Abstract P2-03-24: Cost-Effectiveness of CYP2D6 Genotyping in the Management of Tamoxifen Therapy for Breast Cancer Patients: A Focus on Adverse Events

Background: Tamoxifen, an antiestrogen prodrug, is widely used in treating hormone receptor-positive breast cancer. Its efficacy largely depends on its conversion to the active metabolite endoxifen by the CYP2D6 enzyme, which exhibits varying levels of activity based on genetic polymorphisms. Current clinical practice guidelines recommend an initial gynecological examination with transvaginal ultrasound before starting tamoxifen. If no abnormalities are detected, the patient begins tamoxifen without additional gynecological follow-up unless symptomatic (e.g., spotting or vaginal bleeding). This study explores the cost-effectiveness of CYP2D6 genotyping to predict patients at higher risk of toxicity. Methods: This analysis utilized data from our dose escalation trial (EudraCT: 2007-002942-40), where poor metabolizers (PM) received increased doses of tamoxifen. All women were treated with 20 mg/day of tamoxifen for 5 years, except PM, who received 20 mg/day for 4 months, 40 mg/day for the next 4 months, and 60 mg/day for another 4 months before returning to 20 mg/day for the remainder of the 5 years. The costs for managing adverse events, updated in May 2024, were obtained from the Andalusian Health Service. These costs provide a detailed financial perspective based on public data, including costs for consultations, diagnostic procedures, follow-up treatments, and hospitalization, reflecting Grade 2 complexity. Additionally, we calculated the cost of CYP2D6 genotyping, covering expenses for DNA extraction, analysis using KASP assays, and proration of personnel and equipment costs. We analyzed the incidence of specific side effects: osteoarticular pain, hot flashes, asthenia, and gynecological alterations. Results: Only gynecological alterations showed significant differences between CYP2D6 phenotypes. The incidence of gynecological adverse events was significantly higher in slow metabolizer (SM) patients (44.8%) compared to rapid metabolizer (RM) patients (15.2%, p=0.001). Adverse events quantified as average cost per patient include endometrial hyperplasia (€8544,81), endometrial polyps (€1834,56), adenocarcinoma (€9467,96), and endometrial thickening (€1132,27). Although costs related to medications, secondary events, extended hospital stays, or patient evolution were not included, our study recorded an average of 0.75 emergency visits per patient (range: 0-4), each costing €208.47 without hospital admission or observation. The cost of CYP2D6 genotyping is minimal (€10.98) compared to managing gynecological adverse events. Conclusion: Considering the significant impact of CYP2D6 polymorphisms on the occurrence of gynecological adverse events and the substantial cost of managing these events, our results advocate for the implementation of CYP2D6 genotyping. Given its demonstrated cost-effectiveness, we propose CYP2D6 genotyping for all patients scheduled to receive tamoxifen. For those with a predicted SM phenotype, we recommend protocolized gynecological follow-up at least once a year, along with thorough clinical monitoring. Any emerging symptoms should prompt immediate referral to gynecology for evaluation and examination. This approach not only enhances the quality of care but also aligns with healthcare efficiency objectives.

Citation Format: Isabel Blancas, Xando Díaz-Villamarín, Carlos José Rodríguez-González, Rocío Morón-Romero, Fernando Rodríguez-Serrano. Cost-Effectiveness of CYP2D6 Genotyping in the Management of Tamoxifen Therapy for Breast Cancer Patients: A Focus on Adverse Events [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-03-24.