Poor prognosis caused by type 2 diabetes mellitus (T2DM) in women with breast cancer is conferred, while the association between T2DM and breast tumor aggressiveness is still a matter of debate. This study aimed to clarify the differences in breast cancer characteristics, including stage, size, lymph node status, grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (Her2), between patients with and without pre-existing T2DM. PubMed, Embase, and Web of Science were searched for studies from 1 January 2010 to 2 July 2021. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were pooled by using a random effects model. T2DM was significantly associated with tumor stages III/IV versus cancers in situ and stages I/II (pooled ORs (pOR), 95% CI: 1.19; 1.04–1.36, p = 0.012), tumor size >20 versus ≤20 mm (pOR, 95% CI: 1.18; 1.04–1.35, p = 0.013), and lymph node invasion versus no involvement (pOR, 95% CI: 1.26; 1.05–1.51, p = 0.013). These findings suggest that women with T2DM are at a higher risk of late-stage tumors, large tumor sizes, and invasive lymph nodes at breast cancer diagnosis.

Background: The proposed underlying mechanisms of anxiety and depression, and of postoperative neurocognitive disorder (NCD), each include immune system involvement. Therefore, the aims of this study were to investigate the incidence of postoperative NCD 3 months after surgery among oncological patients undergoing surgery and to evaluate the role of preoperative anxiety and depression.Method: A consecutive series of patients (age ≥ 18 years) undergoing surgery for the removal of solid tumors were included (n = 218). Cognitive performance was assessed preoperatively and at 3 months postoperatively. Preoperative anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale.Results: NCD affected 12.3% of elderly patients (age ≥ 70 years, n = 57) at 3 months after surgery, with executive function mostly affected. By contrast, 8.4% of younger patients (age < 70 years, n = 107) were affected, with information processing speed mostly affected. Low educational attainment was a risk factor (OR, 6.0; 95% CI, 1.9–19.0) of overall NCD, whereas preoperative anxiety was associated with decline in the domain of executive function.Conclusion: Postoperative NCD is a complication of oncological surgery for all adults instead of the elderly only. Preoperative anxiety was associated with an increased risk of executive function decline, and low educational attainment was a key factor for overall NCD.

Background: Poor glycemic control prior to cancer diagnosis for patients with preexisting type 2 diabetes (T2DM) may predict a worse cancer diagnosis. We investigated the association between pre-diagnosis glycemic control and all-cause mortality in patients with T2DM who develop cancer. Methods: This prospective cohort study linked data from three sources covering 1989 to 2019: a T2DM benchmarking database, the Netherlands Cancer Registry, and the Personal Records Database. We included patients with T2DM and incident primary breast, colorectal, or prostate cancer (stage 0–III), with target glycemic control defined according to Dutch guidelines. Analysis involved estimating the association between glycemic control and all-cause mortality with Cox proportional hazard models, accounting for individual expected survival relative to the general population and relevant disease (e.g., diabetes duration and medications) and individual (e.g., age and gender) characteristics. Results: Of the 71,648 linked cases, 620 had breast cancer, 774 had colorectal cancer, and 438 had prostate cancer, with follow-up data available for 6.4 (4.2–8.4), 5.6 (2.7–7.6), and 6.3 (4.5–8.2) years, respectively. Compared with patients with pre-diagnosis glycemic control at target, the HRs and 95% confidence intervals for mortality among those with pre-diagnosis glycemic control not at target were 1.40 (1.00–1.96) for breast cancer, 1.45 (1.12–1.88) for colorectal cancer, and 1.39 (0.98–1.98) for prostate cancer. Conclusions: Among patients with T2DM in Dutch primary care, poor glycemic control before diagnosis with breast and colorectal cancer can increase mortality compared with good control. Impact: Glycemic control prior to cancer diagnosis is of prognostic value.

Background: Gliclazide has been suspected to be associated with a lower obesity-related cancer risk; however, current evidence is limited by important methodologic shortcomings. This study aimed to evaluate whether gliclazide is preferred over other sulfonylureas regarding obesity-related cancer risk. Methods: In this prospective cohort study, an annual benchmarking database in Dutch primary care (Zwolle Outpatient Diabetes project Integrating Available CareZODIAC, 1998–2014) was linked to the Netherlands Cancer Registry and the Dutch Personal Record Database. Of the 71,648 patients with type 2 diabetes, we included 26,207 who used sulfonylureas and had no history of cancer or insulin use at baseline. Obesity-related cancer was defined using the latest definition of the World Cancer Research Fund. Cox regression analyses were used to estimate HRs, with both baseline sulfonylurea and cumulative exposure modeled and corrected for baseline covariates. Results: During follow-up for 167,692 person-years, there were 1,111 obesity-related cancer events. For males, the adjusted HRs [95% confidence interval (CI)] for baseline sulfonylurea compared with gliclazide were as follows: glibenclamide, 1.10 (0.92–2.69); glimepiride, 1.13 (0.68–1.84); and tolbutamide, 0.93 (0.59–1.48). For females, these were as follows: glibenclamide, 1.49 (0.72–3.13); glimepiride, 0.96 (0.59–1.54); and tolbutamide, 0.84 (0.54–1.28). The adjusted HRs (95% CI) for one more year of cumulative exposure compared with gliclazide were as follows: glibenclamide, 0.90 (0.71–1.14); glimepiride, 0.96 (0.87–1.06); and tolbutamide, 1.00 (0.92–1.09). For females, these were as follows: glibenclamide, 0.93 (0.77–1.13); glimepiride, 0.99 (0.90–1.10); and tolbutamide, 1.04 (0.96–1.13). Conclusions: Obesity-related cancer risk was comparable between gliclazide and other sulfonylureas. Impact: Gliclazide is not preferred over other sulfonylureas regarding obesity-related cancer risk.

Background: Because of continuous hyperglycemia and hyperinsulinemia and the use of photosensitizing drug, hydrochlorothiazide (HCTZ), the risk of cutaneous squamous cell carcinoma (cSCC) might be increased among patients with diabetes. This study aimed to estimate the risk of cSCC among HCTZ users with type 2 diabetes, and to determine whether thiazide-like diuretics, another drug in the same class with HCTZ, would be safer. Methods: We linked the benchmarking database in Dutch primary care, the Netherlands Cancer Registry, and the Dutch Personal Records Database (1998–2019). All 71,648 patients were included, except for those who had a history of skin cancer prior to cohort entry. We used Cox modeling to estimate the HRs and 95% confidence intervals for cSCC. The model was adjusted by cumulative exposure to each antihypertensive, age, sex, smoking, body mass index, blood pressure, serum creatinine, other confounding drug use at cohort entry, and cohort entry year. Results: There were 1,409 cSCC events (23 among thiazide-like diuretics users), during a follow-up of 679,789 person-years. Compared with no HCTZ use, the adjusted HRs for HCTZ use were 1.18 (1.00–1.40) for ≤2 years, 1.57 (1.32–1.88) for 2 to 4 years, and 2.09 (1.73–2.52) for >4 years. The HR was 0.90 (0.79–1.03) for an additional year of thiazide-like diuretic use. Conclusions: In patients with diabetes, exposure to HCTZ for >2 years is associated with an increased risk of cSCC, whereas no increased risk associated with thiazide-like diuretics was observed. Impact: The potential increased risk of cSCC should be a consideration when prescribing HCTZ, with thiazide-like diuretics offering a safer alternative.