality Risk in a Representative Sample of Korean Older Adults

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16091633 ◽

2019 ◽

Vol 16 (9) ◽

pp. 1633 ◽

Cited By ~ 2

Author(s):

Moongu Song ◽

Inhwan Lee ◽

Hyunsik Kang

Keyword(s):

Older Adults ◽

Cardiorespiratory Fitness ◽

Exercise Testing ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Geriatric Population ◽

Hazard Ratios ◽

All Cause Mortality ◽

Using Data

This study examined the association between cardiorespiratory fitness (CRF) without exercise testing and all-cause mortality in Korean older adults. The present study was carried out using data from the 2008 and 2011 Living Profiles of Older People Survey. A total of 14,122 participants aged 60 years and older (57% women) completed the 2008 baseline and 2011 follow-up assessments (i.e., socioeconomic status, health behaviors and conditions, and prevalence of chronic diseases), and they were included for the final analyses. CRF was estimated (eCRF) with sex-specific algorithms and classified as lower (lowest 25%), middle (middle 50%), and upper (highest 25%). Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) across eCRF categories. In total, multivariable-adjusted HRs and 95% CIs were 1 for the upper eCRF group (referent), 1.059 (0.814~1.378) for the middle eCRF group, and 1.714 (1.304~2.253) for the lower eCRF group. In men, multivariable-adjusted HRs and 95% CIs were 1 for the upper eCRF group (referent), 1.011 (0.716~1.427) for the middle eCRF group, and 1.566 (1.098~2.234) for the lower eCRF group. In women, multivariable-adjusted HRs and 95% CIs were 1 for the upper eCRF group (referent), 1.064 (0.707~1.602) for the middle eCRF group, and 1.599 (1.032~2.478) for the lower eCRF group. The current findings suggest that eCRF may have an independent predictor of all-cause mortality, underscoring the importance of promoting physical activity to maintain a healthful level of CRF in Korean geriatric population.

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Use of disease-modifying antirheumatic drugs and the subsequent risk of herpes zoster in older adults

Rheumatology ◽

10.1093/rheumatology/keab538 ◽

2021 ◽

Author(s):

Jiahui Qian ◽

Marissa Nichole Lassere ◽

Anita Elizabeth Heywood ◽

Bette Liu

Keyword(s):

Herpes Zoster ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Antiviral Therapies ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Using Data ◽

Subsequent Risk

Abstract Objectives To examine the association between DMARD use and subsequent risk of herpes zoster in a large, heterogeneous, and prospective population-based cohort. Methods Using data from a cohort of adults (45 and Up Study) recruited between 2006 and 2009 and linked to pharmaceutical, hospital and death data (2004–2015), the effect of DMARD use on zoster risk was analysed using Cox proportional hazards models, adjusting for sociodemographic characteristics, comorbidities and corticosteroid use. Results Among 254 065 eligible participants, over 1,826 311 person-years follow-up, there were 6295 new DMARD users and 17 024 incident herpes zoster events. Compared with non-users, the risk of zoster was higher in those who used bDMARDs, either alone or in combination with csDMARDs than in those who only used csDMARDs (adjusted hazard ratios, aHR 2.53 [95% confidence interval, CI 2.03–3.16]) for bDMARDs vs 1.48 [95%CI 1.33–1.66] for csDMARDs, p-heterogeneity < 0.001; reference: non-users). Among users of csDMARDs, compared with non-users, zoster risks were highest in those using exclusively cyclophosphamide (aHR 2.69 [95%CI 1.89–3.83]), more moderate in those using azathioprine (aHR 1.57 [95%CI 1.07–2.30]) and hydroxychloroquine (aHR 1.43 [95%CI 1.11–1.83]) and not elevated in users of methotrexate (aHR 1.24 [95%CI 0.98–1.57]), sulfasalazine (aHR 1.00 [95%CI 0.71–1.42]) and leflunomide (aHR 0.41 [95%CI 0.06–2.88]). Conclusions The risk of zoster was high among bDMARD and cyclophosphamide users. Also, the risk was increased in those using hydroxychloroquine alone and in combination with methotrexate but not methotrexate alone. Preventative strategies such as zoster vaccination or antiviral therapies should be considered in these populations if not contraindicated.

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Abstract 015: Very-High Levels of HDL-C and Risks for CHD: The Lifetime Risk Pooling Project

Circulation ◽

10.1161/circ.125.suppl_10.a015 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

John T Wilkins ◽

Hongyan Ning ◽

Alan R Dyer ◽

Donald M Lloyd-Jones

Keyword(s):

Proportional Hazards ◽

Smoking Status ◽

A Priori ◽

Cox Proportional Hazards ◽

Point Estimate ◽

Atherosclerosis Risk In Communities ◽

Cox Proportional Hazards Models ◽

Chd Risk ◽

Hazard Ratios ◽

Very High

Background: Whereas observational cohort data suggest the association between HDL-C and coronary heart disease (CHD) is inverse and linear, data are sparse at HDL-C values > 80mg/dL. Methods: We therefore pooled data from the NHLBI public-funded datasets of the Framingham, Framingham Offspring, and Atherosclerosis Risk in Communities studies. We used multivariable Cox Proportional-Hazards Models to adjust for age, systolic blood pressure, body mass index, smoking status, prevalent diabetes, non-HDL-C, antihypertension and lipid medication use. We calculated adjusted hazard ratios (HR) to assess the association between a priori strata of HDL-C (<30; >30-40; >40-50; >50-60; >60-70; >70-80; >80mg/dL) and CHD death and non-fatal myocardial infarction using HDL-C >40-50mg/dL as the referent. Results: Over 118,716 person*years of follow up, there were 562 events in 9,226 participants. As expected, hazard ratios for CHD events are greatest in the lowest category of HDL-C (HR 1.68, 95%CI: 1.31, 2.21) and there was generally a stepwise inverse trend in CHD hazards up to 80mg/dL. (See Figure) At HDL-C > 80mg/dL the hazard point estimate for CHD events was insignificantly higher (HR 0.52, 95% CI 0.29, 0.95) than the hazard observed at HDL-C >70-80mg/dl (HR 0.35, 95% CI 0.18-0.66). However, the hazard for CHD events for HDL-C > 80mg/dL was still significantly lower than the referent. Conclusions: These data suggest that the association between HDL-C and CHD risk may not be inverse and linear at HDL-C values > 80mg/dL. These data support investigation into qualitative differences in HDL molecules in individuals with very high levels of HDL-C.

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Clinical Factors and Outcomes Associated With Immune Non-response Among Virally Suppressed Adults With HIV From Africa and the United States

10.21203/rs.3.rs-257710/v1 ◽

2021 ◽

Author(s):

Adi Noiman ◽

Allahna Esber ◽

Xun Wang ◽

Emmanuel Bahemana ◽

Yakubu Adamu ◽

...

Keyword(s):

Proportional Hazards ◽

Age Groups ◽

The United States ◽

Cox Proportional Hazards ◽

People Living With Hiv ◽

Clinical Factors ◽

Factors Affecting ◽

Factors Associated ◽

Hazard Ratios ◽

Before And After

Abstract Background: A significant minority of people living with HIV (PLWH) achieve viral suppression (VS) on antiretroviral therapy (ART) but do not regain healthy CD4 counts. Clinical factors affecting this immune non-response (INR) and its effect on incident serious non-AIDS events (SNAEs) have been challenging to understand due to confounders that are difficult to control in many study settings. Setting: The U.S. Military HIV Natural History Study (NHS) and African Cohort Study (AFRICOS). Methods: PLWH with sustained VS (<400 copies/mL for at least two years) were evaluated for INR (CD4 < 350 cells/µl at the time of sustained VS). Logistic regression estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with INR. Cox proportional hazards regression produced adjusted hazard ratios (aHRs) for factors associated with incident SNAE after sustained VS. Results: INR prevalence was 10.8% and 25.8% in NHS and AFRICOS, respectively. Higher CD4 nadir was associated with decreased odds of INR (aOR=0.31 [95% CI: 0.26, 0.37] and aOR=0.50 [95% CI: 0.43, 0.58] per 100 cells/µl in NHS and AFRICOS, respectively). After adjustment, INR was associated with a 61% increase in relative risk of SNAE [95% CI: 1.12, 2.33]. Probability of "SNAE-free" survival at 15 years since sustained VS was approximately 20% lower comparing those with and without INR; nearly equal to the differences observed by 15-year age groups. Conclusion: CD4 monitoring before and after VS is achieved can help identify PLWH at risk for INR. INR may be a useful clinical indicator of future risk for SNAEs.

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Outcomes of anti-PD-(L1) therapy in combination with chemotherapy versus immunotherapy (IO) alone for first-line (1L) treatment of advanced non-small cell lung cancer (NSCLC) with PD-L1 score 1-49%: FDA pooled analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9001 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9001-9001

Author(s):

Oladimeji Akinboro ◽

Jonathon Joseph Vallejo ◽

Pallavi Shruti Mishra-Kalyani ◽

Erin A. Larkins ◽

Nicole Lauren Drezner ◽

...

Keyword(s):

Proportional Hazards ◽

Advanced Nsclc ◽

Immune Cell ◽

Smoking Status ◽

Pooled Analysis ◽

Cox Proportional Hazards ◽

Therapeutic Options ◽

Survival Times ◽

Treatment Regimens ◽

Cox Proportional Hazards Models

9001 Background: IO + chemotherapy ± anti-angiogenics comprise FDA-approved 1L regimens for metastatic NSCLC, with IO-only therapy approved only for PD-L1-positive NSCLC. Patients with PD-L1 scores 1-49% have many therapeutic options, and little is known about how subgroups of patients experience benefit across treatment regimens. Methods: Data was pooled from 8 randomized controlled trials investigating anti-PD-(L)1 therapy as IO-only or in chemo-IO regimens for the 1L treatment of patients with advanced NSCLC. PD-L1 score was defined as the proportion of tumor cells stained by the assay, and analysis was conducted for patients whose tumors had PD-L1 score 1-49%. Tumor-infiltrating immune cell staining was not considered. OS and PFS were compared between chemo-IO and IO alone via a pooled analysis. Median survival times were estimated using Kaplan-Meier methods. Hazard ratios were estimated using Cox proportional hazards models stratified by trial and adjusted for age, sex, race, ECOG, histology and smoking status. Results: A total of 2108 patients with NSCLC and PD-L1 score 1-49% were identified for this analysis. Baseline characteristics were: 37% aged 65-74 years and 12% aged ≥75; 67% male; 79% white; 65% ECOG ≥ 1; and 85% smokers. Median follow-up was 12.1 months. This pooled analysis showed that patients receiving chemo-IO (N=639) had longer PFS and OS compared to patients treated with IO alone (N=529), with median PFS 7.7 vs 4.2 months (HR 0.60; 95% CI 0.48, 0.76) and median OS 21.4 vs 14.5 months (HR 0.68; 95% CI 0.52, 0.90). All results presented are considered exploratory and hypothesis generating. Conclusions: This exploratory pooled analysis suggests that chemo-IO may improve efficacy outcomes over IO alone in most subgroups of patients with advanced NSCLC with PD-L1 score 1-49%. Patients 75 and over experienced similar outcomes across therapeutic options.[Table: see text]

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Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

Journal of Clinical Medicine ◽

10.3390/jcm10071514 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1514

Author(s):

Hilde Espnes ◽

Jocasta Ball ◽

Maja-Lisa Løchen ◽

Tom Wilsgaard ◽

Inger Njølstad ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Pressure Management ◽

Reference Models ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

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Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study

Cancers ◽

10.3390/cancers13051177 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1177

Author(s):

In Young Choi ◽

Sohyun Chun ◽

Dong Wook Shin ◽

Kyungdo Han ◽

Keun Hye Jeon ◽

...

Keyword(s):

Breast Cancer ◽

Metabolic Syndrome ◽

Proportional Hazards ◽

Screening Program ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

Health Screening Program ◽

Design And Methods

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.

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