c-peptide and Breast-Neoplasms

A case of hypoglycemic coma caused by a giant borderline phyllodes tumor of the breast has been described. The patient, a 63-year-old woman, was admitted with recurrent unconsciousness. She had a giant breast tumor with decreased blood glucose, insulin, and C-peptide. The patient's hypoglycemia resolved rapidly after resection of the breast tumor. Pathological examination indicated a borderline phyllodes tumor of the breast, and immunohistochemistry suggested high expression of insulin-like growth factor-2 (IGF-2) in the tumor tissue. A literature review is also included to summarize the clinical characteristics of such patients and to serve as a unique resource for clinical diagnosis and treatment of similar cases.

Topics: Breast Neoplasms; C-Peptide; Female; Humans; Hypoglycemia; Insulin; Middle Aged; Phyllodes Tumor

This study was undertaken to evaluate the association between components defining insulin resistance and breast cancer in women.. We conducted a systematic review of four databases (PubMed-Medline, EMBASE, Web of Science, and Scopus) for observational studies evaluating components defining insulin resistance in women with and without breast cancer. A meta-analysis of the association between insulin resistance components and breast cancer was performed using random effects models.. Twenty-two studies (n = 33,405) were selected. Fasting insulin levels were not different between women with and without breast cancer (standardized mean difference, SMD -0.03, 95%CI -0.32 to 0.27; p = 0.9). Similarly, non-fasting/fasting C-peptide levels were not different between the two groups (mean difference, MD 0.07, -0.21 to 0.34; p = 0.6). Using individual odds ratios (ORs) adjusted at least for age, there was no higher risk of breast cancer when upper quartiles were compared with the lowest quartile (Q1) of fasting insulin levels (OR Q2 vs. Q1 0.96, 0.71 to 1.28; OR Q3 vs. Q1 1.22, 0.91 to 1.64; OR Q4 vs. Q1 0.98, 0.70 to 1.38). Likewise, there were no differences for quartiles of non-fasting/fasting C-peptide levels (OR Q2 vs. Q1 1.12, 0.91 to 1.37; OR Q3 vs. Q1 1.20, 0.91 to 1.59; OR Q4 vs. Q1 1.40, 1.03 to 1.92). Homeostatic model assessment (HOMA-IR) levels in breast cancer patients were significantly higher than in people without breast cancer (MD 0.22, 0.13 to 0.31, p<0.00001).. Higher levels of fasting insulin or non-fasting/fasting C-peptide are not associated with breast cancer in women. HOMA-IR levels are slightly higher in women with breast cancer.

Topics: Breast Neoplasms; C-Peptide; Fasting; Female; Humans; Insulin; Insulin Resistance; Odds Ratio; Publication Bias

Chronic hyperinsulinemia may play a role in breast cancer etiology. We performed a meta-analysis examining whether serum concentrations of insulin and C-peptide are associated with increased breast cancer risk.. We restricted our analyses to prospective studies. After a systematic literature search, we computed summary relative risks (SRRs) and 95 % confidence intervals (95 % CIs) using random effect models applied to the relative risk associated with the highest versus lowest quantile of serum concentrations. We also graphically examined results in order to identify whether dose-response relationships were present.. Six articles including 1,890 cases were retrieved for serum insulin levels and five for serum C-peptide levels including 1,759 cases. SRR and 95 % CI were 1.08 (0.66-1.78) for insulin and 1.04 (0.77-1.41) for C-peptide. Heterogeneity of results between studies was high for insulin and inexistent for C-peptide. Restricting the analysis to women diagnosed with breast cancer before or after menopause did not alter results. In insulin studies, SRR computed from relative risks not adjusted for body mass index (and other risk factors) was 1.22 (0.91-1.63). The SRR fell to 1.02 (0.53-1.97) in studies that adjusted for body mass index and other factors. Similar drops occurred in C-peptide studies, from 1.11 (0.87-1.41) to 1.06 (0.70-1.61). No consistent dose-response relationship was apparent in either pre- or post-menopausal cancers.. Our meta-analysis of observational studies found no evidence of an association between serum insulin or C-peptide concentrations and breast cancer risk. Increased risk found by some studies may have been due to inadequate control for adiposity.

Topics: Breast Neoplasms; C-Peptide; Female; Humans; Insulin; Risk Assessment

Obesity-associated breast cancer recurrence is mechanistically linked with elevated insulin levels and insulin resistance. Exercise and weight loss are associated with decreased breast cancer recurrence, which may be mediated through reduced insulin levels and improved insulin sensitivity. This is a secondary analysis of the WISER Survivor clinical trial examining the relative effect of exercise, weight loss and combined exercise and weight loss interventions on insulin and insulin resistance. The weight loss and combined intervention groups showed significant reductions in levels of: insulin, C-peptide, homeostatic model assessment 2 (HOMA2) insulin resistance (IR), and HOMA2 beta-cell function (β) compared to the control group. Independent of intervention group, weight loss of ≥10% was associated with decreased levels of insulin, C-peptide, and HOMA2-IR compared to 0-5% weight loss. Further, the combination of exercise and weight loss was particularly important for breast cancer survivors with clinically abnormal levels of C-peptide.

Topics: Blood Glucose; Breast Neoplasms; C-Peptide; Cancer Survivors; Exercise Therapy; Female; Humans; Insulin; Insulin Resistance; Middle Aged; Neoplasm Recurrence, Local; Weight Reduction Programs

Somatostatin analogs act directly on breast cancer cells and indirectly on insulin and insulin-like growth factor 1 (IGF-1) levels. This trial was undertaken to assess whether octreotide would lower insulin and IGF-1 levels and reduce risk of breast cancer recurrence.. The NCIC CTG MA.14 (NCIC Clinical Trials Group MA.14) trial randomly assigned postmenopausal women to 5 years of tamoxifen 20 mg daily (TAM) or TAM plus 2 years of octreotide 90 mg depot intramuscular injections monthly (TAM-OCT) as adjuvant therapy. The primary end point was event-free survival (EFS). Secondary end points were relapse-free survival (RFS), overall survival (OS), toxicity, and effects of treatment on IGF physiology.. Among 667 women with a median follow-up of 7.9 years, 220 events occurred-108 with TAM-OCT and 112 with TAM. Adjusted hazard ratios (HRs; TAM-OCT to TAM) were 0.93 for EFS (95% CI, 0.71 to 1.22; P = .62), 0.84 for RFS (95% CI, 0.59 to 1.18; P = .31), and 0.97 for OS (95% CI, 0.69 to 1.37; P = .86). Among patients with normal baseline gallbladder imaging, cholecystectomy was required in 23.0% of those receiving TAM-OCT but in only 1.4% of those receiving TAM (P < .001). At 4 months, TAM-OCT had significantly (P < .001) lowered IGF-1, IGF binding protein 3, and C-peptide levels. Older age (P = .02), tumor size (P = .001), nodal status (P = .01), high C-peptide levels (P < .001), and higher body mass index (BMI) in models excluding C-peptide (P < .001) were associated with poorer EFS in multivariate analysis.. Octreotide-related changes in circulating IGF-1 and C-peptide levels were statistically significant. Octreotide did not add significant clinical benefit. High C-peptide levels (surrogate for insulin secretion rate) and high BMI were associated with poor outcome.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; C-Peptide; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Insulin; Insulin-Like Growth Factor I; Middle Aged; Octreotide; Postmenopause; Quality of Life; Tamoxifen; Treatment Outcome; Vitamin D

C-peptide is usually considered as a marker of insulin secretion and has no physiological function. This study aimed to assess the association between serum C-peptide level as independent risk factor and breast cancer and explored the possible underlying mechanisms. This was a population-based cohort study. All the data was collected according to a standard protocol. The C-peptide and insulin-like growth factor binding proteins-3(IGFBP-3) concentrations were measured in blood. The breast cancer deaths were confirmed by National Death Index records. Cox proportional hazard regression analysis was conducted to determine the hazard ratio of serum C-peptide level for breast cancer deaths. Analysis of covariance was used to assess the association between serum C-peptide and IGFBP-3 level, and the linear trend was tested by using a linear model. A total of 8,373 women 17 years of age or older were included in the study, and 57 breast cancer deaths were observed over the study period. The result of survival analysis showed that breast cancer deaths increased with increasing levels of serum C-peptide. The hazard ratio was 1.69 (95% confidence interval, 1.17-2.45). The levels of circulating IGFBP-3 were positively associated with changes in serum C-peptide levels and showed a strong linear trend in the covariance analysis. Serum C-peptide level was associated with increased risk of breast cancer death. Our results suggest that the increased risk of breast cancer death can be via a pathway that serum C-peptide level positive associated with the change in serum IGFBP-3 level.

Topics: Adult; Aged; Breast Neoplasms; C-Peptide; Cohort Studies; Female; Health Surveys; Humans; Insulin-Like Growth Factor Binding Protein 3; Middle Aged; Proportional Hazards Models; Risk Factors; Survival Analysis

C-peptide, insulin, leptin, and other metabolic hormones are assumed to play roles in breast cancer development; though, results are inconsistent. In this prospective case-control study nested within the Mano a Mano Cohort Study, we assessed the risk of breast cancer with regard to plasma levels of c-peptide, gastric inhibitory polypeptide, insulin, leptin, monocyte chemoattractant protein-1, pancreatic polypeptide, and peptide YY. Among women followed for a median of 8.5 years, 109 breast cancer cases were identified and frequency-matched to 327 controls at a ratio of 1:3. Overall, only c-peptide was observed significantly associated with breast cancer risk. High c-peptide levels (≥ the median level of controls) were significantly associated with increased breast cancer risk (odds ratio [OR] = 1.39, 95% confidence interval [CI]: 1.01, 2.44). In an analysis of participants stratified by age, the significant association between c-peptide levels and breast cancer risk was evident in only women age ≥51 years (OR = 1.53, 95% CI: 1.02, 3.27). Among women age <51 years, high leptin levels were significantly associated with decreased breast cancer risk (OR = 0.49, 95% CI: 0.24, 0.82). Our findings suggest that selected metabolic hormones are associated with breast cancer development in Mexican American women.

Topics: Age Factors; Breast Neoplasms; C-Peptide; Case-Control Studies; Chemokine CCL2; Female; Gastric Inhibitory Polypeptide; Humans; Insulin; Leptin; Mexican Americans; Pancreatic Polypeptide; Peptide YY; Prospective Studies; Risk Factors; United States; Up-Regulation

Type-2 diabetes mellitus (T2DM) and breast cancer (BC) share common cytokine signaling changes resultant from adipose tissue dysfunction. This modified adipokine signaling was shown to be directly associated with changes in the body mass index (BMI) and diet and it is expected to also be influenced by T2DM pharmacotherapy. We evaluated the relationship between pre-existing diabetes treatment, circulating adipokine levels at cancer diagnosis, and long-term outcomes.. Insulin use is associated with elevated leptin, CRP, TNFα, and lower C-peptide and also linked to poor BC outcomes. More research is needed to verify these findings; however, we are among the first to correlate pharmacotherapy use, measures of adipose tissue dysfunction and cancer outcomes.

Topics: Adult; Aged; Breast Neoplasms; C-Peptide; C-Reactive Protein; Cytokines; Diabetes Mellitus, Type 2; Disease-Free Survival; Female; Humans; Insulin; Leptin; Middle Aged; Survival Rate

Weight gain in breast cancer patients during treatment is prevalent; the metabolic implications of this weight gain are poorly understood. We aimed to characterize glucose metabolism in breast cancer patients near the initiation of chemotherapy.. Stage I-II breast cancer patients (n = 8) were evaluated near the initiation of chemotherapy and compared with a group of age- and body mass index-matched, as well as a group of young healthy, non-malignant females. Fasting blood samples (analyzed for lipids and cytokines) were taken and an oral glucose tolerance test was performed. Body composition, waist circumference, diet, cardiovascular fitness and muscle strength were evaluated.. Breast cancer patients were abdominally obese (mean ± SD: 94.6 ± 14.0 cm), overweight (28.8 ± 6.0 kg/m(2)) and dyslipidemic (triacylglycerides: 1.84 ± 1.17 mM; high-density lipoprotein cholesterol: 1.08 ± 0.23 mM). Compared to non-malignant matched females, fasting glucose and insulin concentrations were similar but fasting c-peptide was greater in patients (2.6 ± 1.2 ng/mL vs. 1.9 ± 0.8 ng/mL, p = 0.005). Glucose was elevated to a greater extent in patients during the oral glucose tolerance test compared with all non-malignant females. During the glucose tolerance test, c-peptide, but not insulin, remained elevated in patients compared with all non-malignant females. No differences in body composition, serum cytokines, nutrition or exercise capacity between patients and matched, non-malignant females emerged.. Breast cancer patients present with unhealthy metabolic features early in the disease trajectory. Future investigations need to examine the underlying mechanisms and the potential longitudinal changes following chemotherapy.

Topics: Adolescent; Adult; Blood Glucose; Body Composition; Body Mass Index; Breast Neoplasms; C-Peptide; Cholesterol, HDL; Cytokines; Diet Records; Dyslipidemias; Energy Intake; Energy Metabolism; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Middle Aged; Motor Activity; Muscle Strength; Obesity; Waist Circumference; Weight Gain; Young Adult

We examined whether waist circumference (WC) and waist-to-hip ratio (WHR) after breast cancer diagnosis are associated with all-cause or breast cancer-specific mortality and explored potential biological pathways mediating these relationships. Our analysis included 621 women diagnosed with local or regional breast cancer who participated in the Health, Eating, Activity, and Lifestyle study. At 30 (±4) months postdiagnosis, trained staff measured participants' waist and hip circumferences and obtained fasting serum samples for biomarker assays for assays of insulin, glucose, C-peptide, insulin growth factor-1 and binding protein-3, C-reactive protein (CRP), and adiponectin. We estimated multivariate hazard ratios (HR) and 95 % confidence intervals (CI) for death over ~9.5 years of follow-up. After adjustment for measured body mass index, treatment, comorbidities, race/ethnicity, diet quality, and postdiagnosis physical activity, WC was positively associated with all-cause mortality (HRq4:q1: 2.99, 95 % CI 1.14, 7.86) but its positive association with breast cancer-specific mortality was not statistically significant (HRq4:q1: 2.69, 95 % CI 0.69, 12.01). WHR was positively associated with all-cause mortality (HRq4:q1: 2.10, 95 % CI 1.08, 4.05) and breast cancer-specific mortality (HRq4:q1: 4.02, 95 % CI 1.31, 12.31). After adjustment for homeostatic model assessment (HOMA) score and C-reactive protein, risk estimates were attenuated and not statistically significant. In this diverse breast cancer survivor cohort, postdiagnosis WC and WHR were associated with all-cause mortality. Insulin resistance and inflammation may mediate the effects of central adiposity on mortality among breast cancer patients.

Topics: Adiponectin; Adiposity; Aged; Blood Glucose; Breast Neoplasms; C-Peptide; Feeding Behavior; Female; Humans; Insulin; Insulin Resistance; Middle Aged; Motor Activity; Obesity, Abdominal; Waist Circumference; Waist-Hip Ratio

Insulin may promote breast cancer directly by stimulating the insulin receptor or indirectly by increasing the plasma concentration of active sex hormones. The association between insulin and breast density, a strong breast cancer risk factor, has not been thoroughly studied. We measured associations between c-peptide (a molar marker of insulin secretion), breast cancer risk, and breast density measurements in case-control studies nested within the Nurses' Health Study and Nurses' Health Study II cohorts.. Breast cancer associations were estimated with multivariate logistic regression models and then pooled across cohorts (total n = 1,084 cases and 1,785 controls). Mammographic density associations (percent dense area, dense area, and nondense area) were estimated as the difference in least-square means of the density parameters between quartiles of c-peptide concentration in all breast cancer controls with available screening mammography films (n = 1,469).. After adjustment for adiposity, c-peptide was not associated with any measure of breast density. However, c-peptide was associated with an approximately 50% increased risk of invasive breast cancer [top vs. bottom quartile, adjusted OR = 1.5, 95% confidence interval (CI), 1.1-2.0] that was robust to adjustment for plasma-free estradiol and sex hormone-binding globulin. The association was stronger for ER-negative disease (adjusted OR = 2.0; 95% CI, 1.2-3.6).. Our data suggest a positive association between hyperinsulinemia and breast cancer risk that occurs through nonestrogenic mechanisms, and that is not mediated by breast density.. Primary prevention of breast cancer in women with hyperinsulinemia may be possible by targeting insulin signaling pathways.

Topics: Breast Density; Breast Neoplasms; C-Peptide; Cohort Studies; Female; Humans; Logistic Models; Mammary Glands, Human; Middle Aged; Radiography; Risk Factors

Two groups of breast cancer patients (53±2 years) in clinical remission receiving no specific therapy were examined: group 1, with BRCA1 gene mutations (N=11) and group 2, without mutations of this kind (N=11). The two groups did not differ by insulinemia and glycemia, insulin resistance index, blood levels of thyrotropic hormone, sex hormone-binding globulin, insulin-like growth factor-1, triglycerides, or lipoproteins. In group 1, blood estradiol level was higher. Intensive glucose-induced generation of reactive oxygen species in these patients was associated with a decrease of cholesterolemia, of the C-peptide/insulin proportion, and a trend to higher urinary excretion of 4-hydroxyestrone, one of the most genotoxic catecholestrogens. BRCA1 gene mutations in breast cancer patients were associated with signs of estrogenization and a pro-genotoxic shift in the estrogen and glucose system, which could modulate the disease course and requires correction.

Topics: Blood Glucose; BRCA1 Protein; Breast Neoplasms; C-Peptide; Endocrine System; Estradiol; Female; Humans; Hydroxyestrones; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Lipoproteins; Middle Aged; Mutation; Reactive Oxygen Species; Sex Hormone-Binding Globulin; Thyrotropin; Triglycerides

We report an exceptional case of non-islet cell tumor-induced hypoglycemia (NICTH) secondary to "Big"-IGF-2 oversecretion due to a giant phyllode tumor of the breast.. A 49-year-old woman was admitted in emergency for brutal neurologic defect revealing severe hypoglycemia. Several similar episodes were observed throughout hospitalization, requiring continue perfusion of hypertonic glucose solution. Beside these metabolic disorders, we observed a giant and hard tumor of the left breast (about 30cm in diameter).. Supplementary blood analysis revealed serum levels of C-peptide and insulin suppressed during hypoglycemia, excluding the possibility of either endogenous or exogenous hyperinsulinism. Low plasma levels of GH and IGF-1 were found, suggesting a negative feedback loop on somatotroph axis function. Therefore, the hypothesis of an insulinomimetic compound released by tumor cells was evoked because of abnormal presence of high-weight and immature form of IGF-2 (called "Big"-IGF-2) in the serum identified by western immunoblot analysis. A left mastectomy was performed and completely restored glucose homeostasis and confirmed the paraneoplastic origin of hypoglycemia because of markedly elevated expression of IGF-2 mRNA (qPCR) within the tumor cells. Finally, the anatomopathology analysis diagnosed a mesenchymatous tumor, namely a high-grade phyllode sarcoma of the breast.. Although NICTH due to "Big"-IGF-2 overproduction is a rare phenomenon, mainly observed in case of mesenchymatous tumor, it should be considered in presence of severe hypoglycemia with voluminous tumor and without hyperinsulinism.

Topics: Breast Neoplasms; C-Peptide; Fatal Outcome; Female; Human Growth Hormone; Humans; Hypoglycemia; Insulin; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Mastectomy; Middle Aged; Phyllodes Tumor; Protein Precursors

The study was conducted to assess biochemical profiles in premenopausal and postmenopausal women having breast cancer.. A hospital based case control study was carried out at Manipal Teaching Hospital (MTH), Pokhara, Nepal. The analysed variables were age, metabolic profile including total cholesterol, triglycerides, HDL-C, LDL-C, blood sugar, insulin concentration, C-peptide, HbA1c and selenium. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software.. In premenopausal women, significant differences were noted for total cholesterol (P value <0.001), triglycerides (P value 0.002), HbA1c level (P value <0.001), insulin concentration (P value 0.030), C-peptide concentration (P value 0.001), and selenium (P value <0.001) between cases and controls. Insignificant results were found for HDL-C (P value 0.749), LDL-C (P value 0.933), blood sugar (P value 0.59) and BMI (P value 0.746). Similarly, significant difference in total cholesterol (P value <0.001), triglycerides (P value 0.001), LDL-C (P value <0.001), HDL-C (P value 0.025), blood sugar (P value <0.001), insulin concentration (P value <0.001), c-peptide concentration (P value <0.001), HbA1c level (P value <0.001) and selenium (P value <0.001) were observed for postmenopausal patients and controls.. Assessing metabolic changes and their management may be important for control of breast cancer and increased survival.

Topics: Adult; Aged; Blood Glucose; Breast Neoplasms; C-Peptide; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Female; Glycated Hemoglobin; Humans; Insulin; Middle Aged; Postmenopause; Premenopause; Selenium; Triglycerides

To evaluate the association between self-reported diabetes and the risk of breast cancer (BC) and its interaction with moderate-intensity physical activity in pre- and postmenopausal Mexican women.. A population-based case-control study was conducted using 1,000 incident case subjects and 1,074 control subjects. Blood samples and information on health, diet, physical activity, and anthropometric measurements were obtained.. The association between diabetes and BC risk decreased with increasing tertiles of moderate-intensity physical activity (odds ratio [OR] = 4.9 [95% CI 2.3-10.8]; 3.0 [1.3-6.9]; and 1.0 [0.1-9.2], respectively, for each tertile) (test for interaction = 0.04). Compared with the women in the lowest tertiles, increased risk was observed in those premenopausal women with the highest serum C-peptide, IGF-1, and IGF-1 binding protein 3 levels.. Moderate-intensity physical activity can substantially ameliorate the increased BC risk in diabetic women.

Topics: Breast Neoplasms; C-Peptide; Case-Control Studies; Exercise; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Odds Ratio; Postmenopause; Premenopause

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.. 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.. 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/m(2), women diagnosed with a higher stage of disease, and women whose tumors were estrogen receptor positive.. 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.

Topics: Breast Neoplasms; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Life Style; Middle Aged; Motor Activity; Prognosis; Prospective Studies; Risk Factors

Sex and growth hormones are positively associated with postmenopausal breast cancer risk. However, few studies have evaluated the influence of multiple hormones simultaneously.. We considered the roles of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate and prolactin and, secondarily, insulin-like growth factor 1 (IGF-1) and c-peptide in postmenopausal breast cancer risk among 265 cases and 541 controls in the prospective Nurses' Health Study. We created several hormone scores, including ranking women by the number of hormones above the age- and batch-adjusted geometric mean and weighting hormone values by their individual associations with breast cancer risk.. Women in the top versus bottom quintile of individual estrogen or androgen levels had approximately a doubling of postmenopausal breast cancer risk. Having seven or eight compared to zero hormones above the geometric mean level was associated with total (RR = 2.7, 95% CI = 1.3 to 5.7, P trend < 0.001) and estrogen receptor (ER)-positive (RR = 3.4, 95% CI = 1.3 to 9.4, P trend < 0.001) breast cancer risk. When comparing the top versus bottom quintiles of the score weighted by individual hormone associations, the RR for total breast cancer was 3.0 (95% CI = 1.8 to 5.0, P trend < 0.001) and the RR for ER-positive disease was 3.9 (95% CI = 2.0 to 7.5, P trend < 0.001). The risk further increased when IGF-1 and c-peptide were included in the scores. The results did not change with adjustment for body mass index.. Overall, the results of our study suggest that multiple hormones with high circulating levels substantially increase the risk of breast cancer, particularly ER-positive disease. Additional research should consider the potential impact of developing risk prediction scores that incorporate multiple hormones.

Topics: Adult; Aged; Breast Neoplasms; C-Peptide; Case-Control Studies; Estrogens; Female; Gonadal Steroid Hormones; Humans; Insulin-Like Growth Factor I; Middle Aged; Models, Statistical; Multivariate Analysis; Postmenopause; Prospective Studies; Receptors, Estrogen; Risk Factors; Testosterone

Insulin glargine (Lantus) stimulates growth of MCF-7 cells stronger than human insulin. We investigated if serum from diabetic patients treated with glargine versus human insulin may display a similar effect.. Pairs of serum samples from 31 C-peptide negative type-1 diabetic patients were investigated. In cross-over fashion, 23 patients were treated with glargine plus rapid-acting insulin analogues, and similar doses of human NPH and rapid-acting insulin. For comparison, eight patients were treated with insulin detemir (Levemir) and human NPH. MCF-7 cells were incubated with 10% serum and proliferation was assessed after 72 hours.. Serum containing insulin glargine was 1.11(95% CI 1.05-1.18) fold more mitogenic than human insulin-containing serum (p < 0.005); mitogenicity of serum containing detemir was 0.99(95% CI 0.98-1.02) fold that of human insulin-containing serum.. The serum of diabetic patients was slightly stronger mitogenic when using glargine as compared to human insulin or detemir for treatment.

Topics: Breast Neoplasms; C-Peptide; Cell Line, Tumor; Cells; Chemotactic Factors; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Pilot Projects; Risk Factors

Despite existing epidemiologic data concerning the increased incidence of breast cancer in diabetes type 2, the association between insulin resistance and breast carcinogenesis is not yet well defined. In this cross-sectional study, we examined the homeostatic model assessment values of insulin resistance (HOMA-IR) among 82 patients with malignant breast tumor, 48 subjects with benign breast mass, and 838 healthy Iranian women. One hundred and thirty (n = 130) surgical inpatients of Tehran Central Cancer Institute (Tehran, Iran) were evaluated preoperatively. Healthy subjects were nondiabetic, nonhypertensive women aged 20-77 years from four different locations in Tehran. Age and central obesity-adjusted HOMA-IR values were 3.6 [95% confidence interval (CI), 2.8-4.4], 2.3 (1.7-2.9), and 1.7(1.6-1.8) correspondingly in subjects with malignant breast tumor, those with benign breast mass, and healthy subjects. The interaction effect of age on the association between breast mass (malignant/ benign /no breast mass) with HOMA-IR values was significant [F(54) = 10, P < 0.001, partial eta squared = 0.03]. The interaction of central obesity on this association was also significant [F(54) = 37, P < 0.001, partial eta squared = 0.11]. We conclude that the noted linkage between insulin resistance and breast cancer may indicate an underlying pathology of mammary carcinogenesis.

Topics: Adult; Age Factors; Aged; Blood Glucose; Breast Neoplasms; C-Peptide; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Iran; Middle Aged; Obesity; Risk Factors

To measure the association between dietary fiber intake and eleven hormones and peptides in postmenopausal breast cancer survivors.. Intake of fiber from food and supplements was measured two to three years after breast cancer diagnosis in 493 postmenopausal women from three western states. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), leptin, C-peptide, insulin-like growth factor-1 (IGF1), and IGF-binding protein-3. Adjusted means of these hormones and peptides were calculated for categories of fiber intake.. High intake of dietary fiber was significantly (P

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; C-Peptide; Cohort Studies; Dietary Fiber; Female; Gonadal Steroid Hormones; Humans; Insulin; Middle Aged; Postmenopause; Prospective Studies; SEER Program; Survivors

Insulin and insulin resistance have been hypothesized to increase the risk of breast cancer as insulin increases breast cell proliferation and inhibits sex hormone binding globulin. Although insulin is directly related to body weight, adiposity is inversely associated with breast cancer risk in premenopausal women but directly related to risk in postmenopausal women. To explore the association between insulin and c-peptide levels and breast cancer risk, we conducted a nested case-control study of predominantly premenopausal women within the Nurses' Health Study II cohort. From 1996 to 1999, blood samples were collected from 29,611 participants. A total of 317 cases were diagnosed after blood collection and before June 2003 and matched to 634 controls; 75% of these women were premenopausal at blood collection. Logistic regression models, controlling for breast cancer risk factors, were used to calculate relative risks (RR) and 95% confidence intervals (95% CI). Among women with fasting blood samples (n = 211 cases), insulin was suggestively inversely associated with breast cancer risk (highest versus lowest quartile: RR, 0.5; 95% CI, 0.3-1.0; P(trend) = 0.06). Among all women, c-peptide was not associated with breast cancer risk (highest versus lowest quartile: RR, 1.1; 95% CI, 0.7-1.7; P(trend) = 0.79); results were similar among fasting samples. These associations did not differ by age, body mass index, or waist-to-hip ratio. Overall, higher levels of insulin and c-peptide were not associated with a higher risk of breast cancer among predominantly premenopausal women.

Topics: Adult; Body Mass Index; Breast Neoplasms; C-Peptide; Canada; Case-Control Studies; Female; Humans; Insulin; Premenopause; Risk; United States

American women are five times more likely to be at risk for breast cancer than women from Asian countries. Epidemiologic studies have linked energy balance to an increased risk of breast cancer, yet few studies have investigated potential mediators of this association with Chinese women. We examined the above association by blood levels of insulin-like growth factors (IGFs), binding proteins, and C-peptide in the Shanghai Breast Cancer Study (SBCS), a case-control study conducted among 1,459 breast cancer cases and 1,556 healthy Chinese women from 1996 and 1998.. In-person surveys were used to collect data on energy intake, anthropometric measures, exercise/sport activity, and occupational activity. The present analyses consisted of 397 cases and 397 controls whose blood samples were measured for levels of IGFs, insulin growth-factor binding protein 3 (IGFBP-3), C-peptide, and the relationship with physical activity status, total energy intake, and body fat distribution.. Body mass index (BMI) and waist-to-hip ratio (WHR) were significantly positively correlated with IGFBP-3 and C-peptide. Adult exercise/sport activity was significantly negatively correlated with insulin-like growth factor 1 (IGF-I). C-peptide levels increased with increasing quartiles of WHR (p for trend<0.01). Additional analyses were performed to evaluate whether the association of energy balance measures with breast cancer risk changed after adjustment for IGFs, IGFBP-3, and C-peptide biomarkers. The associations attenuated, but none of them changed substantially.. Insulin resistance biomarkers may partially explain the association between positive energy balance and breast cancer risk, but future studies are needed to identify the underlying complex biological mechanisms of action for breast cancer prevention.

Topics: Adult; Asian People; Biomarkers; Body Mass Index; Breast Neoplasms; C-Peptide; Case-Control Studies; China; Energy Intake; Energy Metabolism; Exercise; Female; Humans; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Middle Aged; Motor Activity; Risk Assessment; Risk Factors; Waist-Hip Ratio

Epidemiologic evidence suggests obese premenopausal women experience a reduced risk of breast cancer. The mechanism underlying this protection is not fully understood although it is well documented that abdominal obesity may impair ovulatory function and reduce gonadal steroidogenesis. We measured levels of several metabolic markers that are modified by obesity [measured by body mass index (BMI, (weight (kg)/height (m2)))] and play a role in the reproductive axis, including, leptin, insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP3), C-peptide and prolactin in 233 cases and 251 controls participating in a retrospective study of breast cancer in young women conducted in the Seattle/Puget Sound region between 1990 and 1992. Consistent with the finding of a reduced risk with increasing BMI, risks declined with leptin levels, although to a lesser degree with odds ratios (OR) for the highest vs. lowest quartile of BMI=0.34 (95% C.I. 0.3-0.8) and for leptin=0.71 (95% C.I. 0.5-1.3). IGF-I, IGFBP3, C-peptide and prolactin were not related to breast cancer risk in a dose-dependent manner. With the possible exception of leptin, our findings do not suggest that these markers explain the breast cancer protection provided by obesity in premenopausal women.

Topics: Adult; Body Mass Index; Breast Neoplasms; C-Peptide; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Prolactin; Risk Factors

It has been hypothesized that chronic hyperinsulinemia, a major metabolic consequence of physical inactivity and excess weight, might increase breast cancer risk by direct effects on breast tissue or indirectly by increasing bioavailable levels of testosterone and estradiol. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we measured serum levels of C-peptide--a marker for pancreatic insulin secretion--in a total of 1,141 incident cases of breast cancer and 2,204 matched control subjects. Additional measurements were made of serum sex hormone binding globulin (SHBG) and sex steroids. Conditional logistic regression models were used to estimate breast cancer risk for different levels of C-peptide. C-peptide was inversely correlated with SHBG and hence directly correlated with free testosterone among both pre and postmenopausal women. C-peptide and free estradiol also correlated positively, but only among postmenopausal women. Elevated serum C-peptide levels were associated with a nonsignificant reduced risk of breast cancer diagnosed up to the age of 50 years [odds ratio (OR)=0.70, (95% confidence interval (CI), 0.39-1.24); ptrend=0.05]. By contrast, higher levels of C-peptide were associated with an increase of breast cancer risk among women above 60 years of age, however only among those women who had provided a blood sample under nonfasting conditions [OR=2.03, (95% CI, 1.20-3.43); ptrend=0.01]. Our results do not support the hypothesis that chronic hyperinsulinemia generally increases breast cancer risk, independently of age. Nevertheless, among older, postmenopausal women, hyperinsulinemia might contribute to increasing breast cancer risk.

Topics: Adult; Aged; Body Mass Index; Breast Neoplasms; C-Peptide; Case-Control Studies; Europe; Female; Humans; Incidence; Logistic Models; Middle Aged; Multivariate Analysis; Odds Ratio; Postmenopause; Premenopause; Risk Factors

Hormono-metabolic status was assayed before and after month 6, 12, 24, 36, 48, 54 and 60 of therapy in 72 patients with receptor-positive tumors of the breast who completed 5 years of adjuvant tamoxifen (20 mg/24 hrs) or letrozole (2.5 mg/24 hrs). Eleven patients were not followed up, 11 relapsed and had metastases while 50 completed therapy. Significant fall in body mass (Ketle's index), in C-peptide concentration after an insignificant rise and C-peptide/insulin ratio 129 min after glucose loading, low basal blood level of estradiol as well as stable estradiolemia throughout treatment were characteristic of cases of pre-treatment recurrence and metastastic spread. Insulin resistance status, basal serum-estradiol level and fasting its course of development during hormonotherapy should be the subject of further research in criteria for adjuvant hormonotherapy efficacy.

Topics: Aged; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Breast Neoplasms; C-Peptide; Chemotherapy, Adjuvant; Estradiol; Female; Humans; Insulin; Insulin Resistance; Letrozole; Middle Aged; Nitriles; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Time Factors; Triazoles

Members of the insulin-like growth factor family have been associated with breast cancer risk and mammographic breast density, one of the strongest known breast cancer risk indicators. The aim of this cross-sectional study was to examine the association of levels of C-peptide (a marker of insulin secretion) with mammographic breast density among 1,499 healthy women recruited during screening mammography examinations. At time of mammography, blood samples and time since last meal were collected. Plasma C-peptide levels were measured by ELISA method, and mammographic breast density by a computer-assisted method. Spearman's partial correlation coefficients, adjusting for age and time since last meal (when necessary), were used to evaluate the associations. High body mass index and waist-to-hip ratio measurements were independently correlated with high levels of C-peptide (r(s) = 0.173 and r(s) = 0.252, respectively; P < 0.0001) or low breast density (r(s) = -0.389 and r(s) = -0.142, respectively; P < 0.0001). High levels of C-peptide were correlated with low breast density (r(s) = -0.210, P < 0.0001). However, the strength of the negative correlation was substantially reduced and was no longer significant after further adjustment for body mass index and waist-to-hip ratio (r(s) = -0.022, P = 0.41). These results suggest that C-peptide levels are not associated with breast density after complete adjustment for adiposity. Thus, the insulin/C-peptide-breast density relation does not seem to mirror the insulin/C-peptide-breast cancer association.

Topics: Adipose Tissue; Adult; Body Mass Index; Breast; Breast Neoplasms; C-Peptide; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Mammography; Middle Aged; Risk Factors

Obese and physically inactive breast cancer patients may have poorer survival compared with lighter weight and more active women. Several obesity-related and physical activity-related hormones and peptides may explain this association, including insulin, leptin, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3. Few studies have examined the associations between obesity, physical activity, and these hormones/peptides among breast cancer survivors.. To determine whether obesity and physical activity are associated with insulin, IGFs, and leptin levels in a population-based sample of 710 women diagnosed with in situ to stage IIIA breast cancer and enrolled in the Health, Eating, Activity, and Lifestyle Study.. We collected a blood sample and information on physical activity among women diagnosed 2 to 3 years earlier using an interview-administered questionnaire. Trained staff measured weight. C-peptide, leptin, and IGFs were assayed by RIA. Mean hormone levels within body mass index and physical activity categories were adjusted for confounders using analysis of covariance methods.. We observed higher C-peptide (P for trend = 0.0001) and leptin (P for trend = 0.0001) levels and lower IGF-I levels (P for trend = 0.0001) with higher levels of body mass index. We observed lower C-peptide (P for trend = 0.001) and leptin (P for trend = 0.001) levels and higher IGF-I (P for trend = 0.0037) and IGF-binding protein-3 (P for trend = 0.055) levels with higher levels of physical activity.. Increasing physical activity and decreasing body fat may be a reasonable intervention approach toward changing insulin and leptin, thereby potentially influencing breast cancer prognosis.

Topics: Adult; Analysis of Variance; Biomarkers, Tumor; Body Mass Index; Breast Neoplasms; C-Peptide; Chi-Square Distribution; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Leptin; Middle Aged; Motor Activity; Obesity; Prospective Studies; Survivors

Experimental evidence suggests that insulin and insulin-related growth factors may play a role in breast pathology through their mitogenic and anti-apoptotic effects on breast cells. Our objective was to assess the relationship between serum concentrations of insulin-like growth factor-I (IGF-I), its major binding protein (IGFBP-3), the ratio IGF-I:IGFBP-3, c-peptide (a marker of insulin secretion) and the ratio c-peptide:fructosamine (a marker of insulin resistance) and the risk of epithelial hyperplasia (an established breast cancer risk factor) and localized breast cancer among postmenopausal women. Study subjects were patients who provided serum before breast biopsy or mastectomy in 3 hospitals in Grand Rapids, MI between 1977 and 1987. Two case groups, 186 subjects with epithelial hyperplasia of the breast and 185 subjects with localized breast cancer, were compared to 159 subjects with nonproliferative breast changes that have not been associated with increased breast cancer risk. Serum concentrations of IGF-I, IGFBP-3 and the ratio IGF-I:IGFBP-3 were not related to risk of either hyperplasia or breast cancer. For women in the highest quartile of c-peptide or of c-peptide:fructosamine compared to those in the lowest quartile, the odds ratios (ORs) for hyperplasia were 3.0 (95% confidence interval [CI] 1.4-6.5) and 3.3 (95% CI 1.5-7.3), respectively (p trend = 0.02 and 0.02, respectively). The corresponding ORs for breast cancer were 1.5 (95% CI 0.7-3.0) and 1.6 (95% CI 0.8-3.2), respectively (p trend = 0.35 and 0.25, respectively). Our results suggest that insulin and insulin resistance may play a role in breast pathology in postmenopausal women.

Topics: Adult; Aged; Breast; Breast Neoplasms; C-Peptide; Case-Control Studies; Female; Humans; Hyperplasia; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Middle Aged; Odds Ratio; Postmenopause; Risk

Higher levels of circulating Insulin-like Growth Factor (IGF)-I may be associated with higher risks for premenopausal breast cancer. We investigate the associations between circulating levels of IGF-I, its binding proteins (IGFBPs) -1, -2, -3, C-peptide and postmenopausal breast cancer. This is a prospective study nested in 2 Dutch cohorts. The study population included women who were postmenopausal at baseline. Breast cancer cases were identified through linkage with cancer registries. Controls were matched to cases by cohort, age, date of blood donation and place of residence. In total, 149 breast cancer cases and 333 healthy controls were included. Plasma levels of IGF-I, IGFBP-1, -2, -3 and C-peptide were measured by radioimmunoassays. Estimates of the relative risk for breast cancer associated with the quartiles of the peptides' circulating levels were obtained by conditional logistic regression. Models were adjusted for BMI, age at menarche and age at first full-term delivery. For IGF-I, the adjusted OR (95% CI) of the top vs. bottom quartile was 1.1 (0.6; 2.1); for IGFBP-1 it was 0.7 (0.3; 1.3); for IGFBP-2, 1.1 (0.5; 2.4); for IGFBP-3, 1.6 (0.7; 3.5), for C-peptide, 1.3 (0.7; 2.7) and for IGF-I/IGFBP-3 ratio, 1.0 (0.5; 1.8). Our data do not support an association between postmenopausal circulating levels of IGF-I, IGFBP-1, -2, -3, C-peptide and postmenopausal breast cancer.

Topics: Aged; Apoptosis; Breast Neoplasms; C-Peptide; Cohort Studies; Female; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Middle Aged; Odds Ratio; Postmenopause; Prospective Studies; Registries; Risk Factors

Insulin resistance has been suggested to be associated with an increased risk of breast cancer. Insulin sensitivity can be measured using blood C-peptide, a marker of insulin secretion. It is thus conceivable that blood C-peptide levels may be associated with breast cancer risk. To evaluate this hypothesis, we analyzed data from a subset (143 case-control pairs matched by age and status of menopause) of women who participated in the Shanghai Breast Cancer Study, a population-based, case-control study conducted in Shanghai during 1996-1998. Fasting blood samples were collected from study subjects to measure C-peptide levels. For cancer patients, the samples were collected before any cancer therapy. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals related to C-peptide levels. Breast cancer risk was increased with increasing levels of C-peptide (trend test, P = 0.01), with an odds ratio of 2.7 (95% confidence interval = 1.2-5.9) observed for the highest compared with the lowest tertile of C-peptide concentration after adjusting for body mass index and age at the first live birth. The risk was not altered after fully adjusting for other traditional risk factors for breast cancer. This positive association was observed in both pre and postmenopausal women and regardless of the levels of waist-to-hip ratio or body mass index. The results from this study were consistent with the insulin-resistance hypothesis for breast cancer and suggest that increased levels of C-peptide may contribute to the development of breast cancer.

Topics: Adult; Biomarkers; Breast Neoplasms; C-Peptide; Case-Control Studies; Female; Humans; Logistic Models; Middle Aged; Risk Factors

Standard glucose-tolerance test (SGTT) was carried out in 73 patients with endometrial tumors. Elevated concentrations of plasma insulin and C-peptide were established in endometrial carcinoma patients (irrespective of age and reproductive status) after night fast and 120 min after SGTT start, as compared to healthy subjects and breast cancer patients. Obese (BMI index 28 kg/m2) reproductive endometrial carcinoma patients showed pronounced hyperinsulinemia and resistance to insulin. Menopausal patients with endometrial tumors (BMI index < = 28) were characterized by a much faster metabolic clearance of insulin, as compared with all other patients. Therefore, degree of insulin resistance in endometrial carcinoma is determined by both enhanced secretion of insulin and lowered metabolic clearance of this hormone which in turn is associated with obesity.

Topics: Adipose Tissue; Adult; Aged; Blood Glucose; Body Constitution; Body Mass Index; Breast Neoplasms; C-Peptide; Endometrial Neoplasms; Female; Humans; Insulin; Insulin Resistance; Menopause; Middle Aged; Obesity

Insulin-like growth factor I (IGF-I) is a systemic hormone with potent mitogenic and anti-apoptotic properties, which could influence the proliferative behavior of normal breast cells. Limited epidemiological observations suggest that the hormone may play a role in the etiology of breast cancer, especially at pre-menopausal ages. In a prospective case-control study nested within a cohort of New York City women, IGF-I, IGF-binding protein 3 (IGFBP-3) and C peptide were measured in frozen serum samples from 172 pre-menopausal and 115 post-menopausal subjects who were subsequently diagnosed with breast cancer. Subjects were eligible if diagnosed 6 months or more after recruitment into the study (7 to 120 months). Cohort members who matched the cases on age, menopausal status, date of blood sampling and day of menstrual cycle at blood collection served as controls. Post-menopausal breast cancer was not associated with serum IGF-I, IGFBP-3 or C-peptide levels. However, the risk of breast cancer increased with increasing serum concentrations of IGF-I in pre-menopausal women. The odds ratio (OR) for the highest quartile of IGF-I (>256 ng/ml) compared to the lowest (<168 ng/ml) was 1.60 [95% confidence interval (CI) 0.91-2. 81]. The OR decreased to 1.49 (95% CI 0.80-2.79) after adjustment for IGFBP-3. In analyses restricted to subjects who were pre-menopausal at the time of blood sampling and whose cancer was diagnosed before age 50, the top vs. bottom quartile OR increased appreciably to 2.30 (95% CI 1.07-4.94). Adjustment for IGFBP-3 reduced the OR to 1.90 (95% CI 0.82-4.42). There was no association between pre-menopausal breast cancer and IGFBP-3, IGF-I:IGFBP-3 ratio or non-fasting levels of C peptide. Elevated circulating levels of IGF-I may be an indicator of increased risk of breast cancer occurring before age 50.

Topics: Adult; Aged; Breast Neoplasms; C-Peptide; Case-Control Studies; Cohort Studies; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Middle Aged; Postmenopause; Premenopause; Prospective Studies

Postmenopausal overweight women have an increased risk of breast cancer. The link between obesity and breast cancer could be mediated through hyperinsulinemia. Insulin and insulin-like growth factor-1 (IGF-1) stimulate mammary cell proliferation in vitro, and cell proliferation is directly linked to the risk of breast cancer. Our objective was to investigate the relationship between breast cancer and body composition, IGF-1, proinsulin, C-peptide, and fasting insulin. A case-control study was conducted of 438 community-dwelling women aged 53-90 years in 1992-1994 who had no history of cancer at the baseline visit in 1972-1974. Women were excluded who were using estrogen replacement therapy (ERT) or tamoxifen at the 1992-1994 visit, when IGF-1, proinsulin, fasting insulin, and C-peptide levels were measured. Prior ERT, alcohol and tobacco use, exercise, and reproductive history were recorded. Weight, height, and waist/hip ratio were measured. The 45 women with breast cancer had similar baseline body mass indices to the 393 women without breast cancer but had gained significantly more weight between the baseline visit in 1972-1974 and 1992-1994, (age-adjusted relative risk [RR] 1.05/kg, 95% confidence interval [CI] 1.01-1.09, p = 0.016). Proinsulin, fasting insulin, and C-peptide were each significantly positively correlated with both current weight and weight gain. However, levels of these hormones and IGF-1 did not differ significantly between women with and without breast cancer (all 95% CI within 0.996-1.004). Past ERT was significantly more common among women with breast cancer (p = 0.015), and duration of use was significantly longer (age-adjusted RR 1.13 per year of use, 95% CI 1.08-1.18, p = 0.000). The risk of breast cancer was significantly increased in women who had gained weight or used ERT. This increased risk was not associated with circulating levels of IGF-1, fasting insulin, proinsulin, or C-peptide.

Topics: Aged; Aged, 80 and over; Body Weight Changes; Breast Neoplasms; C-Peptide; Case-Control Studies; Estrogen Replacement Therapy; Female; Follow-Up Studies; Humans; Insulin; Insulin-Like Growth Factor I; Life Style; Middle Aged; Obesity; Proinsulin; Risk Factors

Topics: Adult; Aged; Anthropometry; Blood Glucose; Breast Neoplasms; C-Peptide; Case-Control Studies; Female; Humans; Life Style; Middle Aged; Regression Analysis; Risk Factors

Life-style has a major influence on the incidence of breast cancer. To evaluate the effects of life-style related metabolic-endocrine factors on breast cancer risk we conducted a case-control study comparing 223 women aged 38 to 75 years presenting with operable (stage I or II) breast cancer and 441 women of the same age having no breast cancer, who participated in a population-based breast cancer screening program. Women reporting diabetes mellitus were excluded. Sera from 110 women of the same age group presenting with early stage melanoma, lymphoma or cervical cancer were used as a second 'other-cancer control group'. Serum levels of C-peptide were significantly higher in early breast cancer cases compared to controls. The same was found for the ratios C-peptide to glucose or C-peptide to fructosamine, indicating insulin resistance. Sex hormone binding globulin was inversely, triglycerides and available estradiol were positively related to C-peptide. Serum C-peptide levels were related to body mass index (BMI), and to waist/hip ratio (WHR), in particular in controls. However, the relative increase of C-peptide, C-peptide to glucose or C-peptide to fructosamine in cases was independent of BMI or WHR. The log relative risk was linearly related to the log C-peptide levels. Relative risk according to quintiles, and adjusted for age, family history, BMI and WHR, for women at the 80% level was 2.9 as compared with those at the 20% level for C-peptide. Elevated C-peptide or C-peptide to fructosamine values were not observed in the sera from women belonging to the 'other-cancer control group'. This study suggests that hyperinsulinemia with insulin resistance is a significant risk factor for breast cancer independent of general adiposity or body fat distribution.

Topics: Adult; Aged; Blood Glucose; Breast Neoplasms; C-Peptide; Female; Fructosamine; Hexosamines; Humans; Insulin Resistance; Menopause; Middle Aged; Risk

The paper is concerned with the results of investigation of the body composition and albumin circulation using a method of whole-body radiometry, extracellular liquid volume--by a 40K-RP, the level of cortisol, T3, insulin, C-peptide in the blood plasma by a radioimmunoassay in 30 breast cancer patients. A decrease in cellular body mass, an increase in extracellular body mass and total body fat, a decrease in the sizes of all pools and albumin synthesis rate were revealed before the initiation of specific cancer therapy. Ten days after the discontinuation of therapy the above indices returned to normal.

Topics: Adult; Albumins; Body Composition; Breast Neoplasms; C-Peptide; Female; Humans; Hydrocortisone; Insulin; Middle Aged; Postoperative Period; Radioimmunoassay; Radioisotopes; Triiodothyronine