THE ROLE OF SOME OBESITY-RELATED BIOCHEMICAL PARAMETERS IN THE INCIDENCE, DIAGNOSIS, AND PROGNOSIS OF POSTMENOPAUSAL BREAST CANCER (original) (raw)
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International journal of oncology, 2012
The past two decades have seen a drastic increase in obesity rates in Western societies and emerging countries. As such, it has become increasingly important to understand the molecular mechanisms by which obesity affects the risk of developing associated co-morbidities. The present study aimed at identifying the effect of insulin on breast cancer and breast epithelial cells, reflective of obesity-associated hyperinsulinaemia, as a molecular explanation for the increased risk of oestrogen receptor-negative postmenopausal breast cancer in obese women. Both of the examined breast cancer cell lines (MDA‑MB-231 and SK-BR-3) showed intact insulin signalling (insulin receptor phosphorylation and activation of phosphoinositol-3 kinase and mitogen-activated protein kinase cell signalling pathways), with MDA-MB-231 cells showing aberrantly amplified insulin signalling. Insulin did not induce a physiologically significant change in proliferation or apoptosis in either cell line. MDA-MB-231 ce...
Insulin resistance, obesity and breast cancer risk
Maturitas, 2008
Breast cancer (BC) is one of the most important problems of public health. Among the avoidable risk factors during a woman's life, overweight and obesity are very important ones. Furthermore they are increasing worldwide. The risk of breast cancer is traditionally linked to obesity in postmenopausal women; conversely, it is neutral or even protective in premenopausal women. Since the initiator and promoter factors for BC act over a long time, it seems unlikely that the menopausal transition may have too big an impact on the role of obesity in the magnitude of the risk. We reviewed the literature in an attempt to understand this paradox, with particular attention to the body fat distribution and its impact on insulin resistance. The association of insulin resistance and obesity with BC risk are biologically plausible and consistent. Estradiol (E2) and IGFs act as mitogens in breast cancer cells. They act together and reciprocally. However the clinical and biological methods to assess the impact of insulin resistance are not always accurate. Furthermore insulin resistance is far from being a constant feature in obesity, particularly in premenopausal women; this complicates the analysis and explains the discrepancies in large prospective trials. The most consistent clinical feature to assess risk across epidemiological studies seems to be weight gain during lifetime. Loss of weight is associated with a lower risk for postmenopausal BC compared with weight maintenance. This observation should be an encouragement for women since loss of weight may be an effective strategy for breast cancer risk reduction.
Insulin, estradiol levels and body mass index in pre- and post-menopausal women with breast cancer
Journal of Radiation Research and Applied Sciences, 2015
Breast cancer is the most common cancer among women where it is associated with considerable morbidity and mortality. The aim of this study was to investigate the association between insulin, estradiol levels and body mass index (BMI) as risk factors for breast cancer. Methods: 80 women newly diagnosed with breast cancer stage IeIII invasive breast cancer, were selected randomly and divided in two groups: 40 pre-menopausal aged 26e46 years and 40 post-menopausal aged 52e90 years. Radioimmunoassay used for serum insulin levels measurement, ELISA was used for estradiol levels and BMI calculated by weight (kg)/height (m 2). Results: Insulin levels in premenopausal (16.6 ± 10.5) and postmenopausal (17.9 ± 8.8); breast cancer patients showed increasing pattern from the normal levels (4.0e16.0 mIU/ml). While, the levels of estradiol in premenopausal (233 ± 173) and postmenopausal, (549 ± 468); estradiol level in postmenopausal was higher than normal level (50e300 ng/ml), its level showed significantly increase in postmenopausal breast cancer (P.Value ¼ 0.001). Conclusion: Insulin levels increased in pre-and postmenopausal breast cancer patients while estradiol levels do not showed association with premenopausal breast cancer. High BMI, high insulin and estradiol levels in postmenopausal women may be considered as risk factors for breast cancer.
Breast Cancer Risk in Metabolically Healthy but Overweight Postmenopausal Women
Adiposity is an established risk factor for postmenopausal breast cancer. Recent data suggest that high insulin levels in overweight women may play a major role in this relationship, due to insulin's mitogenic/antiapoptotic activity. However, whether overweight women who are metabolically healthy (i.e., normal insulin sensitivity) have elevated risk of breast cancer is unknown. We investigated whether overweight women with normal insulin sensitivity [i.e., homeostasis model assessment of insulin resistance (HOMA-IR) index, or fasting insulin level, within the lowest quartile (q1)] have increased breast cancer risk. Subjects were incident breast cancer cases (N ¼ 497) and a subcohort (N ¼ 2,830) of Women's Health Initiative (WHI) participants with available fasting insulin and glucose levels. In multivariate Cox models, metabolically healthy overweight women, defined using HOMA-IR, were not at elevated risk of breast cancer compared with metabolically healthy normal weight women [HR HOMA-IR , 0.96; 95% confidence interval (CI), 0.64-1.42]. In contrast, the risk among women with high (q3-4) HOMA-IRs was elevated whether they were overweight (HR HOMA-IR , 1.76; 95% CI, 1.19-2.60) or normal weight (HR HOMA-IR , 1.80; 95% CI, 0.88-3.70). Similarly, using fasting insulin to define metabolic health, metabolically unhealthy women (insulin q3-4) were at higher risk of breast cancer regardless of whether they were normal weight (HR insulin , 2.06; 95% CI, 1.01-4.22) or overweight (HR insulin , 2.01; 95% CI, 1.35-2.99), whereas metabolically healthy overweight women did not have significantly increased risk of breast cancer (HR insulin , 0.96; 95% CI, 0.64-1.42) relative to metabolically healthy normal weight women. Metabolic health (e.g., HOMA-IR or fasting insulin) may be more biologically relevant and more useful for breast cancer risk stratification than adiposity per se. Cancer Res; 75(2); 270-4. Ó2014 AACR.
Insulin, Estrogen, Inflammatory Markers and Risk of Benign Proliferative Breast Disease
Cancer Research, 2014
Women with benign proliferative breast disease (BPBD) are at increased risk for developing breast cancer. Evidence suggests that accumulation of adipose tissue can influence breast cancer development via hyperinsulinemia, increased estrogen, and/or inflammation. However, there are limited data investigating these pathways with respect to risk of BPBD. We evaluated serologic markers from these pathways in a case-control study of postmenopausal women nested within the Women's Health Initiative Clinical Trial. Cases were the 667 women who developed BPBD during follow-up, and they were matched to 1,321 controls. Levels of insulin, estradiol, C-reactive protein (CRP), and adiponectin were measured in fasting serum collected at baseline. Conditional logistic regression models were used to estimate ORs for the association of each factor with BPBD risk. Among nonusers of hormone therapy, fasting serum insulin was associated with a statistically significant increase in risk of BPBD (OR for highest vs. lowest quartile ¼ 1.80; 95% confidence interval, CI, 1.16-2.79; P trend ¼ 0.003) as were levels of estradiol (OR for highest vs. lowest tertile ¼ 1.89; 95% CI, 1.26-2.83; P trend ¼ 0.02) and CRP (OR for highest vs. lowest quartile ¼ 2.46; 95% CI, 1.59-3.80; P trend < 0.001). Baseline adiponectin level was inversely associated with BPBD risk (OR for highest vs. lowest quartile ¼ 0.47; 95% CI, 0.31-0.71; P trend < 0.001). These associations persisted after mutual adjustment, but were not observed among users of either estrogen alone or of estrogen plus progestin hormone therapy. Our results indicate that serum levels of estrogen, insulin, CRP, and adiponectin are independent risk factors for BPBD and suggest that the estrogen, insulin, and inflammation pathways are associated with the early stages of breast cancer development. Cancer Res; 74(12); 3248-58. Ó2014 AACR.
The Obesity and the Risk of Breast Cancer among Pre and Postmenopausal Women
Asian Pacific journal of cancer prevention : APJCP, 2018
Background: Breast cancer is the most common cancer among women worldwide and the obesity is one of the factors related to the risk of breast cancer mainly in postmenopausal women. This study investigated the association between obesity in pre- and postmenopausal women with the development of breast cancer and the expression of estrogen, progesterone, HeR-2 and triple-negative (TN) receptors. Methods: A case-control study was conducted on 100 patients with recently diagnosed breast cancer and 400 age-matched controls. The women were divided into pre- and post-menopausal groups. Results: The multivariate analysis showed that postmenopausal women with a BMI ≥ 30 kg/m2 at pre-diagnosis and at the most recent measurement were 1.50 (95% CI 1.06-2.13) and 1.56 (95% CI 1.11-2.21) times more likely to develop breast cancer, respectively. These women had a prevalence of obesity of 27.7% when considering pre-diagnosis BMI and 29.4% when analyzing the indicator of recent BMI. When only the cas...
2000
Objective: Insulin resistance and increased levels of serum steroids have been hypothesized to be relevant etiological factors for breast cancer. Measurements of markers of insulin resistance and elevated serum steroids may identify women at high risk for breast cancer. The present study analyzed the association of breast cancer with markers of insulin resistance and elevated serum sex steroids, abdominal adiposity, increase in sebum production and hirsutism in a case±control study nested in a prospective cohort study. Methods: Between 1987 and 1992, 10,786 women (aged 35±69) were recruited in a prospective study on breast cancer in Italy, the ORDET study. Women with a history of cancer and on hormone therapy were excluded at baseline. At recruitment, abdominal adiposity was calculated from the ratio of waist-to-hip circumferences. Sebum production was measured on the forehead under standardized conditions using a sebumeter. Nine androgensensitive body areas were evaluated for hirsutism and a total hirsutism score was computed. After an average of 5.5 years of follow-up, 144 breast cancer cases were identi®ed among the participants of the cohort. For each breast cancer case, four matched controls were randomly chosen from members of the cohort who did not develop breast cancer during the follow-up period. Results: Waist-to-hip ratio was associated with breast cancer in premenopausal women: age and body mass index (BMI) adjusted relative risk (RR) for the highest tertile of waist-to-hip ratio was 2.2 [95% con®dence interval (CI) 1.04±4.75], p for trend 0.03. In the analysis conducted within strata of BMI, the eect of waist-to-hip ratio was con®ned to the group of thinner women: RR for the highest tertile of waist-to-hip ratio was 3.4 (95% CI 1.2±9.5). Sebum production and hirsutism were associated with breast cancer among postmenopausal women. Age and BMI adjusted RRs for the upper tertiles were 2.2 (95% CI 1.1±4.6), p for trend 0.01, and 2.3 (95% CI 1.1±4.9), p for trend 0.03, for sebum and hirsutism, respectively. Conclusion: These results add evidence for a role of hormones and metabolic alterations in breast cancer etiology and for dierent relations of these risk factors with breast cancer in premenopausal and postmenopausal women.
Journal of Experimental & Clinical Cancer Research, 2013
Background: Metabolic Syndrome (MS) has been correlated to breast carcinogenesis. MS is common in the general population (34%) and increases with age and body mass index. Although the link between obesity, MS and hormone related cancer incidence is now widely recognized, the molecular mechanisms at the basis of such increase are still poorly characterized. A crucial role is supposed to be played by the altered insulin signalling, occurring in obese patients, which fuels cancer cell growth, proliferation and survival. Therefore we focused specifically on insulin resistance to investigate clinically the potential role of insulin in breast carcinogenesis. Methods: 975 patients were enrolled and the association between MS, insulin resistance, and breast cancer was evaluated. Women were stratified by age and menopausal status. Insulin resistance was measured through the Homeostasis Model Assessment score (HOMA-IR). The cut off value to define insulin resistance was HOMA-IR ≥ 2.50. Results: Higher prevalence of MS (35%) was found among postmenopausal women with breast cancer compared to postmenopausal healthy women (19%) [OR 2.16]. A broad range of BMI spanning 19-48 Kg/m 2 was calculated. Both cases and controls were characterized by BMI ≥ 25 Kg/m 2 (58% of cases compared to 61% of controls). Waist circumference >88 cm was measured in 53% of cases-OR 1.58-(95% CI 0.8-2.8) and in 46% of controls. Hyperinsulinemia was detected in 7% of cases-OR 2.14 (95% CI 1.78-2.99) and only in 3% of controls. HOMA-IR score was elevated in 49% of cases compared to 34% of controls [OR 1.86], suggesting that insulin resistance can nearly double the risk of breast cancer development. Interestingly 61% of women operated for breast cancer (cases) with HOMA-IR ≥ 2.5 presented subclinical insulin resistance with fasting plasma glucose levels and fasting plasma insulin levels in the normal range. Both android fat distribution and insulin resistance correlated to MS in the subgroup of postmenopausal women affected by breast cancer.
Repeated measures of serum glucose and insulin in relation to postmenopausal breast cancer
2009
Experimental and epidemiological evidence suggests that circulating glucose and insulin may play a role in breast carcinogenesis. However, few cohort studies have examined breast cancer risk in association with glucose and insulin levels, and studies to date have had only baseline measurements of exposure. We conducted a longitudinal study of postmenopausal breast cancer risk using the 6% random sample of women in the Women's Health Initiative clinical trials whose fasting blood samples, provided at baseline and at years 1, 3 and 6, were analyzed for glucose and insulin. In addition, a 1% sample of women in the observational study, who had glucose and insulin measured in fasting blood samples drawn at baseline and in year 3, were included in the analysis. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for the association of baseline and follow-up measurements of serum glucose and insulin with breast cancer risk. All statistical tests were 2-sided. Among 5,450 women with baseline serum glucose and insulin values, 190 incident cases of breast cancer were ascertained over a median of 8.0 years of follow-up. The highest tertile of baseline insulin, relative to the lowest, was associated with a 2-fold increase in risk in the total population (multivariable hazard ratio 2.22, 95% confidence interval 1.39-3.53) and with a 3-fold increase in risk in women who were not enrolled in the intervention arm of any clinical trial (multivariable hazard ratio 3.15, 95% confidence interval 1.61-6.17). Glucose levels showed no association with risk. Analysis of the repeated measurements supported the results of the baseline analysis. These data suggest that elevated serum insulin levels may be a risk factor for postmenopausal breast cancer. ' 2009 UICC
Metabolic Syndrome and Related Disorders, 2010
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 ¼ 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) ¼ 10, P < 0.001, partial eta squared ¼ 0.03]. The interaction of central obesity on this association was also significant [F(54) ¼ 37, P < 0.001, partial eta squared ¼ 0.11]. We conclude that the noted linkage between insulin resistance and breast cancer may indicate an underlying pathology of mammary carcinogenesis.