Tamoxifen remains the standard treatment for hormone-sensitive breast cancer. However, significant interindividual variability in treatment response is observed. This variability may be partially explained by differences in the biotransformation of tamoxifen, a prodrug, into its active metabolites. To address this, we conducted a comprehensive literature search across several databases to examine current evidence on single-gene and multi-gene variations throughout the metabolic and transport pathways of tamoxifen and their impact on pharmacokinetics and clinical efficacy. We also explore the influence of drug–drug–gene interactions and review clinical strategies currently employed to manage treatment variability. Overall, growing evidence highlights the influence of pharmacogenetic variability, particularly CYP2D6 polymorphisms, on tamoxifen metabolism. Although its clinical use remains cautious and limited, a combined approach involving pharmacogenetic testing and therapeutic monitoring or phenotyping may help address treatment variability.

Background/Objectives: Synovial sarcoma (SS) is an aggressive soft-tissue tumor characterized by the chromosomal translocation t(X;18) (p11.2;q11.2), most commonly involving the fusion of the SYT gene on chromosome 18 with the SSX1 or SSX2 genes on chromosome X. This study aims to explore the clinicopathological and molecular characteristics of synovial sarcoma in a cohort of Moroccan patients. Methods: We analyzed 48 cases of synovial sarcoma using formalin-fixed, paraffin-embedded (FFPE) tissue samples. Histological grading was performed according to the FNCLCC system. Immunohistochemical staining was employed to detect cytokeratin (CK) and epithelial membrane antigen (EMA). Molecular analysis included fluorescence in situ hybridization (FISH) to identify SS18 gene rearrangements and reverse transcription–polymerase chain reaction (RT-PCR) to detect SYT-SSX fusion transcripts. Results: Among the cohort, 56% of cases showed SS18 gene rearrangements via FISH, while RT-PCR confirmed the presence of SS18-SSX1 and SS18-SSX2 transcripts in 60% and 32% of cases, respectively. The remainder was classified as undifferentiated sarcoma. Notably, no significant associations were observed between SYT-SSX fusion type and clinicopathological features. Conclusions: These findings underscore the importance of integrating molecular techniques for precise diagnosis in synovial sarcoma. The results align with global patterns, emphasizing the necessity for molecular testing to enhance diagnostic accuracy and informing potential therapeutic advancements.