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The impact of HIV on non-adherence for tamoxifen among women with breast cancer in South Africa

  • Epidemiology
  • Published:
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Abstract

Purpose

Women living with HIV (WLWH) and breast cancer (BC) have worse overall survival than HIV-negative women with BC, and poor adherence to prescribed tamoxifen is known to contribute to poor survival. We therefore investigated the association of HIV infection with adherence to adjuvant tamoxifen among women with localized hormone receptor (HR)-positive breast cancer in South Africa.

Methods

Among 4,097 women diagnosed with breast cancer at six hospitals in the prospective South African Breast Cancer and HIV Outcomes (SABCHO) cohort study between July 2015 and December 2020, we focused on black women with stages I-III HR-positive breast cancer who were prescribed 20 mg of adjuvant tamoxifen daily. We collected venous blood once from each participant during a routine clinic visit, and analyzed concentrations of tamoxifen and its metabolites using a triple quadruple mass spectrometer. We defined non-adherence as a tamoxifen level < 60 ng/mL after 3 months of daily tamoxifen use. We compared tamoxifen-related side effects, and concurrent medication use among women with and without HIV and developed multivariable logistic regression models of tamoxifen non-adherence.

Results

Among 369 subjects, 78 (21.1%) were WLWH and 291 (78.9%) were HIV-negative. After a median (interquartile range) time of 13.0 (6.2–25.2) months since tamoxifen initiation, the tamoxifen serum concentration ranged between 1.54 and 943.0 ng/mL and 208 (56.4%) women were non-adherent to tamoxifen. Women < 40 years of age were more likely to be non-adherent than women > 60 years (73.4% vs 52.6%, odds ratio (OR) = 2.49, 95% confidence interval (CI) = 1.26–4.94); likewise, WLWH (70.5% vs 52.6%, OR = 2.16, 95% CI = 1.26–3.70) than HIV-negative women. In an adjusted model WLWH had twice the odds of non-adherence to tamoxifen, compared to HIV-negative women (OR = 2.40, 95% CI = 1.11–5.20).

Conclusion

High rates of non-adherence to adjuvant tamoxifen may limit the overall survival of black South African women with HR-positive breast cancer, especially among WLWH.

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the women who participated in this study. We also thank the dedicated team of study research assistants for their assistance with the study.

Funding

NIH/R01-CA19262701 and R01-CA250012, The South African Medical Research Council/ University of the Witwatersrand Common Epithelial Cancer Research Center (MRC/WITS CECRC), The South African Medical Research Council, Pharmacogenomics in Precision Medicine (MRC-RFA-SHIP 01–2019) award entitled “Understanding the pharmacogenetic and pharmacokinetic basis of tamoxifen (TAM) treatment-failure for breast cancer in black African women”, MRC UK, Cancer Research and Global Health: Pump-Priming Call entitled “Molecular Genetics of Lobular Breast Cancer in a South African cohort and effect of HIV infection” DSO is a K12 Scholar supported by the National Cancer Institute of the National Institutes of Health under Award Number K12CA226330. The funders had no role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The Wits Health Consortium (PTY) Ltd provided support in the form of payroll administration of salaries from grant funds for authors OA and MJ but did not have any additional role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Strengthening Oncology Services Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Wenlong Carl Chen, Nivashni Murugan, Rofhiwa Mathiba & Maureen Joffe

  2. MRC South Africa and the University of the Witwatersrand Centre for Common Epithelial Cancers Research Unit, Johannesburg, South Africa

    Oluwatosin A. Ayeni, Paul Ruff & Maureen Joffe

  3. Soweto Comprehensive Cancer Centre, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa

    Oluwatosin A. Ayeni, Rofhiwa Mathiba & Paul Ruff

  4. Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Shingirai Chiwambutsa, Wenlong Carl Chen & Collen Masimirembwa

  5. National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa

    Wenlong Carl Chen

  6. Department of Pharmaceutical Medicine, African Institute of Biomedical Science and Technology Block C Wilkins Hospital, Harare, Zimbabwe

    Nyasha Kapungu, Comfort Kanji, Roslyn Thelingwani & Collen Masimirembwa

  7. Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Nivashni Murugan, Boitumelo Phakathi, Sarah Nietz & Herbert Cubasch

  8. Department of Radiation Oncology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Duvern Ramiah

  9. Sylvester Comprehensive Cancer Center and Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA

    Daniel S. O’Neil

  10. Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Judith S. Jacobson & Alfred I. Neugut

  11. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA

    Judith S. Jacobson & Alfred I. Neugut

  12. School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, 27 St Andrews Road, Parktown, Johannesburg, 2193, South Africa

    Tobias Chirwa

  13. Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Alfred I. Neugut

Authors
  1. Oluwatosin A. Ayeni
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  2. Shingirai Chiwambutsa
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Contributions

Conceptualization and design: OAA, MJ, CM, HC, PR, and AIN Acquisition of data: OAA, NM, RM, BP, SN, DR, PR, and HC Bioanalysis of tamoxifen: NK, CK, RT, and CM Formal analysis: OAA, SC, and TC Interpretation of result: OAA, SC, DSO, TC, JSJ, CM, and AIN Funding acquisition: DSO, JSJ, PR, HC, MJ, CM, and AIN Project administration: OAA, WCC, MJ, HC, and CM Software: OAA and TC Validation: OAA, MJ, TC, CM, and AIN Writing—original draft: OAA and AIN Writing—review & editing: All Authors We also thank our funders: National Institutes of Health, The South African Medical Research Council, Medical Research Council (MRC) UK Cancer Research and Global Health, National Cancer Institute of the National Institutes of Health.

Corresponding author

Correspondence to Oluwatosin A. Ayeni.

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Competing interests

AIN has consulted for Otsuka, Eisai, GlaxoSmithKline, United biosource Corp, Hospira. He has support from Otsuka. He is on the medical advisory board of EHE Intl. All other authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the University of the Witwatersrand Human Research Ethics Committee, and the Institutional Review Board of Columbia University in New York, NY.

Consent to participate

All women provided written or fingerprint-confirmed informed consent. The study was performed in accordance with the Declaration of Helsinki.

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Ayeni, O.A., Chiwambutsa, S., Chen, W.C. et al. The impact of HIV on non-adherence for tamoxifen among women with breast cancer in South Africa. Breast Cancer Res Treat 197, 647–659 (2023). https://doi.org/10.1007/s10549-022-06835-6

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