Bisphosphonates are medicines used to prevent or treat osteoporosis. They do this by limiting the activity of certain bone cells, called osteoclasts, which help cause the bone weakening and breakdown that leads to osteoporosis.
Bisphosphonates also may help stop breast cancer from spreading to the bones by making it harder for breast cancer cells to grow in bones. So doctors wondered if certain bisphosphonates would help reduce the risk of recurrence (the cancer coming back) in women diagnosed with early-stage breast cancer. Reclast (chemical name: zoledronic acid), Zometa (chemical name: zoledronic acid), Boniva (chemical name: ibandronate), and Bonefos (chemical name: clodronate) are the bisphosphonates studied to reduce breast cancer recurrence risk.
But until December 2013, results from studies had been mixed. Some research found that bisphosphonates helped reduce risk, while other studies showed that they didn’t reduce risk.
A large study has found that bisphosphonates do reduce the risk of recurrence, but only in postmenopausal women or women who have been made postmenopausal through ovarian suppression.
The study, “Effects of bisphosphonate treatment on recurrence and cause-specific mortality in women with early breast cancer: A meta-analysis of individual patient data from randomized trials,” was presented on Dec. 12, 2013 at the 2013 San Antonio Breast Cancer Symposium.
This study was a meta-analysis -- a study that combines and analyzes the results of many earlier studies. In this case, the results of nearly 18,000 women in 41 studies were analyzed. The earlier studies looked at women diagnosed with early-stage breast cancer. After surgery, the women were randomly assigned to receive a bisphosphonate or not.
Looking at ALL women in the study – both pre- and postmenopausal:
- distant breast cancer recurrence was 1.1% lower in women receiving a bisphosphonate (distant recurrence is when breast cancer comes back in a part of the body away from the breast)
- recurrence in the bones was 1.5% lower in women receiving a bisphosphonate
Looking at just postmenopausal women in the study:
- distant breast cancer recurrence was 3.5% lower in women receiving a bisphosphonate
- deaths from breast cancer were 3.1% lower in women receiving a bisphosphonate
Both of these differences were significant, which means they were likely because of the bisphosphonate treatment and not just due to chance.
The cancer’s estrogen-receptor status, number of lymph nodes involved, and type of chemotherapy given after surgery didn’t affect the bisphosphonates’ ability to lower risk in postmenopausal women.
The researchers found that bisphosphonates didn’t reduce the risk of breast cancer coming back in the other breast (contralateral breast cancer). This means that bisphosphonates probably wouldn’t reduce the risk of breast cancer in women who’ve never been diagnosed, so they wouldn’t be used as a preventive medicine.
Importantly, the researchers said that oral bisphosphonates (pills taken by mouth) likely wouldn’t reduce recurrence risk. Bisphosphonates given intravenously once or twice a year are the best for reducing the risk of recurrence in postmenopausal women. Zometa, Boniva, Bonefos, and Reclast are bisphosphonates that are given intravenously. Bonefos is not commercially available in the United States, but is available in Canada and Europe.
It’s also important to know that while this research shows that bisphosphonates reduce distant recurrence risk in postmenopausal women, it doesn’t say anything about reducing risk in women who are diagnosed with breast cancer before menopause and become postmenopausal during treatment. (Because hormonal therapy is taken for 5 or 10 years, it’s possible that many premenopausal women may become postmenopausal while they’re taking hormonal therapy.) So it’s not yet clear if these women would benefit from taking a bisphosphonate. More research is needed.
Bisphosphonates may cause rare but serious side effects. Research has shown that bisphosphonates can increase the risk of atypical femur fractions when taken for 5 years or longer. The femur is the large leg bone that runs from your hip to your knee. An atypical fracture means that the bone is broken in an unusual spot. Still, atypical femur fractures are rare -- only about 0.22% of women taking a bisphosphonate for more than 5 years will have an atypical femur fracture.
The bisphosphonates also can sometimes cause another rare but serious side effect, osteonecrosis of the jaw, a condition in which the cells in the jawbone start to die. Researchers think that osteonecrosis of the jaw may develop because bisphosphonates stop the body from repairing microscopic damage to the jawbone that can happen during routine dental procedures or from every day wear and tear. But it's still not clear why this happens in some people and not in others. If you’re taking a bisphosphonate, tell your dentist right away. Together, you can work out a dental treatment schedule that keeps your teeth healthy and minimizes your risk of osteonecrosis of the jaw.
If you’re a postmenopausal woman who’s been diagnosed with early-stage breast cancer, you may want to ask your doctor if an intravenous bisphosphonate makes sense for you to reduce your risk of distant recurrence. You may already be considering a bisphosphonate to strengthen your bones or treat osteoporosis. If so, it may make sense to opt for an intravenous bisphosphonate that also can help reduce recurrence risk.
For more information on bisphosphonates, visit the Bisphosphonates for Osteoporosis and Bone Protection in the Breastcancer.org Bone Health section.