CYP2D6 Genotypes and Breast Cancer Clinical Outcomes in the Indonesian Population

Study Overview
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Brief Summary
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The utilization of tamoxifen is considerably high in Indonesia, with about 170,000 tamoxifen prescriptions filed in 2015. It is metabolized by the enzyme CYP2D6, resulting in its active metabolite, endoxifen, which has been proven to be effective in the prevention and treatment of breast cancer. Studies showed the CYP2D6 gene has more than 100 variants; some of which are linked with reduced drug activity, while others do not have any pathological implications. The metabolizer profile of these variants is generally grouped into Ultra-rapid, Normal, Intermediate, and Poor Metabolizers (UM, NM, IM, and PM, respectively). In our previous study (NCT04312347), the investigators recruited 150 breast cancer patients who were taking adjusted dose of tamoxifen daily based on their CYP2D6 phenotype. Although the investigators have measured the endoxifen level of the patients with adjusted treatment, the clinical outcomes of the study are not yet conclusive.

Official Title
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CYP2D6 Genotypes and Breast Cancer Clinical Outcomes in the Indonesian Population (Pengaruh Genotipe CYP2D6 Terhadap Efektivitas Penggunaan Tamoksifen Untuk Pasien Kanker Payudara ER+ Pada Populasi Indonesia)

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Tamoxifen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female diagnosed with ER+ breast cancer have been genotyped and classified as PM and IM in the previous study are recommended by doctor to take tamoxifen 40 mg according to their metabolizer profile have finished the definitive therapy course (surgery, chemotherapy, or radiotherapy). Exclusion Criteria: have other primary cancer aside from breast cancer. those with residual tumor cells/have experienced second primary breast tumor. patients who are recommended by doctor to switch to aromatase inhibitors (AI)
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: This is a prospective cohort study involving the breast cancer patients who participated in our previous study. Patients who are recommended to adjust their tamoxifen dosage to 40 mg and remain on tamoxifen 20 mg will be all followed up for 3 years to evaluate the clinical outcomes and medication side effects
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose adjustment of tamoxifen<br>Following the CPIC guidelines, those identified as Poor Metabolizers (PMs) and Intermediate Metabolizers (IMs) from our previous study are recommended to adjust their tamoxifen dosage to 40 mg per day. | Drug: Tamoxifen<br>* Suggesting an increase in the dose of tamoxifen to those who have suboptimum level of endoxifen due to their genetic variations<br>|
| No Intervention: Standard dose of tamoxifen<br>Those identified as Normal Metabolizers (NMs) from our previous study remain on tamoxifen 20 mg per day. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival rate | The percentage of study participants who are still alive by the end of this study after being diagnosed with breast cancer | 3 year | 
| Progression Survival rate | The percentage of study participants who live with the disease but the disease does not get worse by the end of this study | 3 year |