Efficacy of HER2-targeted therapy in early breast cancer 2008–2020 in Sweden in the real-world setting

Abstract Large-scale real-world evidence on outcomes in HER2-positive (HER2 +) early breast cancer (EBC) remains limited. We investigated overall survival (OS) and its prognostic factors in patients with HER2+ EBC. We here analyzed data from 4,638 patients with HER2 + EBC diagnosed between 2008 and 2020, retrieved from the Swedish National Quality Register for Breast Cancer across four regions in southern Sweden. Associations between demographic, clinical, pathological variables, year of diagnosis, and OS were assessed using Cox proportional hazards models. The median age at diagnosis was 57 years (interquartile range 47 – 65). On multivariable analysis, age > 75 years (adjusted hazard ratio [AHR] = 2.61, P < 0.001), advanced tumor stage (T4 vs. T1; AHR = 4.30, P < 0.001), node-positive disease (AHR = 1.94, P < 0.001), and invasive lobular carcinoma (ILC vs. invasive ductal carcinoma; AHR = 1.59, P = 0.024) were independently associated with worse OS. In contrast, premenopausal status (AHR = 0.52, P < 0.001), radiotherapy (AHR = 0.59, P < 0.001) and treatment with modern HER2-targeted therapies (AHR = 0.70, P = 0.032) were associated with improved OS. Stratified analyses demonstrated that ILC and year of diagnosis were prognostic only in estrogen receptor (ER)-negative disease, whereas the survival benefit of modern HER2-targeted therapy was confined to ER-positive disease. In conclusion, OS in HER2 + EBC has improved over time, reflecting advances in HER2-targeted therapies and comprehensive multimodal treatment strategies.