Off-trial evaluation of bisphosphonates in patients with metastatic breast cancer

BACKGROUND: Bisphosphonate therapy has been readily accepted as standard of care for individuals with bone metastases from breast cancer. In this study we determined whether the proportion of patients experiencing a skeletal related event (SRE) in a clinical practice population was similar to that observed in phase III randomized controlled studies. METHODS: A retrospective chart review was conducted of 110 patients receiving intravenous bisphosphonates for advanced breast cancer. The proportion of patients experiencing at least one SRE after 12 months of therapy was determined. SRE included vertebral or non-vertebral fracture, cord compression, surgery and/or radiotherapy to bone. RESULTS: The proportion of patients who had an SRE was 30% (28 individuals) and the median time to first event was greater than 350 days. Non-vertebral events and radiotherapy were the most frequent type of SRE, while cord compression and hypercalcaemia were rare (1%). Most patients in the study had bone-only disease (58.2%) and most had multiple bone lesions. In the first 12 months the mean duration of exposure to intravenous bisphosphonates was 261 days and most patients remained on treatment until just before death (median 27 days). CONCLUSION: This study suggests that the rate of clinically relevant SREs is substantially lower than the event rate observed in phase III clinical trials. We attribute this lower rate to observational bias. In the clinical trial setting it is possible that over-detection of skeletal events occurs due to the utilisation of regular skeletal survey or radionucleotide bone scan, whereas these procedures are not routine in clinical practice. Phase IV observational studies need to be conducted to determine the true benefits of bisphosphonate therapy in order to implement rationale use of bisphosphonates

Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomised, placebo-controlled phase III studies

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Molecular characterization of a recombinant HIV type 1 isolate (A/G/E/?): Unidentified regions may be derived from parental subtype E sequences

Recombination is one of several factors contributing to the genetic diversity of HIV-1, which is divided into group M (itself comprising 11 subtypes, A-K) and two other groups named O and N, In the present study, the full-length genome of an HIV-1 isolate obtained from a Greek subject (GR17) infected in the Democratic Republic of the Congo (formerly Zaire) was analyzed to reveal a novel mosaic sequence composed of subtypes A, G, and E and regions of indeterminate classification, In particular, most of pol and tat/vpu, as well as the region encoding intracellular domain of gp41, did not cluster with any of the previously characterized HIV-1 subtypes, The clustering of the LTR of GR17 with subtype E was suggestive of a subtype E origin of the unclassified regions. However, the identification of distinct characteristics in the LTR, such as two functional NF-kappa B sites and a distinct TAR element, compared with those of circulating (A/E) recombinants, suggests that the partial subtype E sequences found in GR17 and the mosaic viruses (A/E) have not derived from each other, These results provide evidence that parental subtype E may have existed in the geographic area of Central Africa