THE ROLE OF SOME OBESITY-RELATED BIOCHEMICAL PARAMETERS IN THE INCIDENCE, DIAGNOSIS, AND PROGNOSIS OF POSTMENOPAUSAL BREAST CANCER (original) (raw)
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.
Insulin and related factors in premenopausal breast cancer risk
Breast Cancer Research and Treatment, 1998
Background: Insulin and insulin-like growth factor I (IGF-I) are important mitogens in vitro and in vivo. It has been hypothesized that these factors may play an important role in the development of breast cancer. Methods: A case-control study comparing plasma insulin levels in 99 premenopausal women with newly diagnosed node-negative invasive carcinoma of the breast and 99 age-matched controls with incident biopsied nonproliferative breast disease (NP) was conducted. Women with known diabetes were excluded. Results: For the entire study group, mean age was 42.6 ± 5.1 years and mean weight was 62.9 ± 10.3 kg. After adjustment for age and weight, elevated insulin levels were significantly associated with breast cancer, Odds Ratio (OR) for women in the highest insulin quintile versus the lowest quintile = 2.83 (95% Confidence Interval [CI] 1.22-6.58). There were no statistically significant differences between cases and controls for IGF-I and IGFBP-1 levels. However, after adjustment for age, the association between plasma levels of insulin-like growth factor binding protein 3 (IGFBP-3) and breast cancer approached statistical significance; OR for highest quintile versus lowest quintile of IGFBP-3 being 2.05 (95% CI, 0.93-4.53). All results were independent of diet and other known risk factors for breast cancer. Conclusion: Circulating insulin levels and possibly IGFBP-3 levels are elevated in women with premenopausal breast cancer. This association may reflect an underlying syndrome of insulin resistance that is independent of obesity.
Obesity and prognosis of breast cancer
Obesity Reviews, 2006
Obesity has a complicated relationship to both breast cancer risk and the clinical behaviour of the established disease. It is suggested that obesity is associated with both an increased risk of developing breast cancer risk and worse prognosis after disease onset. In post-menopausal women, various measures of obesity such as body mass index, weight, weight gain and waist : hip ratio have all been positively associated with risk of developing breast cancer. In most but not all case-control and prospective cohort studies, an inverse relationship has been found between weight and breast cancer among pre-menopausal women. Some data suggest that adult weight gain and central obesity increase the risk of pre-menopausal breast cancer. Obesity at the time of diagnosis is thought to be significant as a poor prognostic factor. Obesity is associated with adverse outcomes in both pre-and post-menopausal women with breast cancer. Many cancer survivors seek ways to minimize the risk of recurrence and death because of breast cancer. Despite complex and at times controversial data, enough evidence is available at present to suggest that weight management should be a part of the strategy to prevent the occurrence, recurrence and death because of breast cancer. In this review the effect of obesity on the prognosis of breast cancer is examined in detail.
Insulin, Insulin-Like Growth Factor-I, and Risk of Breast Cancer in Postmenopausal Women
JNCI Journal of the National Cancer Institute, 2009
Breast cancer is the most common malignancy among women in the United States. Approximately 182 000 new cases of breast cancer and more than 40 000 breast cancer -related deaths are expected in 2008 ( 1 ). One of the established risk factors for postmenopausal breast cancer, obesity ( 2 -7 ), has reached epidemic proportions in the United States, and with more than one-third of women older than 40 years currently classifi ed as obese (defi ned as a body mass index [BMI] ≥ 30 kg/m 2 ) ( 8 ), breast cancer incidence rates could soon rise. It is widely hypothesized that the association between obesity and postmenopausal breast cancer partly refl ects the higher than average circulating estrogen levels present in obese women ( 9 ). However, obesity has additional endocrinologic effects that could play a role in breast cancer development.
Relationship Between Obesity, Menopausal Status and Breast Cancer Risks - A Review
Pakistan Journal of Health Sciences
Various research studies have demonstrated that increased concentrations of circulating estrogen levels and higher bioavailability leads to the increased risk of "breast cancer" in "postmenopausal" stages [1, 2]. Additionally, several reports also showed the positive relationship among the menopausal hormones, their changes and the adiposity or "obesity" [3, 4]. Although "obesity" is recognised as the higher risk factor for "breast cancer" especially in "postmenopausal" females, the contrary condition embraces aforementioned to the stage of menopause where the "obesity" is linked with the lower risk in younger women [5]. The consequence of "obesity" on
International Journal of Cancer, 2009
Overweight and obesity is associated with an increased risk of postmenopausal breast cancer. However, less is known about the impact of anthropometric factors on tumor pathology and biology. A Swedish population-based prospective cohort study of 9,685 postmenopausal women not using hormonal replacement therapy (HRT) were followed for an average of 10.3 years during which 305 incident breast cancer cases were diagnosed. Invasive and sufficient tumor material was available in 248 cases. Pathological reevaluation of histological type and grade was conducted. Using a tissue microarray (TMA), the tumor expression of Ki67, HER2, ERa, ERb, PgR, cyclin D1 and p27 was evaluated. Six anthropometric factors: height, weight, body mass index (BMI), waist-and hip circumference and body fat percentage were categorized by quartiles of baseline anthropometric measurements, and relative risks were calculated using multivariate Cox regression models. Invasive breast cancer incidence was increased for women in the higher quartiles of all anthropometric measurements. Height was positively associated with Grade I and ERa-positive tumors. Women in the highest quartiles of weight, BMI, waist-and hip circumference and body fat percentage were all associated with tumors of ductal type, Grade II, low Ki67 index, HER2 negativity and low expression of the oncogene cyclin D1. Obesity was further associated with tumors expressing ERa and PgR but interestingly not ERb. This study confirmed previously described associations between overweight/obesity and increased risk of postmenopausal breast cancer. Furthermore, obesity was associated with tumors expressing several markers corresponding with low malignancy.