Bone Health and Breast Cancer
Posted 6/7/2010
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There has been a great deal of interest in the interplay between bone health and breast cancer (risk of getting it in the first place, risk of recurrence, and then pace of progression). The bottom line is that healthier, stronger bones are helpful in all three situations. Here is a nice summary from Oncology Stat:
The 2009 San Antonio Breast Cancer Symposium:Potentially Practice-Changing Studies
2010 Jan 25, Lee Schwartzberg, MD, Editor-in-Chief
2010 Jan 25, Lee Schwartzberg, MD, Editor-in-Chief
Bone health and breast cancerThe skeleton is the most common site of metastasis from breast cancer. In recent years, the molecular interplay between breast cancer cells and the osseous stroma has been extensively studied and is now well understood. A complex feedback loop including elaborated bone cytokines can drive tumor growth, which, in turn, releases factors leading to osteoclast activation. The bisphosphonates are a group of drugs that interfere with osteoclast action and have been clinically utilized for many years in metastatic breast cancer to reduce skeletal-related events (SREs) such as pathologic fractures, need for radiation therapy, or surgery. The most potent bisphosphonate, the nitrogencontaining zoledronic acid, is proven to reduce SREs in breast cancer and osseous metastasis from other cancers. It is delivered as a monthly IV infusion. More recently, a new class of agents has been developed showing promising activity against metastatic bone cancer. Denosumab is a first-in-class monoclonal antibody that inhibits RANK-ligand, a key factor in mediating osteoclast activity. Stupeck et al presented results of a double-blind, randomized, controlled trial comparing denosumab with zoledronic acid for the prevention of SREs in patients with bone metastases who had not been previously exposed to IV bisphosphonates.
Of 2000 patients enrolled, one-third had prior SREs; the median duration of the presence of bone metastases was 2 months. Compared with zoledronic acid, denosumab reduced the risk of the first SRE by 18%, the median time to first radiation by 26%, and the median time to first bone pain by 13%; all of these differences were statistically significant. The overall skeletal morbidity rate for patients receiving denosumab was reduced by 22% compared with the rate for those treated with zoledronic acid. There was no difference in the rate of disease progression.Adverse events were similar in both groups, except for the incidence of renal toxicity, which was 8.5% in the zoledronic acid group vs 4.9% in the denosumab group. Acute-phase reactions occurred in 27.3% of patients receiving zoledronic acid but in 10.4% receiving denosumab. Osteonecrosis of the jaw was seen in both groups, at a 2% occurrence rate with denosumab and 1.4% with zoledronic acid.
These encouraging results support the use of denosumab as a new standard of supportive therapy in the metastaticsetting.
2Bisphosphonates remain of intense interest in early-stage breast cancer because of accumulating evidence that their adjuvant usage could reduce the development of skeletal metastases and perhaps even improve DFS. A recent publication by the Austrian Breast Cancer Study Group in The New England Journal of Medicine, reporting on a clinical trial investigating hormonal therapy with or without bisphosphonates in premenopausal women, supported this concept.
Oral bisphosphonates are widely used by postmenopausal women who are at risk for, or who are already experiencing, osteoporosis. Some data in the past have also suggested that oral bisphosphonates may reduce the risk of breast cancer.At San Antonio 2009, Rowan Chlebowski and colleagues presented provocative results from the Women's Health Initiative, a huge lifestyle intervention trial involving postmenopausal women.
As part of this study, baseline oral bisphosphonate use was recorded; it was present in a small fraction of patients. These women differed from the main population in a number of other baseline factors, such as body mass index (lower), Gail model risk level (higher), and various other factors, which were all accounted for in a multivariate statistical analysis performed by the authors. The incidence of invasive breast cancer was reduced in the women who used bisphosphonates by one-third, although the incidence of in-situ breast cancer was increased. Most of the reduction was in the group with invasive ER+ tumors. No difference in stage or grade was noted. Along with the evidence that intravenous bisphosphonates may improve DFS in both premenopausal and postmenopausal women, the results suggested that bisphosphonates may have an effect on the developmental pathway of invasive breast cancer. More direct, prospective data will, of course, be required to establish or refute this hypothesis. Nonetheless, the evidence is accumulating on the benefit of bisphosphonates in altering breast cancer occurrence and recurrence.
2010 Jan 25, Lee Schwartzberg, MD, Editor-in-Chief
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