Highlights
- •Optimal adjuvant bisphosphonate dose and duration in breast cancer is unclear.
- •We evaluated outcomes of early treatment cessation in the ABCSG-12 dataset.
- •Receiving fewer than 7 zoledronate infusions had no significant effect on DFS or OS.
- •Adjuvant bisphosphonate de-escalation in breast cancer must be further studied.
Abstract
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.
Keywords
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Article info
Publication history
Published online: December 31, 2022
Accepted:
December 3,
2022
Received in revised form:
November 30,
2022
Received:
October 31,
2022
Identification
Copyright
Crown Copyright © 2022 Published by Elsevier Ltd. All rights reserved.
