Effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole

Abstract

599 Background: Adjuvant treatment with aromatase inhibitors (AIs) in postmenopausal women (PMW) with early breast cancer (EBC) can be associated with decreased bone mineral density (BMD) and increased risk of osteoporosis and fractures. Tamoxifen (TAM) has bone protective effect. BIG 1–98 recent, 71 months update suggests that sequential therapy of TAM and letrozole (LET) in either order, have similar efficacy to 5 years of LET. This study is designed to evaluate the efficacy and safety of zoledronic acid (ZA) in preventing AIs bone loss after 2.5 years of TAM. Methods: This is an open-label, randomized phase II study of PMW with hormone receptor positive EBC previously treated with TAM for the last 2.5 years (with BMD T score ≥ -2.5). Patients are randomly assigned to receive LET (2.5mg/ daily) ± ZA. Patients on treatment arm receive 4 mg IV ZA every 6 months for 2 years. All patients are being evaluated every 6 (0–36) months with blood chemistry and BMD test. All patients receive vitamin D and calcium supplement. A comparison between groups and between time points is performed by one-way ANOVA with repeated measures using the Mixed model. Results: Seventy four patients were screened. Median age was 58.9 years (46.5–83.6). All patients are alive, one had an ipsilateral recurrence. Seventy two patients were evaluable (2 were screening failure), 33 randomized to receive ZA and 39 to the control group. Median follow-up (FU) was 18.2 months (1–47). At this point in time a significant interaction between groups and time trend was found, in favor of ZA treated group in lumbar T score (p = 0.0055). While in the control group a significant decline in lumbar BMD was noticed (p = 0.008), in the treatment group BMD did not change over time (p = 0.2971). Adverse events with ZA were mild with some flue like syndrome. No serious renal adverse event or ONJ (osteonecrosis of jaw) cases were reported. ZA was safe and well tolerated. Conclusions: Sequential adjuvant treatment with TAM and AIs in PMW with EBC can be associated with decreased BMD and increased risk of osteoporosis. In our study, LET-induced bone loss increases with time. A significant benefit in BMD was seen when ZA was added to LET. A longer follow up is needed to evaluate the real magnitude of ZA protective effects. [Table: see text]