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

Oluwatosin A Ayeni^{1

2}, Shingirai Chiwambutsa³, Wenlong Carl Chen^{4

3

5}, Nyasha Kapungu⁶, Comfort Kanji⁶, Roslyn Thelingwani⁶, Nivashni Murugan^{4

7}, Rofhiwa Mathiba^{4

8}, Boitumelo Phakathi⁷, Sarah Nietz⁷, Duvern Ramiah⁹, Daniel S O'Neil¹⁰, Judith S Jacobson^{11

12}, Paul Ruff^{13

8}, Herbert Cubasch⁷, Tobias Chirwa¹⁴, Maureen Joffe^{4

13}, Collen Masimirembwa^{3

6}, Alfred I Neugut^{11

12

15}

Affiliations

¹ MRC South Africa and the University of the Witwatersrand Centre for Common Epithelial Cancers Research Unit, Johannesburg, South Africa. Oayeni@witshealth.co.za.
² Soweto Comprehensive Cancer Centre, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa. Oayeni@witshealth.co.za.
³ Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁴ Strengthening Oncology Services Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁵ National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa.
⁶ Department of Pharmaceutical Medicine, African Institute of Biomedical Science and Technology Block C Wilkins Hospital, Harare, Zimbabwe.
⁷ Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁸ Soweto Comprehensive Cancer Centre, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.
⁹ Department of Radiation Oncology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁰ Sylvester Comprehensive Cancer Center and Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA.
¹¹ Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
¹² Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹³ MRC South Africa and the University of the Witwatersrand Centre for Common Epithelial Cancers Research Unit, Johannesburg, South Africa.
¹⁴ School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, 27 St Andrews Road, Parktown, Johannesburg, 2193, South Africa.
¹⁵ Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

PMID: 36538247
PMCID: PMC10149344
DOI: 10.1007/s10549-022-06835-6

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

Oluwatosin A Ayeni et al. Breast Cancer Res Treat. 2023 Feb.

. 2023 Feb;197(3):647-659.

doi: 10.1007/s10549-022-06835-6. Epub 2022 Dec 20.

Authors

Affiliations

¹ MRC South Africa and the University of the Witwatersrand Centre for Common Epithelial Cancers Research Unit, Johannesburg, South Africa. Oayeni@witshealth.co.za.
² Soweto Comprehensive Cancer Centre, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa. Oayeni@witshealth.co.za.
³ Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁴ Strengthening Oncology Services Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁵ National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa.
⁶ Department of Pharmaceutical Medicine, African Institute of Biomedical Science and Technology Block C Wilkins Hospital, Harare, Zimbabwe.
⁷ Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁸ Soweto Comprehensive Cancer Centre, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.
⁹ Department of Radiation Oncology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁰ Sylvester Comprehensive Cancer Center and Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA.
¹¹ Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
¹² Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹³ MRC South Africa and the University of the Witwatersrand Centre for Common Epithelial Cancers Research Unit, Johannesburg, South Africa.
¹⁴ School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, 27 St Andrews Road, Parktown, Johannesburg, 2193, South Africa.
¹⁵ Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

PMID: 36538247
PMCID: PMC10149344
DOI: 10.1007/s10549-022-06835-6

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.

Keywords: Breast cancer; HIV; Non-adherence; Tamoxifen.

PubMed Disclaimer

Conflict of interest statement

AIN has consulted for Otsuka, Eisai, GlaxoSmith-Kline, 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.

Figures

**Fig. 1**
The reported side effects of tamoxifen use, overall and by HIV status among women with breast cancer

See this image and copyright information in PMC

Comment in

Pharmacogenetics: uncovering the complex relationship between HIV and non-adherence among South African breast cancer patients treated with tamoxifen.
Nthontho KC, Tawe L, Paganotti GM. Nthontho KC, et al. Breast Cancer Res Treat. 2023 Jun;199(2):399-400. doi: 10.1007/s10549-023-06913-3. Epub 2023 Mar 30. Breast Cancer Res Treat. 2023. PMID: 36997749 No abstract available.

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

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

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