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Predictors of increased risk for early treatment non-adherence to oral anti-estrogen therapies in early-stage breast cancer patients

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Abstract

Purpose

Non-adherence to the oral anti-estrogen therapies (AET) tamoxifen and aromatase inhibitors in early-stage hormone receptor-positive breast cancer is associated with numerous negative clinical outcomes. Prior studies have identified that non-adherence is associated with psychological and menopause-related factors which are present during AET, but the presence of these characteristics prior to AET initiation has not been investigated.

Methods

Psychological and menopause symptoms (depression, generalized anxiety, insomnia, somatosensory amplification, hot flash frequency, and hot flash-related interference) were assessed pre-AET initiation as predictors of subsequent non-adherence in 73 participants (Mage = 55.0, SD = 10.1 years). Participants self-reported treatment adherence after three and 6 weeks on AET. Participants who did not initiate treatment were excluded from the analysis.

Results

Discriminant function analyses revealed that the hypothesized set of psychological and menopause symptoms at baseline (pre-AET) together statistically distinguished between those who were non-adherent (n = 19; 26.0%) from adherent (n = 54; 74.0%) at 6 weeks. Model classification accuracy was statistically significant (Wilks’ ƛ = 0.782, χ2(6) = 15.50, p = 0.017) at the 6-week timepoint. Results were consistent at 3 weeks. Pre-AET psychological and menopause symptoms correctly classified 6-week treatment adherence 77.9% of the time. Depression contributed most to distinguishing between adherers and non-adherers.

Conclusions

The presence of a composite profile of psychological and menopause symptoms prior to AET initiation may help to identify early treatment non-adherence. Results can be used to identify patients at risk for non-adherence and to guide psychological and symptom management interventions.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

AET:

Anti-estrogen therapies

DFA:

Discriminant Function Analysis

GAD-7:

Generalized Anxiety Disorder

HFRDIS:

Hot Flash-Related Daily Interference Scale

ISI:

Insomnia Severity Index

PHQ-8:

Patient Health Questionnaire

SSAS:

Somatosensory Amplification

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Acknowledgements

This work was conducted with support from the Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL 1TR002541) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, and its affiliated academic healthcare centers, or the National Institutes of Health. This research was supported by the Brigham and Women’s Hospital Department of Psychiatry and the Dana-Farber Cancer Institute Department of Psychosocial Oncology and Palliative Care Research Fellowship.

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Author notes

  1. Miryam Yusufov and Margo Nathan have contributed equally as joint first author.

Authors and Affiliations

  1. Department of Psychosocial Oncology & Palliative Care, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA

    Miryam Yusufov & Hadine Joffe

  2. Women’s Hormones and Aging Research Program, Department of Psychiatry, Brigham & Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Margo Nathan, Aleta Wiley, Julia Russell & Hadine Joffe

  3. Department of Psychiatry, Harvard Medical School Brigham and Women’s Hospital, 75 Francis Street, Thorn 1111, Boston, MA, 02215, USA

    Miryam Yusufov, Margo Nathan & Hadine Joffe

  4. Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA

    Ann Partridge

  5. Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA

    Ann Partridge

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  1. Miryam Yusufov
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Contributions

All authors contributed to the study conception and design. Data analysis was performed by MY and AW. The first draft of the manuscript was written by MY and MN and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hadine Joffe.

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Conflict of interest

Dr. Miryam Yusufov reports in the past 12 months: Consultant: Blue Note Therapeutics. Dr. Hadine Joffe reports in past 12 months: Consultant/Advisory Board: NeRRe/KaNDy, Sojournix, Eisai. Grant/Research Support: National Institutes of Health, Merck, NeRRe/KaNDy, Pfizer, QUE Oncology. Spouse: Merck Research Lab—employee; Arsenal Biosciences—consulting and equity, Tango—equity.

Ethical approval

All participants provided written informed consent for study procedures, which were approved by the Institutional Review Board of Dana-Farber/Harvard Cancer Center (Protocol # 14-206).

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Informed consent was obtained from all individual participants included in the study.

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Yusufov, M., Nathan, M., Wiley, A. et al. Predictors of increased risk for early treatment non-adherence to oral anti-estrogen therapies in early-stage breast cancer patients. Breast Cancer Res Treat 185, 53–62 (2021). https://doi.org/10.1007/s10549-020-05920-y

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