Comparative effectiveness and safety of adjuvant trastuzumab plus pertuzumab versus trastuzumab emtansine in HER2-positive breast cancer with residual disease after neoadjuvant therapy: a real-world retrospective study.

Purpose: To compare the effectiveness, safety, and tolerability of adjuvant trastuzumab plus pertuzumab (HP) versus trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with residual invasive disease after neoadjuvant therapy, and to perform exploratory analyses of outcomes in clinically favorable subgroups. Materials and methods: Patients with HER2-positive breast cancer and residual invasive disease after NAT, enrolled between 2020 and 2024, were included. Propensity score matching (1:1) was applied to adjust for baseline characteristic differences. Kaplan-Meier survival analysis and Cox proportional hazards models were used to compare survival outcomes (iDFS, RFS, OS) between the two groups. Additionally, the incidence of adverse events and treatment adherence were compared. Results: A total of 272 patients were analyzed, with 134 remaining after propensity score matching. After a median follow-up of 37.7 months, no statistically significant differences in short-term survival outcomes were detected between the two groups. Grade 3 or higher adverse events occurred more frequently in the T-DM1 group, particularly thrombocytopenia. Treatment interruption or regimen modification occurred in 22.7% of patients in the T-DM1 group and 2.2% in the HP group. Conclusion: In HER2-positive breast cancer patients with residual invasive disease after NAT, no statistically significant difference in short-term recurrence or survival outcomes was detected between adjuvant HP and T-DM1, while HP was associated with a more favorable safety and tolerability profile. These findings should be interpreted as complementary real-world evidence in the contemporary dual-blockade era and as hypothesis-generating support for future risk-adapted adjuvant strategies.