Effective inhibition of aromatase inhibitor‐associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole

Abstract

Although standard clinical prognostic factors predict outcome in diffuse large B‐cell lymphoma (DLBCL), predicting the outcome of patients might be further refined using biological factors. We tested whether serum cytokines could provide prognostic information in DLBCL patients. Thirty cytokines were measured in pretreatment samples from newly diagnosed DLBCL patients using a multiplex ELISA. Sixty‐nine patients treated with R‐CHOP plus epratuzumab were used in an initial cohort and 185 patients treated with standard R‐CHOP served as a subsequent validation cohort. In the initial cohort, elevated serum interleukin‐10 [IL‐10; hazard ratio (HR) = 6.6, P = 0.022], granulocyte macrophage colony‐stimulating factor (HR = 10.8, P= 0.027) and IP‐10 (interferon‐inducible protein‐10, CXCL10; HR = 3.32, P = 0.015) were associated with event‐free survival (EFS). An identical analysis of the subsequent validation cohort confirmed that elevated serum levels of IP‐10 were strongly associated with a poor EFS (HR = 2.42, P = 0.0007); and also identified interleukin‐8 (IL‐8; HR = 3.40, P = 0.00002) and interleukin‐2 receptor (IL‐2R, CD25; HR = 2.59, P = 0.0012) as significantly associated with prognosis. The prognostic significance of elevated IP‐10 remained significant after adjustment for the International Prognostic Index (EFS − HR 1.99, P = 0.009, overall survival‐HR 1.93, P = 0.021). Elevated pretreatment serum IP‐10 levels are therefore associated with an increased likelihood of disease relapse and an inferior survival in patients with DLBCL. Am. J. Hematol. © 2012 Wiley Periodicals, Inc.

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

“…While most women will have normal BMD, routine screening may identify women who are at increased risk for bone loss and are candidates for bisphosphonate therapy [16]. Randomized clinical trials such as the Zometa-Femara Adjuvant Synergy Trial (Z-FAST in the United States and ZO-FAST in Europe) support the use of zoledronic acid (4 mg), a bisphosphonate, every 6 months to prevent AI-associated bone loss [17,18]. In addition to calcium and vitamin D supplementation, any patient who is starting AI therapy and has a T-score \ -2.0 should receive zoledronic acid (4 mg) twice yearly [19].…”

Zoledronic acid use in cancer patients

“…72 Zoledronic acid has demonstrated efficacy in preventing CTIBL and improving bone mineral density (BMD) above baseline in premenopausal and postmenopausal women with early BC who are receiving adjuvant endocrine therapy. [73][74][75][76][77][78][79] In addition to its bone-protective benefits, recent large, phase 3 studies demonstrated that ZOL can prolong DFS compared with standard therapy alone. 14,16,80 Completed Trials and Interim Reports The Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 12 (ABCSG-12) is a large, randomized, phase 3 trial that compared the efficacy of endocrine therapy with and without ZOL in 1803 premenopausal women with early stage BC.…”

Final 5‐year results of Z‐FAST trial

“…2,12 In addition, zoledronic acid has been shown to increase bone mineral density (BMD) in premenopausal and postmenopausal breast cancer patients at risk of cancer treatment-induced bone loss. 2,3,[13][14][15][16][17] Recently, preclinical and clinical data have also demonstrated anticancer effects of bisphosphonates in breast and other cancer types. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] The prevention and treatment of bone loss with upfront (initiated simultaneously with letrozole) versus delayed (initiated with a decrease in T score to <À2 or occurrence of clinical nontraumatic fracture) zoledronic acid in early breast cancer patients receiving letrozole was evaluated in 3 similarly designed, geographically diverse studies (Z-FAST; ZO-FAST; E-ZO-FAST) and in the similarly-designed N03CC study.…”

“…15 Interim (<36 months follow-up) results from the former 3 studies indicate that upfront rather than delayed-start zoledronic acid is significantly more effective in preventing bone loss. 2,3,13,14 This article reports the final, 5-year results of the Z-FAST study.…”