Survival after breast cancer in women with type 2 diabetes using antidiabetic medication and statins: a retrospective cohort study

Abstract

Background: We assessed survival of breast cancer in women with type 2 diabetes (T2D) treated with metformin, other types of antidiabetic medication (ADM) and statins. Materials and Methods: The study cohort consisted of women with T2D and diagnosed with breast cancer in Finland in 1998─2011. Mortality rates from breast cancer and other causes were analysed by Cox models, and adjusted hazard ratios (HRs) with 95% confidence intervals (Cls) were estimated in relation to the use of different types of medication. Results: The final cohort consisted of 3,533 women. No clear evidence was found for breast cancer mortality being different in metformin users (HR 0.86, 95% Cl 0.63-1.17), but their other-cause mortality appeared to be lower (HR 0.73, 95% Cl 0.55-0.97) in comparison with women using other types of oral ADM. Other-cause mortality was higher among insulin users (HR 1.45, 95% Cl 1.16-1.80) compared with users of other oral ADMs, other than metformin. Prediagnostic statin use was observed to be associated with decreased mortality from both breast cancer (HR 0.76, 95% Cl 0.63-0.92) and other causes (HR 0.75, 95% Cl 0.64-0.87). Conclusions: We did not find any association between ADM use and disease-specific mortality among women with T2D diagnosed with breast cancer. However, interestingly, prediagnostic statin use was observed to predict reduced mortality from breast cancer and other causes. We hypothesise that treating treatment practices of T2D or hypercholesterolaemia of breast cancer patients might affect overall prognosis of women diagnosed with breast cancer and T2D.

Effect of Metformin vs Placebo on Invasive Disease–Free Survival in Patients With Breast Cancer

“…Extrapolation of the findings of this trial to patients with diabetes requires caution because of differing metabolic status (eg, glucose control, insulin resistance, obesity) of patients with vs without diabetes, and reports that breast cancer outcomes are poorer in patients with diabetes for reasons that are not fully understood but may be related to the biological effect of diabetes on breast cancer, delayed breast cancer diagnosis, effects of comorbidity, poor treatment adherence, or other factors. Observational studies involving patients with breast cancer and diabetes have reported inconsistent associations of metformin treatment for diabetes with breast cancer outcomes . A meta-analysis reported better overall and cancer-specific survival in patients with breast cancer and diabetes who received metformin vs other diabetes treatments; however, all of the included observational studies were susceptible to methodological limitations that may have affected results, notably treatment allocation and survival biases .…”

“…A meta-analysis reported better overall and cancer-specific survival in patients with breast cancer and diabetes who received metformin vs other diabetes treatments; however, all of the included observational studies were susceptible to methodological limitations that may have affected results, notably treatment allocation and survival biases . It has been suggested that metformin may act by alleviating the adverse breast cancer prognosis associated with diabetes, possibly through better diabetes control or due to selection of patients with less severe diabetes to receive metformin, rather than through a direct antitumor effect. Because metformin is effective in type 2 diabetes, the results presented herein should not affect the use of metformin to treat diabetes in patients with breast cancer.…”

“…Metformin, a biguanide commonly used to treat type 2 diabetes, has been associated with improved prognosis across breast cancer subtypes in observational studies involving patients with diabetes, although findings have not been consistent . Metformin has also been shown to lower fasting insulin levels and improve obesity associated physiology in patients with breast cancer without diabetes .…”

Survival Risk Analysis of Small Cell Lung Cancer Patients with Pre-Existing Type 2 Diabetes Mellitus: A Single-Center Retrospective Cohort Study

“… 27 A retrospective cohort study also showed that breast cancer patients with preDM given insulin analogs had higher mortality rates than those taking other oral hypoglycemic drugs. 28 Furthermore, it is plausible that synthetic insulin by subcutaneous injection may lead to altered pharmacokinetic profiles and different affinities for receptor-binding, such as insulin receptors, IGFR1 and hybrid receptors, bringing about a stronger cancer-promoting effect than endogenous insulin. 29–31 In addition, in our study, those who had received insulin treatment usually had higher fasting glucose levels, suggesting that they had poor glycemic control.…”

Assessment of Novel Therapeutics for Individualized Breast Cancer Care in the Modern Era: The Role of Metformin in Breast Cancer Therapy

“…8 While this precedence was promising, it is notable that there were some observational studies that did not support metformin's therapeutic potential. 9 Furthermore, in the metastatic breast cancer setting, randomized trials showed no oncologic survival benefit with the addition of metformin to standard regimens. 10,11 The MA.32 randomized clinical trial, an international study of Goodwin et al, recruited non-diabetic patients diagnosed with high-risk breast cancer between 2010 and 2013.…”