Hyperthyroidism or hypothyroidism and gastrointestinal cancer risk: a Danish nationwide cohort study

Objective: The association between thyroid dysfunction and gastrointestinal cancer is unclear. Design: We conducted a nationwide population-based cohort study to examine this potential association. Methods: We used Danish medical registries to assemble a nationwide population-based cohort of patients diagnosed with hyperthyroid or hypothyroid disease from 1978 to 2013. We computed standardized incidence ratios (SIRs) with corresponding 95% CIs as measures of the relative risk of each cancer, comparing patients with thyroid dysfunction with that expected in the general population. Results: We included 163,972 patients, of which 92,783 had hyperthyroidism and 71,189 had hypothyroidism. In general, we found an increased risk of all gastrointestinal cancers within the first year after thyroid disease diagnosis. After more than 5 years of follow-up, patients with hyperthyroidism had a slightly increased risk of pancreatic and gallbladder and biliary tract cancer. Patients with hypothyroidism had a slightly increased risk of stomach, anal, liver, gallbladder and biliary tract, and pancreatic cancer after more than 5 years of follow-up, but the observed numbers of cancers were in general similar to the expected. Conclusions: The increased risks of all gastrointestinal cancers in the first year following hyper- or hypothyroidism diagnosis are likely due to detection bias. After more than 5 years of follow-up, there does not seem to be a consistent causal association between thyroid disease and gastrointestinal cancer

Prescriptions for selective cyclooxygenase-2 inhibitors, non-selective non-steroidal anti-inflammatory drugs, and risk of breast cancer in a population-based case-control study

INTRODUCTION. Non-steroidal anti-inflammatory drugs (NSAIDs) prevent the growth of mammary tumours in animal models. Two population-based case-control studies suggest a reduced risk of breast cancer associated with selective cyclooxygenase-2 (sCox-2) inhibitor use, but data regarding the association between breast cancer occurrence and use of non-selective NSAIDs are conflicting. METHODS. We conducted a population-based case-control study using Danish healthcare databases to examine if use of NSAIDs, including sCox-2 inhibitors, was associated with a reduced risk of breast cancer. We included 8,195 incident breast cancer cases diagnosed in 1991 through 2006 and 81,950 population controls. RESULTS. Overall, we found no reduced breast cancer risk in ever users (>2 prescriptions) of sCox-2 inhibitors (odds ratio (OR) = 1.08, 95% confidence interval (95% CI) = 0.99, 1.18), aspirin (OR = 0.98, 95% CI = 0.90-1.07), or non-selective NSAIDs OR = 1.04, (95% CI = 0.98, 1.10)). Recent use (>2 prescriptions within two years of index date) of sCox-2 inhibitors, aspirin, or non-selective NSAIDs was likewise not associated with breast cancer risk (Ors = 1.06 (95% CI = 0.96, 1.18), 0.96 (95% CI = 0.87, 1.06) and 0.99 (95% CI = 0.85, 1.16), respectively). Risk estimates by duration (<10, 10 to 15, 15+ years) or intensity (low/medium/high) of NSAID use were also close to unity. Regardless of intensity, shorter or long-term NSAID use was not significantly associated with breast cancer risk. CONCLUSIONS. Overall, we found no compelling evidence of a reduced risk of breast cancer associated with use of sCox-2 inhibitors, aspirin, or non-selective NSAIDs.Karen Elise Jensen Foundatio

The role of microRNAs as predictors of response to tamoxifen treatment in breast cancer patients

This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. However, resistance to endocrine therapy leads to breast cancer relapse. The recent extension of adjuvant tamoxifen treatment up to 10 years actualizes the need for identifying biological markers that may be used to monitor predictors of treatment response. MicroRNAs are promising biomarkers that may fill the gap between preclinical knowledge and clinical observations regarding endocrine resistance. MicroRNAs regulate gene expression by posttranscriptional repression or degradation of mRNA, most often leading to gene silencing. MicroRNAs have been identified directly in the primary tumor, but also in the circulation of breast cancer patients. The few available studies investigating microRNA in patients suggest that seven microRNAs (miR-10a, miR-26, miR-30c, miR-126a, miR-210, miR-342 and miR-519a) play a role in tamoxifen resistance. Ingenuity Pathway Analysis (IPA) reveals that these seven microRNAs interact more readily with estrogen receptor (ER)-independent pathways than ER-related signaling pathways. Some of these pathways are targetable (e.g., PIK3CA), suggesting that microRNAs as biomarkers of endocrine resistance may have clinical value. Validation of the role of these candidate microRNAs in large prospective studies is warranted

Statin use and breast cancer recurrence in postmenopausal women treated with adjuvant aromatase inhibitors : a Danish population-based cohort study

Purpose: To examine the association between statin use and risk of breast cancer recurrence in a national Danish cohort of postmenopausal breast cancer patients receiving aromatase inhibitors (AI) in the adjuvant setting. Patients and methods: We enrolled all postmenopausal patients diagnosed with stage I–III estrogen receptor positive breast cancer during the years 2007–2017, assigned adjuvant AI treatment, and registered in both the Danish Breast Cancer Group database and the Danish Cancer Registry. We ascertained incident statin exposure (≥ 1 prescription post-diagnosis) from the Danish National Prescription Registry and modeled statins as a time-varying exposure lagged by 6 months. Follow-up began 7 months after diagnosis and continued to the first event of recurrence, death, emigration, 5 years elapsed, or 25th September 2018. We estimated incidence rates of recurrence at 5 years and used Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI), comparing statin exposure with non-exposure. Results: We enrolled 14,773 eligible patients. During the 5 years of follow-up, there were 32 recurrences in 3163 person-years of follow-up among statin-exposed patients, and 612 recurrences in 45,655 person-years among unexposed patients (incidence rate per 1000 person-years: 10.12 [95% CI 6.92–14.28] and 13.40 [95% CI 12.36–14.51], respectively). In multivariable models, any statin exposure was associated with a reduced rate of 5-year breast cancer recurrence (adjusted HR 0.72 [95% CI 0.50–1.04]). Considering only lipophilic statins as exposure the results were similar (adjusted HR 0.70 [95% CI 0.48–1.02]). Conclusions: Statin use was associated with a reduced risk of breast cancer recurrence among postmenopausal patients diagnosed with early stage breast cancer who received adjuvant AI therapy

Circulating lipids and breast cancer prognosis in the Malmö diet and cancer study

Purpose: Examine the association between circulating lipids and breast cancer outcomes in patients enrolled in the Malmö Diet and Cancer Study (MDCS). Patients and methods: Circulating lipid levels were measured in blood sampled upon enrollment in the female MDCS cohort (N = 17,035). We identified all MDCS participants with incident invasive breast cancer diagnosed between 1991 and 2014. Follow-up time began at breast cancer diagnosis and continued until the first event of breast cancer recurrence, death, emigration, or 5 years of follow-up. We estimated the incidence rates of recurrence at 5 years and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI) of breast cancer recurrence as well as all-cause mortality according to cohort-specific tertiles of apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B). Results: We enrolled 850 eligible patients. During the 5 years of follow-up, 90 invasive breast cancer recurrences were diagnosed over 3807 person-years. In multivariable analyses, high baseline levels of Apo B were associated with an increased rate of recurrence (tertile 3 vs. 1, HR = 2.30 [95% CI 1.13–4.68]). However, high baseline levels of Apo B were not associated with all-cause mortality (tertile 3 vs. 1, HR = 1.23 [95% CI 0.68–2.25]). We observed no associations between levels of Apo A-1 and recurrence (tertile 3 vs. 1, HR = 1.34 [95% CI 0.70–2.58]) or all-cause mortality (tertile 3 vs. 1, HR = 1.12 [95% CI 0.61–2.05]). Conclusion: High pre-diagnostic levels of Apo B were associated with an increased risk of recurrence among breast cancer patients. Circulating Apo A-1 was not associated with breast cancer outcomes