Background Adjuvant trastuzumab significantly improves outcomes for patients with HER2-positive early breast cancer. The standard treatment duration is 12 months but shorter treatment could provide similar efficacy while reducing toxicities and cost. We aimed to investigate whether 6-month adjuvant trastuzumab treatment is noninferior to the standard 12-month treatment regarding disease-free survival. Methods This study is an open-label, randomised phase 3 non-inferiority trial. Patients were recruited from 152 centres in the UK. We randomly assigned patients with HER2-positive early breast cancer, aged 18 years or older, and with a clear indication for chemotherapy, by a computerised minimisation process (1:1), to receive either 6-month or 12-month trastuzumab delivered every 3 weeks intravenously (loading dose of 8 mg/kg followed by maintenance doses of 6 mg/kg) or subcutaneously (600 mg), given in combination with chemotherapy (concurrently or sequentially). The primary endpoint was disease-free survival, analysed by intention to treat, with a non-inferiority margin of 3% for 4-year disease-free survival. Safety was analysed in all patients who received trastuzumab. This trial is registered with EudraCT (number 2006-007018-39), ISRCTN (number 52968807), and ClinicalTrials.gov (number NCT00712140).

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Purpose: PSA testing results in unnecessary biopsy and over-diagnosis with consequent overtreatment. Tissue biopsy is an invasive procedure, associated with significant morbidity. More accurate non-or minimum-invasive diagnostic approaches should be developed to avoid unnecessary prostate biopsy and over-diagnosis. We investigated the potential of using circulating tumor cell analysis in cancer diagnosis, particularly in predicting clinically significant prostate cancer in pre-biopsy patients. Material and methods: We enrolled 155 treatment naïve prostate cancer patients and 98 pre-biopsy patients for circulating tumor cell numeration. RNA was extracted from circulating tumor cells from 184 patients for gene expression analysis. Kruskal-Wallis, Spearman's rank, multivariate logistic regression and random forest were applied to assess the association of circulating tumor cells with aggressive prostate cancer. Results: In localized prostate cancer patients, 54% were scored as circulating tumor cell positive, which was associated with higher Gleason score (p=0.0003), risk group (p<0.0001) and clinically significant prostate cancer (p<0.0001). In pre-biopsy group, positive circulating tumor cell score in combination with PSA predicted clinically significant prostate cancer with AUC=0.869. A 12-gene panel prognostic for clinically significant prostate cancer was also identified. Combining PSA level, circulating tumor cell-score and the 12-gene panel, AUC for clinically significant prostate cancer prediction was 0.927 and in cases with multi-parametric MRI data, adding these to multi-parametric MRI significantly increased the prediction accuracy (AUC 0.936 vs 0.629). Conclusions: Circulating tumor cell analysis has the potential to significantly improve patient stratification by PSA and/or multi-parametric MRI for biopsy and treatment.