Immediate zoledronic acid use combined with endocrine therapy reduces recurrence and increases survival in postmenopausal early breast cancer patients

Recent clinical trials suggest potential anticancer activity for bisphosphonates combined with adjuvant endocrine therapy in patients with hormone receptor-positive (HR+) early breast cancer. In the ZO-FAST study, researchers previously demonstrated that adding zoledronic acid to adjuvant therapy significantly improved bone mineral density and prolonged disease-free survival (DFS) compared to delayed zoledronic acid. At this years’s CTRC-AACR San Antonio Breast Cancer Symposium, Richard de Boer, MD (Royal Melbourne Hospital, Victoria, Australia) reported the long-term data from ZO-FAST.

In the ZO-FAST study, de Boer and colleagues explored the addition of zoledronic acid to adjuvant endocrine therapy to reduce bone mineral density loss seen with the use of aromatase inhibitors. In the study, 1,065 postmenopausal women with HR+ early breast cancer receiving letrozole were randomized to receive immediate zoledronic acid every six months or to a delayed group where zoledronic acid was started at a later time only if the patient experienced a fracture or a documented fall in bone mineral density.

After 60 months of follow-up, immediate zoledronic acid significantly decreased the bone mineral density loss in both the lumbar spine and in the hip (p 0.0001 for both). “Furthermore,” de Boer said, “the secondary endpoint of the study was also met as patients immediately treated with zoledronicacid arm had a 34% decrease in the risk of disease recurrence compared with patients in the delayed zoledronic acid arm (p= 0.0375).” Researchers also conducted an exploratory subgroup analysis based on menopausal status at the time of breast cancer diagnosis. Data indicated that in women who were truly menopausal at diagnosis (N=888), immediate treatment with zoledronic acid reduced the risk for disease recurrence by 29% and improved overall survival by 35%. In addition, patients in the delayed group, who did not start with zoledronic acid but who switched to start at a later time (N=144), also appeared to benefit from the zoledronic acid with an improvement in disease outcomes compared with those women who never started the bisphosphonate.

With respect to safety, de Boer focussed on the incidence of osteonecrosis of the jaw (ONJ), a serious complication that has previously been associated with the use of zoledronic acid. After 5 years of follow-up, only 3 confirmed cases were reported in ZO-FAST (0,56%). This low incidence of ONJ underlines the safety of zoledronic acid use in this setting.

In conclusion, the 60 month follow-up of the ZO-FAST trial confirms that the addition of zoledronic acid to adjuvant endocrine therapy increased bone mineral density and reduces the risk for disease recurrence in postmenopausal women with early hormone receptor-positive breast cancer.

Speaker Richard de Boer


Richard de Boer, MD
Royal Melbourne Hospital, Melbourne, Victoria, Australia

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