Link between Bisphosphonates and Breast Cancer
When breast cancer metastasizes, it often spreads first to the bones. Bone metastases can lead to complications such as pain, fractures, spinal cord compression, bone marrow suppression, and hypercalcemia. The primary reason for this link is that breast cancer cells stimulate bone cells called osteoclasts, and these osteoclasts in turn stimulate the growth of breast cancer cells.
Bisphosphonates have emerged as a highly effective therapeutic option for the prevention of skeletal complications secondary to bone metastases. They interrupt the relationship between osteoclasts and breast cancer cells in early stage breast cancer, slowing the progression of bone metastases while, at the same time, reducing the skeletal complications in women with metastatic breast cancer. Research has also demonstrated that bisphosphonates may prevent the development of bone metastases in newly diagnosed patients with no evidence of metastasis.
A number of agents are now approved in both Europe and the US. They included Clodronate, Pamidronate, Ibandronate, Zoledronic acid.
New and ongoing research
Lead researcher Gad Rennert, M.D., Ph.D., chairman of the Department of Community Medicine and Epidemiology at the Carmel Medical Center of Clalit Health Services and a faculty member at the Technion-Israel Institute of Technology in Israel, said these data help shed light on a possible new pathway for breast cancer prevention.
"We have identified a new class of drugs that is associated with a reduced risk of breast cancer, and if proven in randomized trials, we may be able to recommend it to postmenopausal women for this purpose," said Rennert.
Rennert and colleagues extracted data from the Breast Cancer in Northern Israel Study, which is a population-based, case-control study. They evaluated the use of bisphosphonates for at least five years in 4,575 postmenopausal study participants using a structured interview. The self-reported, long-term use of bisphosphonates prior to diagnosis was associated with a significant reduced relative risk for breast cancer by approximately 34%.
This reduction remained significant, at 29%, even after adjusting for a large variety of risk factors for breast cancer such as age, fruit and vegetable consumption, sports activity, family history of breast cancer, ethnic group, body mass index, calcium supplement and hormone replacement therapy use, number of pregnancies, months of breastfeeding and age at first pregnancy.
Moreover, the breast tumors identified among patients who used bisphosphonates were more often estrogen receptor positive and less often poorly differentiated.
"These tumors are the type that are associated with a better prognosis," said Rennert.
While most experts are cautiously optimistic about the results of this study, several of them said that more information is necessary, and as of now, they would not suggest the use of bisphosphonates for women who do not have osteoporosis.
For more information:
- Coleman RE. Bisphosphonates in breast cancer. Ann Oncol 2005 May;16(5):687-95. Epub 2005 Mar 31.
- Logman JF, Heeg BM, Botteman MF, Kaura S, van Hout BA. Economic evaluation of zoledronic acid for the prevention of osteoporotic fractures in postmenopausal women with early-stage breast cancer receiving aromatase inhibitors in the UK. Ann Oncol. 2009 Dec 2. [Epub ahead of print]
- Ghazi M, Roux C. Hormonal deprivation therapy-induced osteoporosis in postmenopausal women with breast cancer. Best Pract Res Clin Rheumatol. 2009 Dec;23(6):805-11.
- Theriault RL. Bisphosphonates: ready for use as adjuvant therapy of breast cancer? Curr Opin Obstet Gynecol. 2009 Nov 19. [Epub ahead of print]
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