Factors Influencing Tamoxifen Adherence in Women With Breast Cancer Receiving Tamoxifen in Botswana.

Breast cancer (BC) is the second-most common cancer in women in sub-Saharan Africa (SSA) (Black 2019, Trimble 2017). Tamoxifen forms a cornerstone for treatment of ER+ breast cancer and daily use after initial medical, surgical, and/or radiation therapy decreases the annual odds of recurrence and death by 39% and 31% respectively (EBCTCG 2005). Despite the proven benefits of tamoxifen, non-adherence is common. Previous reports have indicated that 31-50% of women do not adhere to prescribed treatment regimens (Lash 2006, Lambert 2018, Peddie 2021). The reasons for non-adherence are broad and not fully understood but are thought to be influenced by numerous factors including medication side-effects, beliefs about cancer, and social support framework (Clancy 2020). Data is extremely limited concerning the adherence rates to tamoxifen therapy in Africa.

The metabolism of tamoxifen is complex. It is metabolized to its effector/active metabolites via the cytochrome P450 (CYP) enzyme system, principally CYP2D6 with CYP2B6 playing a lesser, but important role (Nthontho Keneuoe Cecilia 2022). The CYP2D6 gene is highly variable but four principal drug metabolizer phenotypes have been identified: poor, intermediate, extensive, and ultra-rapid metabolizers (Nthontho KC 2022). Reduced speed of tamoxifen metabolism in poor metabolizers has been associated with higher risk of treatment failure, due to increased drug level in vivo and subsequent increased tamoxifen related side effects (Nardin 2020). However, to date, these various phenotypes have not been evaluated in an African population, so it is unclear to what extent these phenotypes effect tamoxifen adherence in SSA.

A unique aspect among the breast cancer population in Botswana is that a large portion of these women are also living with HIV. Studies have shown that the prevalence of HIV in the general population is up to 17.6% (Bhatia 2019). Little is known how antiretroviral medications effect tamoxifen adherence. One particular Anti Retroviral Therapy (ART) medication, efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor and potent CYP-inducer is used by a large portion of WLW HIV in SSA (Maseng 2022). EFV has been shown in vitro to increase estrogen expression both by inducing growth in ER-positive breast cancer cells lines (Sikora 2010) and clinically due to the development of gynecomastia seen in male patients (Osman 2020). It remains unclear, however, if and to what extent the combined administration of tamoxifen and efavirenz contributes to reduced tamoxifen adherence.