Impact of type 2 diabetes on complications after primary breast cancer surgery: Danish population-based cohort study.

BACKGROUND: Knowledge is sparse on the impact of type 2 diabetes (T2D) on surgical outcomes after breast cancer surgery. This study investigated the association between T2D and risk of complications after primary breast cancer surgery, and evaluated the biological interaction between T2D and co-morbidities. METHODS: Using the Danish Breast Cancer Group clinical database, a cohort of all Danish women diagnosed with early-stage breast cancer during 1996-2022 was created. All patients underwent mastectomy or breast-conserving surgery. Information on prevalent T2D was collected from Danish medical and prescription registries. Surgical complications were defined as hospital diagnoses for medical or surgical complications developing within 30 days after primary breast cancer surgery. The 30-day cumulative incidence proportion of complications was calculated, and Cox regression was used to estimate HRs. Interaction contrasts were computed to determine the additive interaction between T2D and co-morbidities on the incidence rate of complications. RESULTS: Among 98 589 women with breast cancer, 6332 (6.4%) had T2D at breast cancer surgery. Overall, 1038 (16.4%) and 9861 (10.7%) women with and without T2D developed surgical complications, yielding cumulative incidence proportions of 16 (95% c.i. 15 to 17) and 11 (10 to 11)% respectively, and a HR of 1.43 (95% c.i. 1.34 to 1.53). The incidence rate of surgical complications explained by the interaction of T2D with moderate and severe co-morbidity was 21 and 42%, respectively. CONCLUSION: Women with breast cancer and T2D had a higher risk of complications after primary breast cancer surgery than those without T2D. A synergistic effect of T2D and co-morbidity on surgical complications can explain this association.

New Horizons: Epidemiology of Obesity, Diabetes Mellitus, and Cancer Prognosis.

The global prevalence of obesity and diabetes mellitus has increased in parallel with increasing cancer incidence, due to environmental and lifestyle factors and population aging. Metabolic diseases are associated with increased cancer risk, so a growing number of patients with cancer have coexistent obesity and/or diabetes mellitus. In this narrative review, we highlight recent evidence on the clinical impact of obesity and diabetes mellitus on the prognosis of prostate, breast, and colorectal cancer, and provide an overview of the underlying mechanisms. There is evidence that obesity is associated with increased risk of recurrence, and all-cause and cancer-specific mortality among adults with prostate, breast, and colorectal cancer. Diabetes mellitus is associated with increased all-cause and cancer-specific mortality for these 3 cancers, beyond any impact of obesity. Evidence also suggests increased risk of colorectal cancer recurrence in patients with diabetes mellitus. The underlying mechanisms are multifactorial and likely include hormonal imbalances and chronic inflammation that promote cancer cell growth. Obesity and diabetes mellitus are associated with increased risk of complications and side effects of cancer treatment. Associated comorbidities such as impaired kidney function, cardiovascular disease, and neuropathies may preclude the use of guideline cancer treatment and are competing causes of death. Cancer patients with metabolic diseases require a designated clinical program and a multidisciplinary approach involving oncologists, endocrinologists, surgeons, nutritionists, and physiotherapists, to ensure coordinated and optimized patient care.

Breast cancer and incidence of type 2 diabetes mellitus: a systematic review and meta-analysis.

PURPOSE: Breast cancer and its treatments may increase the risk of type 2 diabetes (T2D). We conducted a systematic review and meta-analysis to investigate the association between breast cancer and the incidence of T2D overall, and according to breast cancer treatments. METHODS: We searched PubMed, Embase and references of relevant papers for studies on breast cancer, breast cancer treatment, and subsequent T2D risk. Using random-effects models, we calculated effect estimates and associated 95% confidence intervals of the association between breast cancer, adjuvant breast cancer treatments (i.e., endocrine therapy (tamoxifen, aromatase inhibitors, and combined) and chemotherapy), and subsequent T2D. We used funnel plots to assess publication bias. RESULTS: Among 15 eligible studies, 10 reported on T2D risk after breast cancer, chemotherapy, or endocrine therapy; five studies investigated more than one association. Compared with patients without breast cancer, those with breast cancer and those who received any endocrine therapy had elevated risk of incident T2D (EE = 1.23, 95% CI = 1.13-1.33 and EE = 1.23, 95% CI = 1.16-1.32, respectively). Among breast cancer patients only, the risk of T2D was higher for those who received tamoxifen compared with those who did not receive tamoxifen (EE = 1.28, 95% CI = 1.18-1.38). Due to few studies, analyses investigating T2D risk after treatment with aromatase inhibitors or chemotherapy were inconclusive. CONCLUSION: Our findings suggest an elevated risk of T2D in breast cancer survivors, particularly after tamoxifen therapy. Further research is needed to determine the impact of aromatase inhibitors, and chemotherapy on the incidence of T2D after breast cancer.

Long-term cancer risk in heterozygous familial hypercholesterolemia relatives: a 25-year cohort study.

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) due to low-density lipoprotein receptor (LDLR) mutations predisposes patients to highly elevated levels of cholesterol, and patients are at increased risk of adverse cardiovascular events and other morbidities. Whether the LDLR mutation and high cholesterol levels affect the risk of cancer remains unknown. The purpose of the present study was to assess the long-term cancer risk in HeFH relatives. METHODS: Study participants were identified by cascade screening during 1992-1994. A comparison cohort was matched 10:1 to the relatives from the Danish general population based on birth year, gender and address. All participants were followed until a cancer diagnosis, migration, death, or end of follow-up as of December 31, 2019. The primary endpoint was any incident cancer diagnosis. RESULTS: In total, we included 221 relatives with a median age of 37 years (interquartile range: 27-53 years). A total of 117 (53%) of the relatives carried a LDLR gene mutation. The crude hazard ratio of our primary endpoint did not reveal any differences in cancer incidence in mutation-carrying relatives compared with the general population cohort (1.18; 95% CI, 0.81-1.71). Nonmutation-carrying relatives however had a lower cancer incidence than the general population (0.45: 95% CI, 0.26-0.80). Thus, the risk among mutation-carrying HeFH relatives compared with nonmutation-carrying HeFH relatives was increased (HR: 2.39; 95% CI, 1.24-4.61). CONCLUSION: In Denmark, LDLR mutation-carrying HeFH relatives did not have a different cancer risk than the general population. In contrast, nonmutation-carrying relatives had a lower risk of cancer.

Long-Term Cardiovascular Risk in Heterozygous Familial Hypercholesterolemia Relatives Identified by Cascade Screening.

BACKGROUND: Heterozygous familial hypercholesterolemia increases the risk of adverse cardiovascular events. Whether affected relatives of probands are at increased risk remains unknown. We aimed to evaluate the long-term cardiovascular risk in heterozygous familial hypercholesterolemia relatives with a low-density lipoprotein receptor (LDLR) mutation who were all recommended statin therapy. METHODS AND RESULTS: Participants were identified by cascade screening at Aarhus University Hospital during 1992-1994. A comparison cohort from the Danish general population was matched 10:1 to relatives by birth year and sex. Using medical registries, participants were followed until the event of interest, migration, death, or end of follow-up on December 31, 2014. The primary end point was all-cause mortality and major adverse cardiovascular events comprising myocardial infarction, ischemic stroke, transient ischemic attack, peripheral artery disease, and coronary revascularization. We included 220 relatives. Median age was 37 years (interquartile range: 27-52 years) of which 118 (54%) had an LDLR mutation. By 2004, when prescription data became available, 89% of mutation-carrying participants were taking statins during their follow-up period. Despite frequent use of lipid-lowering medication, the adjusted hazard ratio of the primary end point was 1.65 (95% confidence interval, 1.17-2.33) in mutation-carrying relatives compared with the general population cohort. The risk in non-mutation-carrying relatives was not different from that of the general population cohort (adjusted hazard ratio: 0.85; 95% confidence interval, 0.56-1.29). Comparing mutation-carrying relatives with non-mutation-carrying relatives, the adjusted hazard ratio was 1.94 (95% confidence interval, 1.14-3.31). Results were driven by nonfatal events. CONCLUSION: Heterozygous familial hypercholesterolemia relatives with an LDLR mutation had an increased long-term risk of adverse cardiovascular events.