Abstract

Abstract Background: The bone modifying agents (BMAs), bisphosphonates, reduce risk of cancer recurrence after diagnosis of early-stage breast cancer (EBC), particularly in postmenopausal women, while another BMA, denosumab, has not been shown to improve EBC outcomes. The 2017 American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) clinical guidelines recommended consideration of adjuvant bisphosphonates for postmenopausal women with EBC who are candidates for adjuvant systemic therapy. Despite this, small survey-based studies suggest that their prescribing is variable. The goal of this study was to evaluate prescribing of adjuvant BMAs in the United States before and after publication of the 2017 ASCO/CCO guidelines (ACGD). Methods: This retrospective cohort study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database and included 11,740 patients diagnosed with stage I-III breast cancer from 2012 to 2019. We analyzed data on use of BMAs (bisphosphonates or denosumab) in the adjuvant setting, defined as receiving first dose of BMA within 24 months of breast cancer diagnosis and before diagnosis of metastatic disease. Any episodes of BMA use after a metastatic recurrence were excluded. We used Chi-squared test to compare the proportion of patients receiving adjuvant BMAs pre- and post-ACGD. We used univariable and multivariable logistic regression analyses with list-wise missing value deletions to identify predictors of adjuvant BMA prescribing. Results: Of 11,740 patients, 7,391 were diagnosed pre-ACGD and 4,349 post-ACGD. Of the pre-ACGD patients, 545 (7.4%) patients received adjuvant BMAs, and of the post-ACGD patients, 390 (9.0%) patients received adjuvant BMAs. Patients diagnosed post-ACGD were more likely to receive adjuvant BMAs compared with patients diagnosed pre-ACGD (OR 1.23; 95% confidence interval (CI) 1.08-1.42; p=0.002). Of patients age ≥ 50 (n=9,654), 522 of 6,027 (8.7%) and 360 of 3,627 (9.9%) received adjuvant BMAs pre- and post-ACGD, respectively (OR 1.146; 95% CI 0.996-1.319; p=0.0572). In multivariable analysis, age ≥ 50 years at diagnosis, post-menopausal status, having T2 or higher stage at diagnosis, adjuvant endocrine therapy, and coexisting bone loss diagnosis were significantly associated with receipt of adjuvant BMAs (Table 1). Of the 935 patients who received adjuvant BMAs, 615 (65.8%) had denosumab only, 305 (32.6%) had a bisphosphonate only, and 13 (1.4%) received both a bisphosphonate and denosumab during the course of adjuvant treatment. Two patients received an adjuvant BMA as part of a clinical trial. Conclusions: Adjuvant BMA prescribing in our cohort was overall low; there was a modest increase in uptake in patients with EBC diagnosed after the publication of the 2017 ACGD. Older age, higher T stage, endocrine therapy, and coexisting bone loss diagnoses were significantly associated with receipt of adjuvant BMAs. Despite the recommendations for bisphosphonates in the adjuvant setting in EBC, the majority of patients received denosumab only. Considering these findings, further research is required to determine barriers to BMA prescribing and factors that influence physician and patient decisions. There continues to be a need for improved implementation and dissemination of recent guidelines, including the updated 2021 ASCO/CCO recommendations which continue to endorse bisphosphonate use in the adjuvant setting. Table 1: Univariable and multivariable logistic regression analyses to identify predictors of receiving adjuvant BMAs sabs Citation Format: Nicole Odzer, Rachel Jaber Chehayeb, Maryam Lustberg, Cary P. Gross, Julia Foldi. Patterns of adjuvant bone modifying agent use in patients with early-stage breast cancer in the United States [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-02-05.

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