Management of Cancer-Treatment–Induced Bone Loss in Postmenopausal Women Undergoing Adjuvant Breast Cancer Therapy: A Z-FAST Update
Section snippets
Aromatase Inhibitors as Adjuvant Therapy
Four phase III randomized trials compared the safety and efficacy of the third-generation AIs with tamoxifen or placebo as adjuvant or extended adjuvant therapy in postmenopausal women with breast cancer.
The randomized, double-blind Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial evaluated the effectiveness of anastrozole alone, tamoxifen alone, or anastrozole plus tamoxifen as adjuvant therapy for localized breast cancer in postmenopausal women.8, 12, 13, 14 The combination treatment
Strategies to Counteract Bone Loss During Adjuvant Treatment With AIs
Bisphosphonates are an important class of drugs that act by inhibiting osteoclastic bone resorption.10 Oral bisphosphonates are widely used in the treatment of postmenopausal osteoporosis. Nitrogen-containing oral bisphosphonates (eg, alendronate, risedronate) have been shown to increase BMD and decrease fracture occurrence in women with established postmenopausal osteoporosis.20 Long-term patient compliance, however, may be limited by gastrointestinal intolerance that in turn limits optimal
Z-FAST Results
Z-FAST is a randomized, open-label, multicenter trial designed to compare the safety and efficacy of upfront versus delayed zoledronic acid treatment in preventing CTIBL in postmenopausal women with hormone-receptor–positive breast cancer who are also receiving adjuvant therapy with letrozole. Accrual was completed in December 2003, with 602 patients enrolled at 93 sites in the United States and Canada.22 The companion ZO-FAST study has completed accrual of more than 1,000 patients at 112
Conclusion
The prevention of CTIBL in long-term adjuvant breast cancer therapy is a high priority. Changes in BMD during such therapy in postmenopausal women can be easily monitored and addressed with the coadministration of zoledronic acid. The Z-FAST results show that combining the anticancer efficacy of letrozole with the bone-protective effect of zoledronic acid is an effective way to prevent CTIBL.
Upfront zoledronic acid was shown to prevent CTIBL in postmenopausal women receiving adjuvant letrozole
References (24)
- et al.
Zoledronic acid inhibits cancer treatment-induced bone loss in premenopausal patients with breast cancer who are receiving adjuvant endocrine treatment
Breast
(2005) Optimizing bisphosphonate therapy in patients with breast cancer on endocrine therapy
Semin Oncol
(2004)Switching trial of adjuvant tamoxifen with an aromatase inhibitor in postmenopausal patients with breast cancer
Clin Breast Cancer
(2004)- et al.
Switching of postmenopausal women with endocrine responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifencombined results of ABCSG trial 8 and ARNO 95 trial
Lancet
(2005) - et al.
Zoledronic acid in the prevention of cancer treatment-induced bone loss in postmenopausal women receiving letrozole as adjuvant therapy for early breast cancer
Breast
(2005) Long-term implications of bone loss in breast cancer
Breast
(2004)- et al.
Osteoporosis due to cancer treatmentPathogenesis and management
J Clin Oncol
(2000) - et al.
Skeletal health in postmenopausal survivors of early breast cancer
Int J Cancer
(2005) - et al.
American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancerStatus report 2004
J Clin Oncol
(2005) - et al.
A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer
N Engl J Med
(2004)
A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer
N Engl J Med
Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancerResults of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses
Cancer
Cited by (54)
Link between estrogen deficiency osteoporosis and susceptibility to bone metastases: A way towards precision medicine in cancer patients
2018, BreastCitation Excerpt :Thirdly, another key field includes the side-effects on reproductive hormones of several treatments used for the management of cancer patients [6]. Particularly, hormonal-ablative treatments in women with hormone receptor-positive cancers lead to a rapid increase in bone resorption [7,8]. Reproductive hormones play a key role in normal bone remodeling maintenance, and estrogen deprivation in women with breast cancer will lead to accelerated bone loss and increased risk of osteoporosis (OP), with related fractures that have a significant negative impact on the life of cancer patients [9].
Antiresorptive therapies in oncology and their effects on cancer progression
2012, Cancer Treatment ReviewsDosing of zoledronic acid throughout the treatment continuum in breast cancer
2011, Critical Reviews in Oncology/HematologyCitation Excerpt :Moreover, because most nitrogen-containing BPs showed promising antitumor and antimetastatic activities in vitro [73], an evolving goal of recent trials was to evaluate the activity of BPs for preventing bone metastasis and improving overall clinical outcomes including disease-free and recurrence-free survival (DFS and RFS, respectively). Recent data from phase III trials support twice-yearly ZOL dosing to preserve BMD during adjuvant endocrine therapy in the early breast cancer setting (stage I to IIIa) [53–56]. In the 3 companion studies Z-FAST (N = 602), ZO-FAST (N = 1065), and E-ZO-FAST (N = 523), upfront ZOL (4 mg q6mo) prevented AIBL and improved BMD versus baseline in postmenopausal women receiving adjuvant letrozole therapy [75–78].
Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial
2011, Annals of OncologyCitation Excerpt :The latest results from the main ATAC trial and bone sub-protocol show that, on completion of anastrozole treatment, fragility fracture rates decrease back to levels similar to those observed with tamoxifen, and fractures occurring after treatment completion are not associated with patients becoming osteoporotic after AI treatment. Overall, the prevention of CTIBL in long-term adjuvant AI breast cancer therapy remains a high priority [25]. What these study results demonstrate is that, in contrast to the beneficial effects of anastrozole on breast cancer recurrence which extend substantially beyond the cessation of treatment [14], anastrozole-associated BMD loss begins to resolve immediately after treatment cessation and any bone loss associated with anastrozole can be monitored and managed as needed [25–29].
Aromatase Inhibitors and Their Side Effects: What Hand Surgeons Should Know
2010, Journal of Hand Surgery
- 1
Dr Brufsky has received research grant support and honoraria from Novartis.