The addition of zoledronic acid to adjuvant endocrine therapy increased bone mineral density and reduced the risk for disease recurrence among postmenopausal women with early hormone receptor-positive breast cancer, according to new data from the ZO-FAST trial.

Richard de Boer, M.D., of the Royal Melbourne Hospital in Victoria, Australia, presented long-term data from the Zometa-Femara Adjuvant Synergy Trial (ZO-FAST) at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

De Boer and colleagues explored adding zoledronic acid, an intravenous bisphosphonate, to adjuvant endocrine therapy to reduce bone mineral density loss seen with aromatase inhibitors and to improve survival outcomes.

When he presented initial data from ZO-FAST at the 2010 CTRC-AACR San Antonio Breast Cancer Symposium, de Boer indicated that early zoledronic acid resulted in a significantly improved bone mineral density and an improved disease-free survival. At this year’s symposium, he reported long-term data and data on the effect of menopausal status at breast cancer diagnosis on disease-free survival.

Researchers randomly assigned 1,065 patients who were about to commence letrozole, an aromatase inhibitor, 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, “the primary endpoint of the trial was successfully achieved — up-front zoledronic acid significantly decreased bone mineral density loss in both the lumbar spine and the hip,” de Boer said. “The secondary endpoint of an improvement in disease-free survival was also met with a 34 percent decrease in disease recurrence in the patients receiving the up-front zoledronic acid.”

Researchers 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, immediate treatment with zoledronic acid reduced the risk for disease recurrence by 29 percent and improved overall survival by 35 percent.

“In addition, patients in the delayed group, who did not start with zoledronic acid but who switched to start at a later time, also appeared to benefit from the zoledronic acid with an improvement in disease outcomes compared with those women who never started the bisphosphonate,” de Boer said.

Additional studies are needed to fully define the patient populations most likely to benefit from adjuvant zoledronic acid in this setting.

Until then, “patients with hormone receptor-positive breast cancer who are postmenopausal and about to commence letrozole have the option of considering the addition of zoledronic acid — primarily to maintain bone mineral density but also with the aim of reducing the risk for disease recurrence,” de Boer said.

Source: AACR