1. Addition of zoledronic acid to neoadjuvant chemotherapy is not beneficial in patients with HER2-negative stage II/III breast cancer: 5-year survival analysis of the NEOZOTAC trial (BOOG 2010-01).
- Author
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de Groot S, Pijl H, Charehbili A, van de Ven S, Smit VTHBM, Meershoek-Klein Kranenbarg E, Heijns JB, van Warmerdam LJC, Kessels LW, Dercksen MW, Pepels MJAE, van Laarhoven HWM, Vriens BEPJ, Putter H, Fiocco M, Liefers GJ, van der Hoeven JJM, Nortier JWR, and Kroep JR
- Subjects
- Adult, Aged, Bone Density Conservation Agents administration & dosage, Breast Neoplasms metabolism, Breast Neoplasms pathology, Clinical Trials, Phase III as Topic, Female, Humans, Insulin blood, Insulin-Like Growth Factor I metabolism, Menopause, Middle Aged, Neoadjuvant Therapy, Receptor, ErbB-2 metabolism, Receptor, IGF Type 1 metabolism, Survival Analysis, Zoledronic Acid administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Density Conservation Agents therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms mortality, Zoledronic Acid therapeutic use
- Abstract
Background: Adjuvant bisphosphonates are associated with improved breast cancer survival in postmenopausal patients. Addition of zoledronic acid (ZA) to neoadjuvant chemotherapy did not improve pathological complete response in the phase III NEOZOTAC trial. Here we report the results of the secondary endpoints, disease-free survival, (DFS) and overall survival (OS)., Patients and Methods: Patients with HER2-negative, stage II/III breast cancer were randomized to receive the standard 6 cycles of neoadjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy with or without 4 mg intravenous (IV) ZA administered within 24 h of chemotherapy. This was repeated every 21 days for 6 cycles. Cox regression models were used to evaluate the effect of ZA and covariates on DFS and OS. Regression models were used to examine the association between insulin, glucose, insulin growth factor-1 (IGF-1) levels, and IGF-1 receptor (IGF-1R) expression with survival outcomes., Results: Two hundred forty-six women were eligible for inclusion. After a median follow-up of 6.4 years, OS for all patients was significantly worse for those who received ZA (HR 0.468, 95% CI 0.226-0.967, P = 0.040). DFS was not significantly different between the treatment arms (HR 0.656, 95% CI 0.371-1.160, P = 0.147). In a subgroup analysis of postmenopausal women, no significant difference in DFS or OS was found for those who received ZA compared with the control group (HR 0.464, 95% CI 0.176-1.222, P = 0.120; HR 0.539, 95% CI 0.228-1.273, P = 0.159, respectively). The subgroup analysis of premenopausal patients was not significantly different for DFS and OS ((HR 0.798, 95% CI 0.369-1.725, P = 0.565; HR 0.456, 95% CI 0.156-1.336, P = 0.152, respectively). Baseline IGF-1R expression was not significantly associated with DFS or OS. In a predefined additional study, lower serum levels of insulin were associated with improved DFS (HR 1.025, 95% CI 1.005-1.045, P = 0.014)., Conclusions: Our results suggest that ZA in combination with neoadjuvant chemotherapy was associated with a worse OS in breast cancer (both pre- and postmenopausal patients). However, in a subgroup analysis of postmenopausal patients, ZA treatment was not associated with DFS or OS. Also, DFS was not significantly different between both groups. IGF-1R expression in tumor tissue before and after neoadjuvant treatment did not predict survival., Trial Registration: ClinicalTrials.gov, NCT01099436 , April 2010.
- Published
- 2019
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