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

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.

Association of antidiabetic medication and statins with breast cancer incidence in women with type 2 diabetes.

PURPOSE: To address the possible association between the use of metformin, other forms of antidiabetic medication (ADM) and statins with the incidence of breast cancer in women with type 2 diabetes (T2D). METHODS: Data were collected from a Finnish nationwide diabetes database (FinDM). The study cohort consisted of women diagnosed with T2D in 1996-2011 in Finland. In full-cohort analysis, Poisson regression was used to estimate hazard ratios (HRs) in relation to use of metformin, insulin, other forms of oral ADM and statins. In nested case-control analysis, up to 20 controls were matched for age and duration of diabetes to each case of breast cancer. Conditional logistic regression was used to estimate HRs in relation to medication use and cumulative use of different forms of ADM, and statins. RESULTS: 2300 women were diagnosed with breast cancer during follow-up. No difference in breast cancer incidence was observed between metformin users [HR 1.02, 95% confidence interval (CI) 0.93-1.11] or statin users (HR 0.97, 95% CI 0.89-1.05) compared with non-users. In nested case-control analysis the results were similar. Use of insulin (HR 1.18, 95% CI 1.03-1.36) was associated with a slightly increased incidence of breast cancer. CONCLUSIONS: No evidence of an association between the use of metformin or statins and the incidence of breast cancer in women with T2D was found. Among insulin users, a slightly higher incidence of breast cancer was observed.

Association of antidiabetic medication and statins with survival from ductal and lobular breast carcinoma in women with type 2 diabetes.

We investigated the survival of female patients with pre-existing type 2 diabetes (T2D) diagnosed with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of breast, in relation to the use of metformin, other antidiabetic medication (ADM) and statins. The study cohort consisted of 3,165 women (2,604 with IDC and 561 with ILC). The cumulative mortality from breast cancer (BC) and from other causes was calculated using the Aalen-Johansen estimator. The cause-specific mortality rates were analysed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of different medications. No evidence of an association of metformin use with BC mortality was observed in either IDC (HR 0.92, 95% confidence interval [CI] 0.64-1.31) or ILC (HR 0.68, 95% CI 0.32-1.46) patients, when compared to other oral ADMs. The mortality from other causes was found to be lower amongst the IDC patients using metformin (HR 0.64, 95% CI 0.45-0.89), but amongst ILC patients the evidence was inconclusive (HR 1.22, 95% CI 0.64-2.32). Statin use was consistently associated with reduced mortality from BC in IDC patients (HR 0.77, 95% CI 0.62-0.96) and ILC patients (HR 0.59, 95% CI 0.37-0.96), and also mortality from other causes in IDC patients (HR 0.81, 95% CI 0.67-0.96) and in ILC patients (HR 0.66, 95% CI 0.43-1.01). We found no sufficient evidence for the possible effects of metformin and statins on the prognosis of BC being different in the two histological subtypes.

Primary Ciliary Signaling in the Skin-Contribution to Wound Healing and Scarring.

Primary cilia (PC) are solitary, post-mitotic, microtubule-based, and membrane-covered protrusions that are found on almost every mammalian cell. PC are specialized cellular sensory organelles that transmit environmental information to the cell. Signaling through PC is involved in the regulation of a variety of cellular processes, including proliferation, differentiation, and migration. Conversely, defective, or abnormal PC signaling can contribute to the development of various pathological conditions. Our knowledge of the role of PC in organ development and function is largely based on ciliopathies, a family of genetic disorders with mutations affecting the structure and function of PC. In this review, we focus on the role of PC in their major signaling pathways active in skin cells, and their contribution to wound healing and scarring. To provide comprehensive insights into the current understanding of PC functions, we have collected data available in the literature, including evidence across cell types, tissues, and animal species. We conclude that PC are underappreciated subcellular organelles that significantly contribute to both physiological and pathological processes of the skin development and wound healing. Thus, PC assembly and disassembly and PC signaling may serve as attractive targets for antifibrotic and antiscarring therapies.