Adjuvant Bisphosphonates and Breast Cancer Survival.

Randomized trials have studied bisphosphonates in the adjuvant setting of early breast cancer to investigate their ability to prevent treatment-induced bone loss. Trial results have also suggested their potential to prevent disease recurrence and metastases. These trials are summarized in this review. A recent patient-level meta-analysis by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) finds convincing evidence that adjuvant antiresorptive treatments provide persistent benefits to breast cancer patients in low-estrogen situations and should be considered an important part of the treatment algorithm.

Optimal duration of adjuvant endocrine therapy: how to apply the newest data.

BACKGROUND: The benefit of 5 years of adjuvant endocrine therapy for women with hormone receptor-positive (HR+) breast cancer (BC) is beyond discussion. Nevertheless, the risk of recurrence of luminal BC persists for 15 years or more after diagnosis. Consequently, approaches of extended adjuvant therapy have been investigated in large clinical trials, with the ultimate aim of further reducing the risk of recurrence in patients with HR+ BC. METHODS: A review of recently published trial data is presented to provide a solid basis for discussion. A discussion of the side effects of long-term endocrine treatment, multigenetic tests aiming to identify patients at particular risk, and an outlook for further promising targets are additional aims of this review. CONCLUSION: Extended adjuvant therapy seems beneficial in reducing distant relapse and contralateral BC for a selected group of patients with HR+ BC, particularly if aromatase inhibitors (AIs) are used after initial tamoxifen therapy. However, patients with lower risk of recurrence and initial AI therapy may suffer more from side effects than benefit from extended therapy.

Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study.

BACKGROUND: Patients with refractory or relapsed haematological malignancies have few treatment options and short survival times. Identification of effective therapies with genomic-based precision medicine is hampered by intratumour heterogeneity and incomplete understanding of the contribution of various mutations within specific cancer phenotypes. Ex-vivo drug-response profiling in patient biopsies might aid effective treatment identification; however, proof of its clinical utility is limited. METHODS: We investigated the feasibility and clinical impact of multiparametric, single-cell, drug-response profiling in patient biopsies by immunofluorescence, automated microscopy, and image analysis, an approach we call pharmacoscopy. First, the ability of pharmacoscopy to separate responders from non-responders was evaluated retrospectively for a cohort of 20 newly diagnosed and previously untreated patients with acute myeloid leukaemia. Next, 48 patients with aggressive haematological malignancies were prospectively evaluated for pharmacoscopy-guided treatment, of whom 17 could receive the treatment. The primary endpoint was progression-free survival in pharmacoscopy-treated patients, as compared with their own progression-free survival for the most recent regimen on which they had progressive disease. This trial is ongoing and registered with ClinicalTrials.gov, number NCT03096821. FINDINGS: Pharmacoscopy retrospectively predicted the clinical response of 20 acute myeloid leukaemia patients to initial therapy with 88·1% accuracy. In this interim analysis, 15 (88%) of 17 patients receiving pharmacoscopy-guided treatment had an overall response compared with four (24%) of 17 patients with their most recent regimen (odds ratio 24·38 [95% CI 3·99-125·4], p=0·0013). 12 (71%) of 17 patients had a progression-free survival ratio of 1·3 or higher, and median progression-free survival increased by four times, from 5·7 (95% CI 4·1-12·1) weeks to 22·6 (7·4-34·0) weeks (hazard ratio 3·14 [95% CI 1·37-7·22], p=0·0075). INTERPRETATION: Routine clinical integration of pharmacoscopy for treatment selection is technically feasible, and led to improved treatment of patients with aggressive refractory haematological malignancies in an initial patient cohort, warranting further investigation. FUNDING: Austrian Academy of Sciences; European Research Council; Austrian Science Fund; Austrian Federal Ministry of Science, Research and Economy; National Foundation for Research, Technology and Development; Anniversary Fund of the Austrian National Bank; MPN Research Foundation; European Molecular Biology Organization; and Swiss National Science Foundation.