TY - JOUR
T1 - Does the number of 6-monthly adjuvant zoledronate infusions received affect treatment efficacy for early breast cancer?
T2 - A sub-study of ABCSG-12
AU - Beltran-Bless, Ana-Alicia
AU - Clemons, Mark J
AU - Fesl, Christian
AU - Greil, Richard
AU - Pond, Gregory R
AU - Balic, Marija
AU - Vandermeer, Lisa
AU - Bjelic-Radisic, Vesna
AU - Singer, Christian F
AU - Steger, Guenther G
AU - Helfgott, Ruth
AU - Egle, Daniel
AU - Sölkner, Lidija
AU - Gampenrieder, Simon Peter
AU - Kacerovsky-Strobl, Stephanie
AU - Suppan, Christoph
AU - Ritter, Magdalena
AU - Rinnerthaler, Gabriel
AU - Pfeiler, Georg
AU - Fohler, Hannes
AU - Hlauschek, Dominik
AU - Hilton, John
AU - Gnant, Michael
N1 - Lehr-KH Ordensklinikum Linz;
Gampenrieder, Greil: Salzburg Cancer Research Institute; 3d Medical Department, Paracelsus Medical University Salzburg; Cancer Cluster Salzburg, Austria, Rinnerthaler: Ontario Clinical Oncology Group, Department of Oncology, McMaster University, Hamilton, Ontario, Canada
PY - 2023/2
Y1 - 2023/2
N2 - BACKGROUND: The widespread adoption of adjuvant bisphosphonate therapy for postmenopausal early breast cancer (EBC) patients was based on results of the Early Breast Cancer Trialist Group (EBCTCG) meta-analysis. Despite multiple regimens evaluated, there was no signal of varying efficacy with type, dose/dose intensity of bisphosphonate administration. We evaluated the effect of early treatment cessation using long-term outcome data from the ABCSG-12 trial.PATIENTS AND METHODS: ABCSG-12 randomized 1803 hormone-receptor positive EBC patients on ovarian suppression between 1999 and 2006 to receive 4 mg zoledronic acid 6-monthly or not (and tamoxifen or anastrozole, 2:2 factorial design). In the current study, we evaluated whether the number of zoledronate infusions had an impact on breast cancer-specific outcomes. We hypothesized that amongst patients who received at least one zoledronate infusion, the number of infusions had no effect on outcomes. Time-to-event endpoints were analysed with Cox models and Kaplan Meier curves starting from a 3-year landmark. BMD analysis was restricted to patients who participated in the BMD sub-study.RESULTS: 725 patients who received at least one zoledronate infusion were included in the time-to-event analysis. There was no statistically significant difference in disease-free or overall survival in the patients who received ≤6 zoledronate infusions (n = 170) compared to those who received ≥7 zoledronate infusions (n = 555).CONCLUSIONS: Comparable to efforts to de-escalate treatment duration in metastatic bone disease, there was no evidence to indicate that a reduced number of zoledronate infusions is associated with reduced adjuvant efficacy. Further studies to define optimal regimens of adjuvant bone-targeted therapies are required.
AB - BACKGROUND: The widespread adoption of adjuvant bisphosphonate therapy for postmenopausal early breast cancer (EBC) patients was based on results of the Early Breast Cancer Trialist Group (EBCTCG) meta-analysis. Despite multiple regimens evaluated, there was no signal of varying efficacy with type, dose/dose intensity of bisphosphonate administration. We evaluated the effect of early treatment cessation using long-term outcome data from the ABCSG-12 trial.PATIENTS AND METHODS: ABCSG-12 randomized 1803 hormone-receptor positive EBC patients on ovarian suppression between 1999 and 2006 to receive 4 mg zoledronic acid 6-monthly or not (and tamoxifen or anastrozole, 2:2 factorial design). In the current study, we evaluated whether the number of zoledronate infusions had an impact on breast cancer-specific outcomes. We hypothesized that amongst patients who received at least one zoledronate infusion, the number of infusions had no effect on outcomes. Time-to-event endpoints were analysed with Cox models and Kaplan Meier curves starting from a 3-year landmark. BMD analysis was restricted to patients who participated in the BMD sub-study.RESULTS: 725 patients who received at least one zoledronate infusion were included in the time-to-event analysis. There was no statistically significant difference in disease-free or overall survival in the patients who received ≤6 zoledronate infusions (n = 170) compared to those who received ≥7 zoledronate infusions (n = 555).CONCLUSIONS: Comparable to efforts to de-escalate treatment duration in metastatic bone disease, there was no evidence to indicate that a reduced number of zoledronate infusions is associated with reduced adjuvant efficacy. Further studies to define optimal regimens of adjuvant bone-targeted therapies are required.
KW - Female
KW - Humans
KW - Adjuvants, Immunologic/therapeutic use
KW - Breast Neoplasms/pathology
KW - Chemotherapy, Adjuvant
KW - Diphosphonates
KW - Treatment Outcome
KW - Zoledronic Acid/therapeutic use
U2 - 10.1016/j.ejca.2022.12.003
DO - 10.1016/j.ejca.2022.12.003
M3 - Original Article (Journal)
C2 - 36592505
SN - 0959-8049
VL - 180
SP - 108
EP - 116
JO - EUROPEAN JOURNAL OF CANCER
JF - EUROPEAN JOURNAL OF CANCER
ER -