Repeated measures of serum glucose and insulin in relation to postmenopausal breast cancer

Abstract

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. ' UICCKey words: serum glucose; serum insulin; breast neoplasms; postmenopausal women Risk of postmenopausal breast cancer is increased in association with obesity and diabetes, both of which are characterized by increased insulin resistance, with consequent increases in circulating levels of insulin and glucose.1,2 Insulin promotes cell proliferation 3,4 and enhances breast tumor growth in animal models, 5,6 whereas glucose may exacerbate insulin resistance, 7 favor the selection of malignant clones 8 and provide a growth advantage to cancer cells.9 Therefore, it is plausible that relatively high levels of glucose and/or insulin may play a role in the etiology of breast cancer. The few prospective studies to date that have directly investigated the association between fasting glucose and insulin levels and risk of incident postmenopausal breast cancer have yielded conflicting results.10-18 However, each of these studies was based on a single measurement of glucose and/or insulin at baseline only. Analysis of repeated measurements obtained during follow-up may provide greater insight into the role of these factors in the development of breast cancer and increase the precision of estimates of association. Therefore, we conducted a longitudinal stu...

GPER1 is regulated by insulin in cancer cells and cancer-associated fibroblasts

“…As regards breast cancer, the potential of insulin to contribute to tumor progression has been highlighted in diverse investigations (Rose & Vona-Davis 2012, Sieri et al 2012, Catsburg et al 2014. Nicely supporting these data, in postmenopausal women within the framework of the Women's Health Initiative Observational Study (WHI-OS), the highest tertile of baseline insulin was associated with a twofold risk increase in breast cancer compared with the lowest tertile (Kabat et al 2009). Estrogens perform a fundamental role in hormone-sensitive breast cancer, mainly activating the classical ERs (Hall et al 2001).…”

Does the Mediterranean dietary pattern or the Healthy Diet Index influence the risk of breast cancer in a large British cohort of women?

“…In our study, we were not able to find any statistically significant associations between either the Mediterranean diet score or the WHO HDI and risk of breast cancer. There is some evidence that a Mediterranean diet could impact on diabetes incidence rates (Martinez-Gonzalez et al, 2008), a disease which is likely on the causal pathway for chronic heart disease, but potentially also for breast cancer (Kabat et al, 2009). A recent analysis of the 14 807 women in the Greek EPIC cohort also found no overall association with the Mediterranean diet score and risk of developing breast cancer, however they did find a marginally significant inverse association among postmenopausal women (Trichopoulou et al, 2010).…”

Overweight, Obesity, Diabetes, and Risk of Breast Cancer: Interlocking Pieces of the Puzzle

“…Among five studies providing data, two [26,27] found a direct relationship and three [28 -30] found no consistent association between fasting insulin and breast cancer risk in postmenopausal women. Further, in the WHI 6% random sample of women with a baseline measurement for glucose and insulin, the RR for the highest tertile of insulin was about 2, but this was based on only 190 cases of breast cancer, of which only 75 were invasive [31]. Furthermore, there was no consistent evidence of an association between plasma levels of IGF-1 and breast cancer.…”