Predicting efficacy of epirubicin by a multigene assay in advanced breast cancer within a Danish Breast Cancer Cooperative Group (DBCG) cohort: a retrospective-prospective blinded study.

PURPOSE: Anthracyclines remain a cornerstone in the treatment of primary and advanced breast cancer (BC). This study has evaluated the predictive value of a multigene mRNA-based drug response predictor (DRP) in the treatment of advanced BC with epirubicin. The DRP is a mathematical method combining in vitro sensitivity and gene expression with clinical genetic information from > 3000 clinical tumor samples. METHODS: From a DBCG cohort, 140 consecutive patients were treated with epirubicin between May 1997 and November 2016. After patient informed consent, mRNA was isolated from archival formalin-fixed paraffin-embedded primary breast tumor tissue and analyzed using Affymetrix arrays. Using time to progression (TTP) as primary endpoint, the efficacy of epirubicin was analyzed according to DRP combined with clinicopathological data collected retrospectively from patients' medical records. Statistical analysis was done using Cox proportional hazards model stratified by treatment line. RESULTS: Median TTP was 9.3 months. The DRP was significantly associated to TTP (P = 0.03). The hazard ratio for DRP scores differing by 50 percentage points was 0.55 (95% CI -0.93, one-sided). A 75% DRP was associated with a median TTP of 13 months compared to 7 months following a 25% DRP. Multivariate analysis showed that DRP was independent of age and number of metastases. CONCLUSION: The current study prospectively validates the predictive capability of DRP regarding epirubicin previously shown retrospectively allowing the patients predicted to be poor responders to choose more effective alternatives. Randomized prospective studies are needed to demonstrate if such an approach will lead to increased overall survival.

Symptoms, symptom distress and health-related quality of life in patients with polycythaemia vera or essential thrombocythaemia during treatment with interferon-alpha.

Sixteen patients with polycythaemia vera or essential thrombocythaemia were treated with interferon-alpha in order to normalize elevated platelets. Patients were followed for 6 months and the frequency and intensity of symptoms and side effects were recorded before and during the study period by the patients and by the doctor. Health-related quality of life was also assessed. The most frequently reported pretreatment symptoms were fatigue, headache and muscle pain. The intensity of fatigue initially increased during treatment and there was no relief of any of the three most frequent symptoms during the treatment period. Common interferon-related symptoms such as fever and chills were most frequently reported after one week. After one month of treatment, symptoms related to the gastrointestinal tract reached a peak. Two patients discontinued treatment during the study period. Another patient suffered severe depression after the study period when still on interferon. There was no difference between the frequency of symptoms recorded by the doctor and that reported by the patients.