Survival Outcomes and Recurrence Patterns of Early-Stage HER2-Positive Breast Cancer Patients on Adjuvant T-DM1 Treatment: Turkish Oncology Group (TOG) Study.

[PURPOSE] This study aimed to investigate the survival outcomes of adjuvant trastuzumab emtansine (T-DM1) in patients with early-stage HER2-positive breast cancer and the recurrence patterns in those who experienced recurrence.

[METHODS] This multicenter, retrospective study included 121 patients with early-stage HER2-positive breast cancer who underwent surgery following neoadjuvant chemotherapy and anti-HER2 therapy and received adjuvant T-DM1 for residual disease. Recurrence within the first 12 months of adjuvant T-DM1 was defined as ``early recurrence,'' while recurrence after 12 months (> 12 months) was defined as ``late recurrence.'

[' RESULTS] With a median follow-up of 36 months, recurrence occurred in 23 patients (median time: 11 months). Twenty-two had distant metastases-most commonly lung (n = 14) and CNS (n = 6)-and one had local recurrence. The recurrent subgroup had higher Ki67, tumor grade, and HR-negativity rate (P = .015, P = .034, and P = .014, respectively). Among recurrences, 12 were early (≤ 12 months) and 11 were late recurrence (> 12 months). Patients with early recurrence were significantly younger (P = .007) and had a numerically higher median Ki67 (40% vs. 30%, P = .062). DFS rates at 12, 24, and 36 months were 93.3%, 75.2%, and 62.8%, respectively; OS rates were 100%, 98.3%, and 93.1%.

[CONCLUSIONS] Younger patients with HR-negative, high-grade, high Ki67 tumors had significantly higher rates of recurrence. Defining patient subpopulations through biomarker identification is crucial for tailoring escalation and de-escalation strategies, thereby enabling more effective treatments and improved long-term survival. The mechanisms of T-DM1 resistance require investigation through larger trials and molecular profiling.