Insulin resistance, obesity and breast cancer risk (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...
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, 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.
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.
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...
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
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.
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.