Researchers found that postmenopausal women who started taking zoledronic acid when they began treatment with the aromatase inhibitor letrozole saw improved bone strength in the spine and hip compared with women who started zoledronic acid after their bone density dropped too low.
The same study showed that those who started treatment with zoledronic acid earlier saw fewer local and distant breast cancer recurrences than their peers who began treatment later.
Aromatase inhibitors like letrozole (Femara) are standard-of-care treatments for postmenopausal women with hormone-sensitive breast cancer. However, they have been linked to bone weakness, which can lead to a higher risk of fractures and osteoporosis.
Bisphosphonates like zoledronic acid (Zometa) are bone-strengthening medicines that some doctors prescribe to help prevent the bone loss that aromatase inhibitors may cause. In past studies, researchers explored whether bisphosphonates might also have anticancer benefits, but findings varied.
In the ZO-FAST trial, researchers studied the use of zoledronic acid over 5 years to see if it more effectively prevented bone weakness when started early or after bone loss occurred. They also analyzed its impact on time to recurrence, or disease-free survival (DFS), in specific subgroups of participants.
The 1,065 women enrolled in this study were postmenopausal and had estrogen or progesterone receptor-positive, stage I, II or IIIA breast cancer. They had normal or slightly below-normal bone density compared with healthy peers, but not osteoporosis, a condition in which bone density is so low the risk of fracture rises. No one had been treated with letrozole, other hormonal therapies or bisphosphonates in the past.
The women were randomly assigned to two treatment arms (groups). All participants took a daily 2.5mg letrozole pill for 5 years, along with daily calcium and vitamin D. In the first, immediate-start group, women began treatment with 4 mg of zoledronic acid within 1 month of the trial start date and continued treatment every 6 months for 5 years. Women assigned to a second, delayed-start group began the same treatment only after they had a fracture or their bone density tested too low.
For this study, researchers considered bone density low if a woman's T-score fell below -2. A normal density T-score usually measures -1.0 or higher.
After 5 years of treatment, results showed that women who started treatment with zoledronic acid immediately had 34 percent less risk of DFS, as well as fewer local and distant recurrences, than women who started after they had bone issues. Yet, there was no impact on overall survival in either group.
- 27 percent of women in the delayed-start group began zoledronic acid treatment because of decreases in bone density
- bone strength in the spine and hip improved more in the immediate-start group than in the delayed-start group
- women over 60 or who had been menopausal for 5 or more years at the start of treatment saw more improvement in bone strength than women who were recently menopausal
What This Means For You
The ZO-FAST study suggests that zoledronic acid is an important part of maintaining or improving bone strength in women with early-stage breast cancer, especially because bones may be weakened by other breast cancer treatments.
The finding that zoledronic acid may improve disease-free survival supports results from other trials, such as AZURE. These trials suggest that specific groups of women may have better breast cancer outcomes when taking zoledronic acid alongside other treatments, particularly women who have been menopausal for 5 or more years. More research needs to be done on the timing of the start of menopause and treatment with zoledronic acid, as well as on the medicine’s interaction with other aromatase inhibitors.
If you are interested in treatment with zoledronic acid and its potential impact on DFS, talk with your doctor about these findings and your eligibility for future clinical trials.
Coleman, R, de Boer, R, Eidtmann, H, et al. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Annals of Oncology; 2013; 24(2):398-405.