The protective effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole: 36-month follow-up.

Abstract

e11111 Background: Adjuvant treatment with aromatase inhibitors (AIs) in postmenopausal women (PMW) with early breast cancer (EBC) can be associated with bone loss. Update of BIG-98 suggests that sequential TAM and Letrozole (LET) have similar efficacy to 5 years of LET. This study evaluates whether addition of zoledronic acid (ZOL) to LET, switched from TAM, can prevent bone loss. Methods: This is an open-label, randomized phase II study of PMW with hormone receptor positive EBC previously treated with TAM for 2.5 years, with bone mineral density (BMD) T-score ≥ -2.5. Patients were randomly assigned to receive 2.5mg/day LET +/- ZOL. Patients on treatment arm receive 5 intravenous administrations of 4 mg ZOL every 6 months. All patients are evaluated with blood chemistry and BMD test every 6 months in the first 3 years and yearly in the next 2 years. All patients receive vitamin D and calcium supplements. A comparison between groups and between time points was performed by one-way ANOVA with repeated measures using the Mixed model. Results: Eighty nine patients have been randomized. Median age was 58.9 years (46.5-83.6). Eighty six patients were evaluable (3 screening failure); 39 were randomized to receive ZOL and 47 to the control group. Median follow-up was 41.4 months (range 3.4-60). Change over time in lumbar spine T-score was significantly different between the ZOL and control groups, (P=0.0013). In the control group a significant decline in lumbar BMD was noticed (P=0.0031), whereas in the ZOL group there was no significant change in BMD over time (P= 0.10). No significant differences between groups and time points were found. With regards to other parameters, no interaction between groups and time trends were observed. The most common adverse event with ZOL was a mild, transient flu-like syndrome within 2 days of administration. No serious renal adverse events or osteonecrosis of jaw (ONJ) were reported. Conclusions: Sequential TAM and AIs in the adjuvant setting of EBC in PMW can be associated with decreased BMD. In our study, LET-induced bone loss increases with time, though a significant benefit in BMD was seen when ZOL was added to LET.