scholarly journals Sex Differences in Patients With Occult Cancer After Venous Thromboembolism

2017 ◽  
Vol 24 (3) ◽  
pp. 489-495 ◽  
Author(s):  
Luis Jara-Palomares ◽  
Remedios Otero ◽  
David Jiménez ◽  
Juan Manuel Praena-Fernández ◽  
Agustina Rivas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sex Differences ◽  
Venous Thromboembolism ◽  
Clinical Characteristics ◽  
Treatment Strategies ◽  
Common Cancer ◽  
Occult Cancer ◽  
Increased Risk ◽  
Male Sex ◽  
Increasing Risk

In patients with venous thromboembolism (VTE), male sex has been associated with an increased risk of occult cancer. The influence of sex on clinical characteristics, treatment, cancer sites, and outcome has not been thoroughly investigated yet. We used the Registro Informatizado Enfermedad TromboEmbólica registry to compare the clinical characteristics, treatment strategies, cancer sites, and clinical outcomes in patients with VTE having occult cancer, according to sex. As of June 2014, 5864 patients were recruited, of whom 444 (7.6%; 95% confidence interval: 6.8-8.2) had occult cancer. Of these, 246 (55%) were men. Median time elapsed from VTE to occult cancer was 4 months (interquartile range: 2-8.4), with no sex differences. Women were older, weighed less, and were less likely to have chronic lung disease than men. The most common cancer sites were the lung (n = 63), prostate (n = 42), and colorectal (n = 29) in men and colorectal (n = 38), breast (n = 23), uterine (n = 18), hematologic (n = 17), or pancreas (n = 15) in women. Men were more likely to have lung cancer than women (2.18% vs 0.30%; P < .01) and less likely to have pancreatic cancer (0.17% vs 0.5%; P = .03). Interestingly, breast cancer was more likely found in women aged ≥50 years than in those aged <50 years (0.97% vs 0.14%; P = .03). This study highlights the existence of sex differences in patients with VTE having occult cancer. One in every 2 men had lung, prostate, or colorectal cancer. In women, there is a heterogeneity of cancer sites, increasing risk of breast cancer in those aged >50 years.

scholarly journals Regulatory Role of Sex Hormones in Cardiovascular Calcification

2021 ◽  
Vol 22 (9) ◽  
pp. 4620
Author(s):  
Holly J. Woodward ◽  
Dongxing Zhu ◽  
Patrick W. F. Hadoke ◽  
Victoria E. MacRae
Keyword(s):  
Cardiovascular Disease ◽  
Sex Differences ◽  
Sexual Dimorphism ◽  
Aortic Stenosis ◽  
Sex Hormones ◽  
Sex Hormone ◽  
Increased Risk ◽  
Male Sex ◽  
Primary Male

Sex differences in cardiovascular disease (CVD), including aortic stenosis, atherosclerosis and cardiovascular calcification, are well documented. High levels of testosterone, the primary male sex hormone, are associated with increased risk of cardiovascular calcification, whilst estrogen, the primary female sex hormone, is considered cardioprotective. Current understanding of sexual dimorphism in cardiovascular calcification is still very limited. This review assesses the evidence that the actions of sex hormones influence the development of cardiovascular calcification. We address the current question of whether sex hormones could play a role in the sexual dimorphism seen in cardiovascular calcification, by discussing potential mechanisms of actions of sex hormones and evidence in pre-clinical research. More advanced investigations and understanding of sex hormones in calcification could provide a better translational outcome for those suffering with cardiovascular calcification.

scholarly journals Occult cancer‐related first venous thromboembolism is associated with an increased risk of recurrent venous thromboembolism

2017 ◽  
Vol 15 (7) ◽  
pp. 1361-1367 ◽  
Author(s):  
O. V. Gran ◽  
S. K. Brækkan ◽  
B. Paulsen ◽  
H. Skille ◽  
F. R. Rosendaal ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Occult Cancer ◽  
Increased Risk ◽  
Recurrent Venous Thromboembolism

Breast cancer in women aged 80 years and older: Clinical characteristics and treatment patterns according to biologic subtype.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12594-e12594
Author(s):  
Stephanie M Wong ◽  
Jean-Francois Boileau ◽  
Mariam Rana ◽  
Thierry Muanza ◽  
Richard G. Margolese ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Women ◽  
Clinical Characteristics ◽  
Triple Negative ◽  
Early Stage ◽  
Local Therapy ◽  
Adjuvant Radiation ◽  
Her2 Breast Cancer ◽  
Increased Risk ◽  
Biologic Subtype

e12594 Background: Older age is associated with poorer breast cancer-specific survival (BCSS) outcomes, despite a higher prevalence of biologically favorable disease. We sought to evaluate differences in the clinical characteristics and management of older women according to biologic subtype of breast cancer. Methods: The Surveillance, Epidemiology, and End Results (SEER) treatment database was queried to identify all women aged 80 years or older with a first diagnosis of invasive breast cancer between 2010 and 2016. Patients were subgrouped according to biologic subtype and clinical and treatment-related variables were compared. Multivariable logistic regression was then performed to determine factors independently associated with receipt of breast-conserving surgery (BCS) and adjuvant radiation. Results: Overall, 27,375 women with a median age of 84 (range, 80-108 years) met inclusion criteria. The majority of older women were diagnosed with HR+HER2- breast cancer (78.9%), followed by HER2+ (11.0%) and triple-negative breast cancer (TNBC) (10.0%). In women with stage I-III disease, non-operative management was employed in 13.4% of HR+HER2- patients, compared to 16.7% of HER2+ patients and 11.0% of TNBC (p < 0.001). In those undergoing surgery, BCS was most common in HR+HER2- patients (80.9%), compared to HER2+ (68.9%) and TNBC (67.8%; p < 0.001). Axillary surgery was performed in 74.0% of early stage patients with HR+HER2- disease, compared to patients with HER2+ (77.8%) and TNBC (79.3%; p < 0.001). In adjusted analyses controlling for stage and clinical variables, women aged 80 years or older with HER2+ breast cancer and TNBC had a lower likelihood of BCS (ORHER2+ 0.72, 95% CI 0.65-0.80; ORTNBC 0.72, 95% CI 0.65-0.81), and an increased likelihood of adjuvant radiation (ORHER2+ 1.14, 95% CI 1.02-1.27; ORTNBC 1.40, 95% CI 1.25-1.57). Conclusions: One fifth of women with breast cancer over age 80 are diagnosed with HER2+ and triple-negative subtypes, which are associated with more aggressive local therapy. Further studies are warranted to determine if higher rates of adjuvant radiation optimize local control in older HER2+ and TNBC patients at increased risk for early locoregional recurrences.

scholarly journals Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Chongru Zhao ◽  
Weijie Hu ◽  
Yi Xu ◽  
Dawei Wang ◽  
Yichen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Energy Homeostasis ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Novel Treatment ◽  
Common Cancer ◽  
Prevalence Of Obesity ◽  
Novel Treatment Strategies ◽  
Underlying Mechanisms ◽  
The Impact

Obesity is defined as a chronic disease induced by an imbalance of energy homeostasis. Obesity is a widespread health problem with increasing prevalence worldwide. Breast cancer (BC) has already been the most common cancer and one of the leading causes of cancer death in women worldwide. Nowadays, the impact of the rising prevalence of obesity has been recognized as a nonnegligible issue for BC development, outcome, and management. Adipokines, insulin and insulin-like growth factor, sex hormone and the chronic inflammation state play critical roles in the vicious crosstalk between obesity and BC. Furthermore, obesity can affect the efficacy and side effects of multiple therapies such as surgery, radiotherapy, chemotherapy, endocrine therapy, immunotherapy and weight management of BC. In this review, we focus on the current landscape of the mechanisms of obesity in fueling BC and the impact of obesity on diverse therapeutic interventions. An in-depth exploration of the underlying mechanisms linking obesity and BC will improve the efficiency of the existing treatments and even provide novel treatment strategies for BC treatment.

scholarly journals Endocrine therapy use and the risk of cardiovascular disease in postmenopausal breast cancer survivors: two cohort studies in the UK and US

2019 ◽  
Author(s):  
Anthony Matthews ◽  
Sharon Peacock Hinton ◽  
Susannah Stanway ◽  
Alexander R Lyon ◽  
Liam Smeeth ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Venous Thromboembolism ◽  
Aromatase Inhibitor ◽  
Incidence Rate ◽  
Aromatase Inhibitors ◽  
Cardiovascular Outcomes ◽  
Increased Risk ◽  
The Us ◽  
Venous Thromboembolic ◽  
The Uk

ABSTRACTObjectiveExamine the effect of tamoxifen and aromatase inhibitors on 12 clinically relevant individual cardiovascular outcomes in postmenopausal female breast cancer survivors using large-scale datasets from the UK and US.DesignTwo prospective cohort studiesSettingPopulation-based using data from the UK Clinical Practice Datalink linked with Hospital Episode Statistics (2002-2016), and the US Surveillance, Epidemiology and End Results-Medicare database (2008-2013).Participants10005 and 22027 postmenopausal women with breast cancer in the UK and US respectively.ExposuresAromatase inhibitor compared with tamoxifen use; the US cohort additionally included a comparison with an “unexposed” group of women with oestrogen or progesterone receptor positive breast cancer but no endocrine therapy use.Outcomes12 clinically relevant individual cardiovascular outcomes (and two composite coronary and venous thromboembolic outcomes)ResultsIn both the UK and the US, there was evidence of an increased risk of coronary artery disease in aromatase inhibitor compared with tamoxifen users (UK incidence rate: 10.18 vs 6.87 per 1000 person-years, HR: 1.29, 0.94-1.76; US incidence rate: 35.26 vs 26.95 per 1000 person-years, HR: 1.29, 1.06-1.55), but the US data showed no increase in risk compared with the unexposed group (incidence rate for tamoxifen vs unexposed: 26.95 vs 38.70 per 1000 person-years, HR: 0.74, 0.60-0.92; incidence rate for aromatase inhibitors vs unexposed: 35.26 vs 28.70, HR: 0.96, 0.83-1.10). Similar patterns were seen for other cardiovascular outcomes such as arrhythmia, heart failure, and valvular heart disease. As expected, there were more venous thromboembolic events in tamoxifen users compared with both aromatase inhibitor users and those unexposed. There was a high degree of consistency between results in the two countries.ConclusionsIncreased risks of several cardiovascular diseases among aromatase inhibitor compared with tamoxifen users appeared to be driven by protective effects of tamoxifen, rather than toxic effects of aromatase inhibitors. We also confirmed the known increased risk of venous thromboembolic events in tamoxifen users.WHAT THIS PAPER ADDSWhat is already known on this topicIt is known that tamoxifen use increases venous thromboembolism risk, but evidence for other cardiovascular outcomes is less clear.Patterns of results are suggestive of a lower risk of coronary heart disease outcomes with tamoxifen compared to both aromatase inhibitor use and no tamoxifen or placebo, but cardiovascular events are often a secondary consideration and inconsistently reported in trials, and most observational studies use composite cardiovascular definitions, ignoring potentially differential effects on specific cardiovascular outcomes.What this study addsAmong postmenopausal women with breast cancer, we found an increased risk of several cardiovascular diseases in aromatase inhibitor compared with tamoxifen users across two countries, which appeared to be driven by protective effects of tamoxifen, rather than toxic effects of aromatase inhibitors. We also found the known increased venous thromboembolism risk in tamoxifen users.There was no evidence that aromatase inhibitors or tamoxifen increases cardiovascular disease risk, other than the known increased venous thromboembolism risk with tamoxifen use. However, there was an apparent protective effect of tamoxifen on other cardiovascular outcomes.

scholarly journals Clinical characteristics and outcomes of adult patients admitted with COVID-19 in East London: a retrospective cohort analysis

2020 ◽  
Author(s):  
Daryl Oswald Cheng ◽  
Claire Jacqueline Calderwood ◽  
Erik Wilhelm Skyllberg ◽  
Adam Denis Jeremy Ainley
Keyword(s):  
Clinical Characteristics ◽  
Clinical Course ◽  
Cohort Analysis ◽  
Short Term ◽  
Asian Ethnicity ◽  
Persistent Symptoms ◽  
Risk Of Death ◽  
Increased Risk ◽  
Male Sex

AbstractBackgroundDescriptions of clinical characteristics of patients hospitalised with coronavirus disease 2019 (COVID-19), their clinical course and short-term in- and outpatient outcomes in deprived urban populations in the United Kingdom are still relatively sparse. We describe the epidemiology, clinical course, experience of non-invasive ventilation and intensive care, mortality and short-term sequalae of patients admitted to two large District General Hospitals across a large East London NHS Trust during the first wave of the pandemic.MethodsA retrospective analysis was carried out on a cohort of 1,946 patients with a clinical or laboratory diagnosis of COVID-19, including descriptive statistics and survival analysis. A more detailed analysis was undertaken of a subset of patients admitted across three Respiratory Units in the trust.ResultsIncreasing age, male sex and Asian ethnicity were associated with worse outcomes. Increasing severity of chest X-ray abnormalities trended with mortality. Radiological changes persisted in over 50% of cases at early follow up (6 weeks). Ongoing symptoms including hair loss, memory impairment, breathlessness, cough and fatigue were reported in 67% of survivors, with 42% of patients unable to return to work due to ongoing symptoms.ConclusionsUnderstanding the acute clinical features, course of illness and outcomes of COVID-19 will be vital in preparing for further peaks of the pandemic. Our initial follow up data suggest there are ongoing sequalae of COVID-19 including persistent symptoms and radiological abnormalities. Further data, including longer term follow up data, are necessary to improve our understanding of this novel pathogen and associated disease.Section 1: What is already known on this topicPrevious studies have reported that increasing age, male sex, Black and Asian ethnicity increased risk of death for patients admitted to hospital with coronavirus disease 2019 (COVID-19). There is little published literature regarding the follow up of patients with COVID-19.Section 2: What this study addsOur study is one of the first with follow up data for patients admitted to hospital with COVID-19. We show that radiological abnormality persisted at 6 weeks in over 50% of patients, as well as significantly increased breathlessness in patients without baseline dyspnoea. Our study confirms that increasing age, male sex and Asian ethnicity increased risk of death for patients, but also in an ethnically and socioeconomically diverse population in East London.

Clinical characteristics and outcomes of patients with venous thromboembolism according to diagnosis on weekends versus weekdays: from the COMMAND VTE Registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Yamashita ◽  
T Morimoto ◽  
T Makiyama ◽  
K Ono ◽  
T Kimura
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Clinical Outcomes ◽  
Clinical Characteristics ◽  
Anticoagulation Therapy ◽  
Treatment Strategies ◽  
Funding Source ◽  
Medical Systems ◽  
Severe Condition ◽  
Entire Cohort

Abstract Background/Introduction The medical systems of hospitals often differs between on weekends and weekdays. These differences could lead different clinical outcomes for patients with acute medical conditions that require complex treatment strategies. However, the effect of the time of diagnosis on clinical outcomes in patients with acute venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), is still controversial. Purpose We sought to evaluate the clinical characteristics and outcomes of patients with VTE comparing on weekends and weekdays in a large observational database of VTE in Japan. Methods The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE objectively confirmed by imaging examination or by autopsy among 29 centers in Japan between January 2010 and August 2014. In the current analysis, diagnosis on weekends was defined as diagnosis during the period from 00:00 hours on Saturday to 24:00 on Sunday. All other times were defined as weekdays. We divided the entire cohort into 2 groups; diagnosis on weekends and diagnosis on weekdays groups, and we compared the clinical characteristics, management strategies and 30-day outcomes between the 2 groups. Results The current study population consisted of 337 patients diagnosed on weekends and 2690 patients diagnosed on weekdays. The median days from onset to diagnosis were shorter in the patients diagnosed on weekends than in those diagnosed on weekdays (2 days vs. 4 days, P&lt;0.001). The patients diagnosed on weekends presented with PE more frequently (72% vs. 55%, P&lt;0.001), and they showed more severe condition for PE with a higher simplified pulmonary embolism severity index score. The vast majority of PE patients were diagnosed by contrast-enhanced computed tomography in both groups (97% vs. 97%, P=0.67). The patients diagnosed on weekends more often received initial parenteral anticoagulation therapy and thrombolysis than those diagnosed on weekdays. The cumulative 30-day incidence of all-cause death was not significantly different between the 2 groups among PE patients (diagnosis on weekends: 6.2% vs. diagnosis on weekdays: 6.5%, P=0.87), as well as among DVT patients (0.0% vs. 1.5%, P=0.24) (Figure). After adjusting the confounders, the risk of diagnosis on weekends relative to diagnosis on weekdays for all-cause death among PE patients was still insignificant (adjusted HR: 0.76; 95% CI: 0.42–1.28). The most frequent cause of deaths was fatal PE in both groups among PE patients. The risks for recurrent VTE and major bleeding at 30 days were not significantly different between the 2 groups among PE patients nor DVT patients. Conclusions The VTE patients diagnosed on weekends presented with PE more frequently, and they showed more severe condition for PE, although the risks for short-term mortality were not significantly different between patients diagnosed on weekends and weekdays. Kaplan-Meier curves for all-cause death Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

Race and Cancer-Associated Venous Thromboembolism in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3551-3551
Author(s):  
Daniel Douce ◽  
Nels Olson ◽  
Mary Cushman ◽  
Pamela L Lutsey ◽  
Suzanne Judd ◽  
...  
Keyword(s):  
United States ◽  
Venous Thromboembolism ◽  
Confidence Interval ◽  
Trauma Surgery ◽  
The United States ◽  
Southeastern Us ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Male Sex ◽  
Blacks And Whites

Abstract Introduction: Venous thromboembolism (VTE) is classified as provoked (associated with surgery, hospitalization, trauma, or cancer) and unprovoked events. Whether provoked, unprovoked or cancer-associated VTE differs by age, sex, race, or region in the United States is poorly understood. Methods: VTE events were ascertained in 30,183 individuals in the REGARDS cohort enrolled between 2003-2007 in the contiguous United States. Participants were enrolled in their homes, with a goal of 50% of the cohort being black, female, and living in the southeastern US. VTE events were identified by telephone interviews, review of hospitalizations and deaths and validated by physician review of medical records. Cancer-associated VTE (CA-VTE) was defined as a VTE associated with active cancer or chemotherapy in the last 90 days. Non-cancer, provoked VTE was defined as a VTE that was preceded within 90 days by major trauma, surgery, or hospitalization. Unprovoked VTE was defined as having none of the above risk factors. The associations of age, sex, race and region with cancer-associated, provoked, and unprovoked VTE were analyzed by chi square analyses and Cox proportional hazard ratios that were adjusted for age, sex, race, region and obesity. Results: Overall, 332 VTE events occurred over a mean of 4.7 years follow up. Of these, 163 events (49.1%) were provoked, 47 (14.2%) were CA-VTE. The proportion of unprovoked to provoked VTE did not differ by age (120 to 104 in those older than 65, 49 to 59 for those under 65, p=0.16) sex (98 to 90 in men, 71 to 73 in women, p=0.61), race (61 to 62 in blacks, 108 to 101 in whites, p=0.71) or region (89 to 88 in the Southeast, 80 to 75 for the rest of the country p=0.81); however CA-VTE was significantly less common in blacks (11 of 123, 8.9%) than whites (36 of 209, 17.2%) (p=0.04). While the overall risk of VTE was similar in blacks and whites, blacks had a lower risk of CA-VTE than whites (Hazard Ratio (HR) 0.38, 95% Confidence Interval (CI) 0.18-0.77). Increased age and male sex were associated with an increased risk for all-cause VTE and unprovoked VTE with a trend for male sex and increased risk for provoked VTE (Table). However, men had no increased risk of CA-VTE compared to women (0.85 95% CI 0.46-1.55). Discussion: The proportion of provoked versus unprovoked VTE events did not differ by age, sex, race or region in REGARDS, though blacks had a lower proportion of CA-VTE than whites. Men overall had a higher risk of VTE than women, but there was no increased risk for CA-VTE in men. Blacks and whites had a similar risk of VTE overall, however blacks had a lower incidence of CA-VTE than whites. Possible reasons for our findings include shorter survival after a diagnosis of cancer, different cancer types or treatments, or differential ascertainment of VTE by race or sex. These findings highlight the need to understand how sex and race impact VTE incidence so we can best prevent VTE in everyone. Table. Hazard Ratios for different VTE subtypes by Age, Sex, and Race (95% Confidence Interval) All VTE Unprovoked VTE Provoked VTE Cancer-Associated VTE Age (per SD, 9.4 years) 1.61 (1.43-1.80) 1.70 (1.44-1.99) 1.52 (1.29-1.79) 1.48 (1.09-2.02) Male Sex 1.42 (1.13-1.78) 1.52 (1.11-2.09) 1.32 (0.96-1.82) 0.85 (0.47-1.55) Black versus White Race 0.90 (0.71-1.13) 0.84 (0.61-1.16) 0.96 (0.69-1.34) 0.38 (0.18-0.77) Disclosures No relevant conflicts of interest to declare.

scholarly journals Targeted Therapies in HER2-Positive Breast Cancer - a Systematic Review

Breast Care ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 173-178 ◽  
Author(s):  
Amelie Schramm ◽  
Nikolaus De Gregorio ◽  
Peter Widschwendter ◽  
Visnja Fink ◽  
Jens Huober
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Increased Risk ◽  
Positive Breast Cancer

About 20% of all breast cancer patients have a human epidermal growth factor receptor 2 (HER2)-positive breast tumor. This entity underwent an impressive change in prognosis, with notable improvement of progression-free survival and overall survival. Due to more aggressive tumors and no specific therapy, HER2 overexpression was historically seen as a negative prognostic marker, with worse prognosis and increased risk of recurrent disease. Trastuzumab, the first anti-HER2 antibody, revolutionized the systemic therapy options in HER2-positive breast cancer and initiated several targeted therapies and more personalized treatment strategies. Over the years, multiple HER2-targeting drugs stepped into clinical practice, for the curative as well as the metastatic situation. This review summarizes the targeted treatment options in HER2-positive breast cancer and their current impact in the clinical routine. Results of the most outstanding trials in HER2-targeted therapies and important ongoing trials are subsequently described for an up-to-date overview.

scholarly journals Fasting C-Peptide Levels and Death Resulting From All Causes and Breast Cancer: The Health, Eating, Activity, and Lifestyle Study

2011 ◽  
Vol 29 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Melinda L. Irwin ◽  
Catherine Duggan ◽  
Ching-Yun Wang ◽  
Ashley Wilder Smith ◽  
Anne McTiernan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Type 2 Diabetes ◽  
Cox Regression ◽  
Treatment Strategies ◽  
Breast Cancer Diagnosis ◽  
C Peptide ◽  
Risk Of Death ◽  
Increased Risk ◽  
Health Eating

Purpose To examine the association between serum C-peptide, a marker of insulin secretion, measured 3 years after a breast cancer diagnosis, and death resulting from all causes and breast cancer. Patients and Methods This was a prospective, observational study of 604 women enrolled onto the Health, Eating, Activity, and Lifestyle (HEAL) Study who were diagnosed with local or regional breast cancer between 1995 and 1998 and observed until death or December 31, 2006, whichever came first. The hazard ratio (HR) for all deaths and deaths owing to breast cancer and 95% CIs for the HR were estimated using multivariable stratified Cox regression analyses. Results Among women without type 2 diabetes, fasting C-peptide levels were associated with an increased risk of death resulting from all causes and from breast cancer. A 1-ng/mL increase in C-peptide was associated with a 31% increased risk of any death (HR = 1.31; 95% CI, 1.06 to 1.63; P = .013) and a 35% increased risk of death as a result of breast cancer (HR = 1.35; 95% CI, 1.02 to 1.87, P = .048). Associations between C-peptide levels and death as a result of breast cancer were stronger in certain subgroups, including women with type 2 diabetes, women with a body mass index less than 25 kg/m2, women diagnosed with a higher stage of disease, and women whose tumors were estrogen receptor positive. Conclusion Treatment strategies to reduce C-peptide levels in patients with breast cancer, including dietary-induced weight loss, physical activity, and/or use of insulin-lowering medications, should be explored.

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