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)

Autor: Jacobus J M van der Hoeven, Saskia van de Ven, Hein Putter, Gerrit-Jan Liefers, Marta Fiocco, Judith R. Kroep, LW Kessels, A. Charehbili, Johan W. R. Nortier, Birgit E.P.J. Vriens, Elma Meershoek-Klein Kranenbarg, Joan B. Heijns, M. Wouter Dercksen, Vincent T.H.B.M. Smit, Stefanie de Groot, Hanno Pijl, MJ Pepels, Hanneke W. M. van Laarhoven, Laurence J. C. van Warmerdam
Přispěvatelé: Oncology, AGEM - Re-generation and cancer of the digestive system, CCA - Cancer Treatment and Quality of Life
Rok vydání: 2019
Předmět:
Oncology
Cancer Research
Survival
Receptor
ErbB-2
medicine.medical_treatment
Receptor
IGF Type 1
Breast cancer
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Insulin
Insulin-Like Growth Factor I
Non-U.S. Gov't
Bone Density Conservation Agents
Research Support
Non-U.S. Gov't
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Neoadjuvant Therapy
Docetaxel
030220 oncology & carcinogenesis
Female
Menopause
Research Article
Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
medicine.drug
Adult
medicine.medical_specialty
Cyclophosphamide
Breast Neoplasms
Subgroup analysis
Research Support
lcsh:RC254-282
Neoadjuvant chemotherapy
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
Internal medicine
Journal Article
medicine
Humans
Zoledronic acid
Survival analysis
Aged
Chemotherapy
Proportional hazards model
business.industry
medicine.disease
Survival Analysis
Clinical Trials
Phase III as Topic
business
IGF-1R
Zdroj: Breast Cancer Research, 21(1)
Breast Cancer Research, 21, 1
Breast Cancer Research, Vol 21, Iss 1, Pp 1-9 (2019)
Breast cancer research, 21(1):97. BioMed Central
Breast Cancer Research, 21
Breast Cancer Research : BCR
Breast Cancer Research, 21(1). BioMed Central
ISSN: 1465-542X
1465-5411
DOI: 10.1186/s13058-019-1180-6
Popis: 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.
Databáze: OpenAIRE
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