Clodronate.

Two early observations about the first generation bisphosphonate, clodronate, suggested that it would likely have clinical utility; specifically, it was a more potent anti-resorptive but a less potent inhibitor of mineralisation than its predecessor etidronate. The known mechanism of action differs from that of the later nitrogen-containing bisphosphonates, as clodronate is metabolised intracellularly to a toxic analog of adenosine triphosphate, AppCCl2p, which causes mitochondrial dysfunction, impaired cellular energy metabolism and osteoclast apoptosis. For pre-clinical studies in a variety of disease models, liposomal clodronate has become the agent of choice for macrophage depletion, for example in a recent study to enhance haematopoietic chimerism and donor-specific skin allograft tolerance in a mouse model.

Poor Prognosis After Second Locoregional Recurrences in the CALOR Trial.

Background: Isolated locoregional recurrences (ILRRs) of breast cancer confer a significant risk for the development of distant metastasis. Management practices and second ILRR events in the Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial were investigated.

Methods: In this study, 162 patients with ILRR were randomly assigned to receive postoperative chemotherapy or no chemotherapy.

Body Mass Index at Diagnosis and Breast Cancer Survival Prognosis in Clinical Trial Populations from NRG Oncology/NSABP B-30, B-31, B-34, and B-38.

Background: Body mass index (BMI) has been associated with breast cancer outcomes. However, few studies used clinical trial settings where treatments and outcomes are consistently evaluated and documented. There are also limited data assessing how patient/disease characteristics and treatment may alter the BMI-breast cancer association.

The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer.

Background: Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases.

Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial.

Background: Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients.

Methods: The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins.

Lost in transition? Thoughts on retirement--"will you still need me, will you still feed me, when i'm sixty-four?".

Oncologists should plan for a future beyond full-time oncology, but there is little practical guidance for a successful transition into retirement. This paper provides strategies for various aspects of retirement planning and transitioning. More prospective information is needed.

Bone Health in Patients with Breast Cancer: Recommendations from an Evidence-Based Canadian Guideline.

Bone loss is common in patients with breast cancer. Bone modifying agents (BMAs), such as bisphosphonates and denosumab, have been shown to reverse or stabilize bone loss and may be useful in the primary and metastatic settings. The purpose of this review is to provide clear evidence-based strategies for the management of bone loss and its symptoms in breast cancer.

Bone-related complications and quality of life in advanced breast cancer: results from a randomized phase III trial of denosumab versus zoledronic acid.

Purpose: Denosumab was shown to be superior to zoledronic acid in preventing skeletal related events (SRE) in patients with breast cancer and bone metastases in a randomized, double-blind phase III study. We evaluated further results from this study related to skeletal complications and health-related quality of life (HRQoL).

Experimental Design: Patients were randomized 1:1 to receive subcutaneous denosumab 120 mg (n = 1,026) and intravenous placebo, or intravenous zoledronic acid 4 mg (n = 1,020) and subcutaneous placebo every 4 weeks.

REO-001: A phase I trial of percutaneous intralesional administration of reovirus type 3 dearing (Reolysin®) in patients with advanced solid tumors.

Purpose: This open-labeled, phase I clinical trial was designed to determine the safety and tolerability of percutaneous intralesional administration of wild-type oncolytic revovirus type 3 Dearing (Reolysin®) in cancer patients with accessible and evaluable disease, who had otherwise failed to improve on standard cancer interventions.

Experimental Design: An escalating dose of Reolysin® starting from up to 10(10) plague forming units (PFU) was administered to each cohort of three patients per dose level. Viral shedding, reovirus neutralizing antibody response, toxicity and clinical response were assessed.

Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial.

Background: Bisphosphonates are thought to act through the osteoclast by changing bone microenvironment. Previous findings of adjuvant clodronate trials in different populations with operable breast cancer have been mixed. The National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-34 aims to ascertain whether oral clodronate can improve outcomes in women with primary breast cancer.

Controlling angiogenesis in breast cancer: a systematic review of anti-angiogenic trials.

Purpose: Angiogenesis is critical for tumor growth and a promising therapeutic target. This review will summarize and analyze data from clinical trials of anti-angiogenic agents in the treatment of breast cancer (BC).

Design: A systematic search of PubMed and conference databases was performed to identify reports of randomized clinical trials investigating specific anti-angiogenic agents in the treatment of BC.

Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy.

Purpose: Denosumab, a fully human monoclonal antibody to RANKL, suppresses bone resorption. This study evaluated the effects of denosumab in i.v.

Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases.

Purpose: Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor-kappaB ligand, suppresses bone resorption. In this study, we evaluated the efficacy and safety of five dosing regimens of denosumab in patients with breast cancer-related bone metastases not previously treated with intravenous bisphosphonates (IV BPs).

Patients And Methods: Eligible women (n = 255) with breast cancer-related bone metastases were stratified by type of antineoplastic therapy received and randomly assigned to one of six cohorts (five denosumab cohorts [blinded to dose and frequency]; one open-label IV BP cohort).

The role of bisphosphonates in early breast cancer.

Clinical trials are investigating the use of bisphosphonates in patients with early (nonmetastatic) breast cancer. Results from trials of clodronate are generally encouraging but somewhat contradictory. Of the three trials published to date, two reported that clodronate had beneficial effects on both bone metastases and survival.

Evaluating bone mass and bone quality in patients with breast cancer.

Bone remodeling is a process by which bone renews itself focally in distinct areas on cancellous (ie, trabecular) bone and/or in the Haversian systems of cortical (or compact) bone. Normal bone turnover involves the ordered metabolism of bone-resorbing cells (osteoclasts) and bone-forming cells (osteoblasts). Estrogen exerts a multitude of actions on bone tissues and is integral to bone health, and estrogen deprivation leads to accelerated bone loss.