Clinical trial NCT06660030: Factors Influencing Tamoxifen Adherence in Women With Breast Cancer Receiving Tamoxifen in Botswana.
Official title: Factors Influencing Tamoxifen Adherence in Women With Breast Cancer Receiving Tamoxifen in Botswana.
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Breast Cancer Female
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2024-10-26
Enrollment: 128
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will include females with ER+ breast cancer who are \>18 years of age. The study population will include both women living with and without HIV.

Patients offered questionnaires and blood draws will only include women treated as outpatients and be of sufficient mental capacity to personally consent to the study.

Brief summary: Botswana is an ideal location to investigate tamoxifen adherence for numerous reasons. First, in contrast to many other countries in SSA, tamoxifen is affordable and widely available to women with ER+ breast cancer in Botswana. There is also a sufficiently high prevalence of WLW HIV and breast cancer in Botswana to provide adequate power for the proposed study. Lastly, there is a well-developed medical and scientific infrastructure, both from the clinical and laboratory perspective, to allow for successful completion of this proposed study

Detailed description: 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.

Eligibility criteria: Inclusion Criteria.

* All women over the age of 18, taking (or have taken) tamoxifen for treatment of ER+ breast cancer and being HIV positive
* All women over the age of 18, taking (or have taken) tamoxifen for treatment of ER+ breast cancer and being HIV negative

Exclusion Criteria:

* Males
* Women with ER negative breast cancer
* Women under 18 years of age at time of study administration.

Primary outcomes:
measure: Primary outcome
timeFrame: 12 months
Secondary outcomes:
measure: Secondary outcome
timeFrame: 12 months
Other outcomes:
Locations:
city: Gaborone
country: Botswana
facility: Princess Marina Hospital
Study officials:
References: