[ Diabetes Type 2 ]

Association of diabetes and diabetes treatment with incidence of breast cancer

There is great interest in whether type 2 diabetes and its treatments alter breast cancer risk and prognosis, but previous studies are inconclusive. Overweight is inversely related to premenopausal breast cancer, but there is definite evidence that, as compared with normal weight women, the relative risk (RR) for postmenopausal breast cancer is around 1.5 for overweight women and >2 for obese women, and that the association is stronger in elderly women. In this cross-sectional study, women aged 55-79 years living in Ontario, Canada, with newly diagnosed diabetes from 1994 to 2002 were identified from a validated, population-based database (N = 82,390). MDA-MB-231, MCF 7, and human umbilical vein endothelial cells (HUVECs) were treated with normal HDL from healthy controls (N-HDL), HDL from breast cancer patients (B-HDL), or HDL from breast cancer patients complicated with type 2 diabetes mellitus (BD-HDL), and the cell adhesion abilities were determined. This marine treasure is a nutrient powerhouse in any form. “Increasing the duration of overnight fasting could be a novel strategy to reduce the risk of developing breast cancer,” said lead author Catherine Marinac, a doctoral student at University of California, San Diego School of Medicine. Breast cancer patients with diabetes were significantly more likely to present with advanced-stage breast cancer than those without diabetes.

The odds ratio for the association between diabetes and risk of developing breast cancer was elevated with statistical significance (OR = 2.96; 95 % CI =1.36.3; pvalue=0.004). Xu H, Chen K, Jia X, et al. Moreover, patients with diabetes without other comorbidity had a similar overall survival as patients without any comorbidity. In Europe alone, by 2011 there were around 52.6 million people with diabetes, and 10 % of deaths in adults were attributed to this disease [1]. In fact, about 80 percent of people who have pancreatic cancer also have glucose intolerance (blood sugar levels that are high, but not yet at diabetic levels) or diabetes, researchers have found, researchers say. It is well-known that hyperglycemia in surgical patients delays wound healing [6],[7] and increases the likelihood of postsurgical infection [8],[9] and cardiovascular events.[10],[11] Some recent studies have reported that pharmacotherapy, including hormonal and chemotherapeutic agents for breast cancer, may influence poor glycemic control;[12],[13] thus, pharmacotherapy for breast cancer with diabetes could be a further burden for the Japanese health care system. Substantial evidence supports that type 2 diabetes is a risk factor for the development of numerous types of cancer, including those of the pancreas, liver, stomach, colorectum, kidney, bladder, postmenopausal breast and endometrium [3].

Still, a number of important questions remain unanswered. But this small risk is balanced by the need to treat the original breast cancer. Second, the latency period from diabetes exposure to cancer risk is unknown. C. Finally, anti-diabetes medication may also modulate the risk of cancer, and further research is needed to disentangle the effects of diabetes from those derived from its treatment. Take heart, though, there are  many things we can do about this. There is epidemiological evidence showing that the association between breast cancer and its risk factors vary according to the expression of tumor receptors.

However, few previous reports have explored the possible role of diabetes on specific breast cancer subtypes [7]. The objective of this report is to evaluate the association between diabetes and diabetes treatment with incidence of postmenopausal breast cancers, overall and by specific subtypes. Studies also indicate that fasting glucose levels ≥ 126 mg/dl, which is cutoff for defining the T2DM were related to an increased risk for the carcinogenesis of the breast [34, 35]. Incidence cases of histologically confirmed breast tumors were recruited from 23 Spanish public hospitals from 2008 to 2013. The overall survival (OS) rate was calculated from the date of surgery to the date of mortality or last follow-up visit. Age- and region-matched population controls were randomly selected from primary care center lists. ER-positive and HER2-positive tumors are considered to be an endocrine-resistant subtype of breast cancer.

All participants who agreed to participate signed an informed consent, and the study was formally approved by the corresponding ethics committee of each area. The MCC-Spain study also followed the Declaration of Helsinki and the Spanish Personal Data Protection Act of 1999. Both cases and controls were interviewed by trained personnel, collecting data on socio-demographic factors, health behaviors, gynecologic/obstetric history, preexisting medical conditions, treatments received and family history of cancer. Waist and hip circumferences were measured at the time of the interview. In the present study, we initially included all cases of postmenopausal breast cancer (N = 1018) and their matched controls (N = 1243). We then excluded women with lack of information on diabetes status (N = 43 women) and, in order to reduce the probability of including type 1 diabetic individuals as exposed, women who had been diagnosed of diabetes before the age of 45 (N = 19 women). To allow for a minimum latency period and to avoid that the clinical conditions that lead to diabetes and cancer diagnosis could overlap, we also excluded women who had been diagnosed of diabetes ≤1 year before the diagnosis of cancer (N = 12 women;).

Finally, to obtain effect estimators adjusted by BMI, we excluded 177 women with missing values, leading to a final sample of 916 cases/1094 controls. In a sensitivity analysis, we included these participants and imputed their BMI to check the consistency of our results (data not shown). Time since diagnosis was computed as the age at interview minus the age at fist diagnosis of diabetes. To allow for a minimum latency period, all potential confounders that could be modified by the disease (tobacco and alcohol consumption, energy intake, physical exercise) were censored to 1 year prior to the interview. Self-reported diabetic drugs were classified according to the Anatomical Therapeutic Chemical Classification System of the World Health Organization. Because the number of participants per subgroup was small, only two main categories are considered for this report: A10A (insulin and analogs) and A10B (blood glucose-lowering drugs, excluding insulin). In accordance with this, diabetic participants were classified into three groups if they had ever received this treatment for at least 1 year: (1) conservative therapy, (2) treatment with blood glucose-lowering drugs and (3) treatment with insulin (±anti-diabetic agents).

Trained personnel reviewed all pathologic records and registered information regarding histological type and receptor status in breast cancer cases. Breast tumors were divided into groups according to the presence/absence of the estrogen receptor (ER), progesterone receptor (PR) or the human epidermal growth factor receptor (HER2) as follows: (1) hormone receptor-positive tumors (ER+ or PR+ with HER2−); (2) HER2+ tumors (independent of ER or PR) and (3) triple-negative (TN) tumors (ER−, PR− and HER2−). Descriptive statistics of participant characteristics were calculated for both cases and controls by diabetes status (Table ). To evaluate the association between diabetic status and cancer risk, we fitted multivariate logistic mixed models, including the study region as a random effect term, and adjusted for age, educational level, BMI, age of menarche, age at first birth, existence of previous biopsies and family history of the studied cancer. To study whether diabetes treatment could be associated with cancer incidence, we followed two strategies. First, we evaluated the risk of cancer associated with different treatment regimens (conservative, oral medication, insulin ± oral medication) using the non-diabetic population as the reference category. Then, we quantified the association between duration of use of specific anti-diabetic drugs and cancer risk in the diabetic subgroup.

To explore whether the effects of diabetes, diabetes treatment or diabetes duration could differ by cancer subtype, multinomial logistic models were fitted, considering in each case the aforementioned subtypes of breast cancer. Heterogeneity of effects was tested using a Wald test comparing the coefficients obtained for the different subtypes. As sensitivity analyses, we first adjusted all models for waist-to-hip circumference instead of BMI. Second, we further adjusted the models for tobacco and alcohol consumption, energy intake and physical exercise when this information was available (N = 1732). Third, we explored the results of including participants with missing values in BMI (N = 177) after performing multiple imputation on this variable. Fourth, we further adjusted models on diabetes treatment by diabetes duration. Finally, we evaluated whether the effect of diabetes varied across categories of BMI by introducing an interaction term between the independent variable and BMI (non-obese vs.

obese). All sensitivity analyses gave similar results (data not shown in tables). Table  shows the main characteristics of the study participants. Compared to their controls, cases were slightly younger and had greater BMI values. Diabetic women were older, had lower education levels, higher prevalence of obesity and were more likely to be diagnosed with TN tumors than those without diabetes.

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