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Polypharmacy, over-the-counter medications, and aromatase inhibitor adherence in early-stage breast cancer

  • Clinical trial
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Polypharmacy is associated with negative health outcomes and decreased medication adherence. Polypharmacy is common in cancer populations, but few studies have evaluated the relationship between polypharmacy and aromatase inhibitor (AI) adherence. No studies have evaluated the relationship between over-the-counter (OTC) supplements and AI adherence. Our primary hypothesis was that polypharmacy would be associated with increased risk of premature AI discontinuation.

Methods

This exploratory analysis used data from the Exemestane and Letrozole Pharmacogenetics (ELPh) trial, a prospective, multicenter, randomized controlled trial that enrolled participants from 2005 to 2009. Included patients were female, postmenopausal, with stage 0–III breast cancer, who had completed indicated chemotherapy, surgery, and radiation. Participants were randomized to adjuvant exemestane or letrozole and completed serial clinical examinations and questionnaires for two years. Concomitant medication data were collected prospectively. Cox proportion models were used for statistical analysis of the relationship between polypharmacy, OTCs, medication class, and AI adherence.

Results

In the 490 analyzed participants, use of any prescription medications at baseline was associated with decreased risk of premature AI discontinuation (HR 0.56, p = 0.02). Use of selective serotonin reuptake inhibitors (SSRIs) or selective serotonin and norepinephrine reuptake inhibitors (SNRIs) at baseline was associated with decreased risk of premature AI discontinuation (HR 0.67, p = 0.04). Use of any OTCs was not associated with AI discontinuation.

Conclusion

Baseline use of prescription medications but not OTCs was associated with increased AI persistence. Future research is needed to understand how this can be utilized to promote AI adherence.

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Data availability

The data analyzed in this study are available from the corresponding author on reasonable request.

Abbreviations

AI:

Aromatase inhibitor

AIMSS:

Aromatase inhibitor-associated musculoskeletal symptoms

BCPT:

Breast Cancer Prevention Trial

BMI:

Body mass index

CESD:

Center for Epidemiological Studies Depression

ELPh:

Exemestane and Letrozole Pharmacogenetics

ET:

Endocrine therapy

HADS-A:

Hospital Anxiety and Depression Scale-Anxiety

OTC:

Over the counter

PRO:

Patient-reported outcomes

PSQI:

Pittsburgh Sleep Quality Index

SSRI:

Selective serotonin reuptake inhibitor

SNRI:

Selective serotonin and norepinephrine reuptake inhibitor

VAS:

Visual analog scale

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Funding

The ELPh trial (ClinicalTrials.gov number: NCT00228956) was supported by a Pharmacogenetics Research Network Grant Number U01 GM61373 (DAF) and Clinical Pharmacology training grants 5T32 GM08425 (DAF) from the National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MD and from grants from Pfizer, Inc. (DFH), Novartis Pharma AG (DFH), and Fashion Footwear Association of New York/QVC Presents Shoes on SaleTM (DFH). The National Center for Research Resources (NCRR) provided grants M01-RR000042 (UM), M01-RR00750 (IU), and M01-RR00052 (JHU). Letrozole and exemestane were provided to study participants by Novartis and Pfizer, respectively. NLH is supported by R01 CA266012 from the National Cancer Institute, National Institutes of Health, Bethesda, MD.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA

    Elizabeth Joyce, Daniel F. Hayes & N. Lynn Henry

  2. Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, USA

    Xueting Tao & Kelley M. Kidwell

  3. Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, USA

    Vered Stearns

  4. Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, USA

    Anna Maria Storniolo

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  1. Elizabeth Joyce
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Contributions

AMS, DFH, NLH, and VS were responsible for design and conduct of the ELPh clinical trial. EJ and NLH contributed to study conception and design. Data collection, analysis, and preparation were performed by EJ, XT, KMK, and NLH. The first draft of the manuscript was written by EJ and NLH. All authors read and commented on all prior versions of the manuscript. All authors approved the final manuscript.

Corresponding author

Correspondence to N. Lynn Henry.

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Competing interests

VS has received research grants to her institution from Abbvie, Biocept, Novartis, Pfizer, Puma Biotechnology, and QUE Oncology, she has been a member of the Novartis Advisory Board since October 2021, and she is the Chair of a Data Safety Monitoring Board with AstraZeneca. She additionally has non-financial support with the Foundation Medicine Study Assays. As noted above, DFH reports receiving grants through his institution from the manufacturers of letrozole (Novartis) and exemestane (Pfizer). DFH reports support unrelated to this study but provided to his institution in the last 24 months during conduct and analysis of this study from AstraZeneca, Menarini Silicon Biosystems, Merrimack Pharmaceuticals, and Pfizer. DFH reports personal income related to consulting or advisory board activities from Arvenis, BioVeca, BioTheranostics a Hologic Company, Cellworks, Centrix, Cepheid, EPIC Sciences, EXACT Sciences, Freenome, Guardant, L-Nutra, Macrogenics, Oncocyte, Predictus BioSciences, Stratipath, Tempus, Turnstone Biologics, and Xilis. The University of Michigan holds a patent for which DFH is the named investigator and which was licensed to Menarini Silicon Biosystems, from whom UM and DFH received annual royalties ending 1/1/2022. DFH reports personally held stock options from InBiomotion, Xilis, and from CellWorks. NLH is a consultant for Myovant Pharmaceuticals, a steering committee member for AstraZeneca, and receives royalties from Up-To-Date. The other authors had no disclosures to report.

Ethical approval

The ELPh study received approval from each of the three participating sites: Indiana University Bren and Melvin Simon Cancer Center, the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, and the University of Michigan Comprehensive Cancer Center.

Consent to participate

Informed consent was obtained from all individuals included in the ELPh study for participation and publication.

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Joyce, E., Tao, X., Stearns, V. et al. Polypharmacy, over-the-counter medications, and aromatase inhibitor adherence in early-stage breast cancer. Breast Cancer Res Treat 204, 539–546 (2024). https://doi.org/10.1007/s10549-023-07218-1

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  • DOI: https://doi.org/10.1007/s10549-023-07218-1

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