Total burden of disease in cancer patients at diagnosis-a Danish nationwide study of multimorbidity and redeemed medication.

BACKGROUND: Multimorbidity is a growing challenge worldwide. In this nationwide study, we investigated the prevalence of multimorbidity and polypharmacy at the time of diagnosis across 20 cancers. METHODS: We conducted a nationwide register-based cohort study of all Danish residents with a first primary cancer diagnosed between 1 January 2005 and 31 December 2015. Multimorbidity was defined as one or more of 20 conditions (131 specific diagnoses) registered in the Danish National Patient Registry < 5 years before the cancer diagnosis. Polypharmacy was defined as five or more medications registered in the Danish National Prescription Registry and redeemed twice 2-12 months before the cancer diagnosis. RESULTS: We included 261,745 patients with a first primary cancer, of whom 55% had at least one comorbid condition at diagnosis and 27% had two or more. The most prevalent conditions at the time of cancer diagnosis were cardiovascular disease, chronic obstructive pulmonary disease, diabetes, stroke and depression/anxiety disorder. Polypharmacy was present in one-third of the cancer patients with antihypertensives, anti-thrombotic agents, anti-hyperlipidaemic agents, analgesics and diuretics as the most prevalent redeemed medications. CONCLUSION: Among patients with a newly established cancer diagnosis, 55% had at least one comorbid condition and 32% were exposed to polypharmacy.

miR-21 Expression in Cancer Cells may Not Predict Resistance to Adjuvant Trastuzumab in Primary Breast Cancer.

Trastuzumab is established as standard care for patients with HER2-positive breast cancer both in the adjuvant and metastatic setting. However, 50% of the patients do not respond to the trastuzumab therapy, and therefore new predictive biomarkers are highly warranted. MicroRNAs (miRs) constitute a new group of biomarkers and their cellular expression can be determined in tumor samples by in situ hybridization (ISH) analysis. miR-21 is highly prevalent and up-regulated in breast cancer and has been linked to drug resistance in clinical and in vitro settings. To determine expression patterns of miR-21 in high-grade breast cancers, we examined miR-21 expression in 22 HER2-positive tumors and 15 HER2-negative high-grade tumors by ISH. The histological examination indicated that patient samples could be divided into three major expression patterns: miR-21 predominantly in tumor stroma, predominantly in cancer cells, or in both stromal and cancer cells. There was no obvious difference between the HER2-positive and HER2-negative tumors in terms of the miR-21 expression patterns and intensities. To explore the possibility that miR-21 expression levels and/or cellular localization could predict resistance to adjuvant trastuzumab in HER2-positive breast cancer patients, we analyzed additional 16 HER2-positive tumors from patients who were treated with trastuzumab in the adjuvant setting. Eight of the 16 patients showed clinical recurrence and were considered resistant. Examination of the miR-21 expression patterns and intensities revealed no association between the miR-21 scores in the cancer cell population (p = 0.69) or the stromal cells population (p = 0.13) and recurrent disease after adjuvant trastuzumab. Thus, our findings show that elevated miR-21 expression does not predict resistance to adjuvant trastuzumab.