Table 2.

Summary of described recent studies on CYP2D6 genotyping, and additional factors on plasma concentrations endoxifen.

Reference	End-Point	N. PTS.	Material and Methods	Results
Thorén et al., 2020 [70] Nardin et al., 2020 [71]	Endoxifen plasma concentrations in PM, IM, NM, and UM patients	118, 192	CYP2D6 genotyping; LC-MS/MS	CYP2D6 metabolizer status is a strong determinant of plasma endoxifen concentrations. Increasing CYP2D6 allele activity correlates with increasing endoxifen levels.
Khalaj et al., 2019 [72] Tamura et al., [73]	Endoxifen plasma concentrations in PM, IM, NM, and UM patients	134, 186	CYP2D6 genotyping; LC-MS/MS	Dose escalation in CYP2D6-compromised patients (PMs and IMs combined) resulted in an increase in endoxifen levels, similar as NMs (using standard dosage of 20 mg/day). No difference in the occurrence of the most common side effect (hot flushes) or severe side effects was found.
Nardin et al., 2020 [71]	Endoxifen plasma concentrations in PM, IM, NM and UM patients; Patient adherence behavior	192	CYP2D6 genotyping; LC-MS/MS; Morisky, Green, and Levine medication adherence scale	Adherence explained 47% of tamoxifen variability (p < 0.001). Combination of patients adherence and CYP2D6 genotype explained 40% of endoxifen variability at 12 months (p < 0.001). So, endoxifen levels are influenced both by patients’ tamoxifen treatment adherence and CYP2D6 genotype.
He et al., 2020 [78]	Tamoxifen discontinuation	1309	CYP2D6 genotyping; Self-reported questionnaires	UMs show a significantly higher discontinuation rate at 6 months after start of tamoxifen treatment (18.8%) compared to NMs (6.7). No significant difference in tamoxifen discontinuation was found for PMs (7.1%) or IMs (7.6%). After 6 months, no significant difference in discontinuation rates was found.
Monte et al., 2018 [84]	Dextro-methorphan (DM)/dextror-phan (DX) ratio in PM, IM, NM, and UM patients	39	CYP2D6 genotyping; Plasma DM and DX assay using LC-MS	Patients with co-ingestion of dextromethorphan (as CYP2D6 enzyme probe drug) and another CYP2D6-dependent drug were 9.5 times more likely to have genotype-phenotype discordance based upon the 3 h DX/DM ratio.