Cost-effectiveness of HER2/neu 655 genotyping in managing trastuzumab-induced cardiotoxicity risk in HER2-positive breast cancer patients.

543 Background: Trastuzumab has significantly improved survival in HER2-positive breast cancer patients. However, around 20% of patients experience cardiotoxicity. Cardiotoxicity has been defined as a ≥10% drop in left ventricular ejection fraction (LVEF) or LVEF <50%, or the appearance of clinical cardiac insufficiency. The HER2/neu 655 A>G polymorphism has been linked to cardiotoxicity risk. This study evaluates the cost-effectiveness of HER2/neu 655 genotyping. Methods: Eighty-eight HER2-positive breast cancer patients treated for early disease with trastuzumab were retrospectively analyzed. All were genotyped for HER2/neu 655 A>G (AA: n=53, AG: n=32, GG: n=3). LVEF was monitored by echocardiography or isotopic ventriculography at baseline and regular intervals. Cardiotoxicity was defined as above. Logistic regression adjusting for hormonal status and anthracycline use estimated the association between genotype and cardiotoxicity. Cost data from the Andalusian Regional Health Service included diagnostic tests, cardiology visits, pharmacologic therapy, and hospitalizations. Results: Among the 53 patients with the AA genotype, 3.7% experienced a decrease in LVEF, while 9.4% developed clinical symptoms. For the AG genotype (32 patients), 9.3% showed an LVEF reduction, and 28.1% presented clinical symptoms. In the GG genotype group (3 patients), 1 patient (33.3%) developed clinical symptoms. AG carriers had a significantly higher risk of cardiotoxicity than AA patients (OR adjusted for hormonal status and anthracycline treatment =4.42; p=0.037). HER2/neu 655 A>G genotyping costs €38. Asymptomatic LVEF reductions usually required 3 cardiology visits including echocardiography (€121.05 each), and one year of pharmacological treatment (carvedilol and/or enalapril therapy; €84.72 total). Cardiac insufficiency costs range from €2,992.61 (grade 1) to €9,363.56 (grade 4). Conclusions: HER2/neu 655 genotyping is cost-effective for identifying patients at higher risk of trastuzumab-induced cardiotoxicity. The low cost of genotyping is outweighed by the potential savings in preventing severe cardiac events. Genotype-driven monitoring and proactive cardiac and targeted cardiovascular risk management in AG carriers could reduce both the incidence and severity of cardiotoxicity.