> The promise of bisphosphonates for breast cancer patients (March 2010)
Bisphosphonates are a group of drugs that help strengthen bones and are widely used to treat osteoporosis. In women with breast cancer that has spread to the bones, these drugs are part of standard care to help lower the risk of bone fractures and reduce bone pain.
Bisphosphonates may be given to women (both with and without cancer) who have, or are at high risk for, osteoporosis. Examples of common bisphosphonates are alendronate (Fosamax), ibandronate (Boniva) and risedronate (Actonel). Women may be at risk for osteoporosis simply due to older age or a loss of bone mineral density after menopause. Certain breast cancer treatments can also increase risk of osteoporosis. For example, chemotherapy can bring on early menopause and loss of bone density and aromatase inhibitors (a type of hormone therapy) can decrease bone mineral density. In these settings, bisphosphonates can help women improve their bone mineral density.
Cellular and animal studies have found that bisphosphonates may have some anti-tumor effects or may help chemotherapy kill more cancer cells. 2,3 Although data from human studies are limited, anti-tumor effects of bisphosphonates have also been found in studies of people with other types of cancer, such as multiple myeloma. 4 The possible anti-tumor effects of these drugs are now under study in women with breast cancer.
Early findings suggest bisphosphonates may lower the risk of breast cancer recurrence. A large clinical trial randomly assigned 1,803 premenopausal women with hormone receptor-positive early stage breast cancer to either hormone therapy alone or hormone therapy plus the intravenous bisphosphonate zoledronate (Zometa). 1 None of the women received chemotherapy. This study found that the use of zoledronate reduced the risk of breast cancer recurrence. 1 Women who took hormone therapy plus zoledronate had a 94.0 percent chance of survival without a recurrence (also called disease-free survival) after four years and women who took hormone therapy alone had a 90.8 percent chance of survival without a recurrence.1 Thus, use of zoledronate increased the chances of survival without a recurrence by 3.2 percent.
While these results are promising, not all prior studies have reached these conclusions. Further clinical trials are needed to confirm these results before bisphosphonates become a part of standard therapy for all women with early breast cancer. In addition, it is not known if zoledronate would be helpful in women who have had chemotherapy. However, according to Dr. Wendy Chen, a medical oncologist at the Dana Farber Cancer Institute, "Breast cancer survivors who are considering a medication for bone health (or to improve bone density) may want to choose a bisphosphonate instead of another type of medication.”
It is important to note that bisphosphonates have some serious risks. Although mostly a concern for those with metastatic breast cancer who take high doses, bisphosphonates can cause severe bone, joint and/or muscle pain. And, in rare cases, a serious jawbone disorder called osteonecrosis may occur.
Some oral bisphosphonates can irritate the esophagus. When taking these pills, a person should follow the directions carefully to prevent this side effect. They should be taken on an empty stomach with plenty of plain water while sitting or standing. Those taking the pills, should remain upright for at least 30 minutes and avoid eating, drinking or taking other medicines during this time.
- Gnant M, Mlineritsch B, Schippinger W, et al. for the ABCSG-12 Trial Investigators. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 360(7):679-91, 2009.
- Daubiné F, Le Gall C, Gasser J, Green J, Clézardin P. Antitumor effects of clinical dosing regimens of bisphosphonates in experimental breast cancer bone metastasis. J Natl Cancer Inst. 99(4):322-30, 2007.
- Brown HK, Holen I. Anti-tumour effects of bisphosphonates--what have we learned from in vivo models? Curr Cancer Drug Targets. 9(7):807-23, 2009.
- Avilés A, Nambo MJ, Neri N, Castañeda C, Cleto S, Huerta-Guzmán J. Antitumor effect of zoledronic acid in previously untreated patients with multiple myeloma. Med Oncol. 24(2):227-30, 2007.
- Gralow JR, Biermann JS, Farooki A, et al. NCCN Task Force report: Bone health in cancer care. J Natl Compr Canc Netw. 7 Suppl 3:S1-S32, 2009.