Risk factors and metastatic sites in HER2-positive breast cancer with pathological complete response

A pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is associated with favorable outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer; however, brain metastases still occur. Using the National Clinical Database-Breast Cancer Registry (JAPAN 2008-2020), we identified 21,494 patients who received NAC followed by surgery. After excluding cases without pCR status or prognostic data, 8421 patients were analyzed (2430 pCR; 5991 non-pCR). Disease-free survival (DFS), brain metastasis-free survival, and recurrence patterns were compared, and risk factors for distant recurrence were evaluated. Patients achieving pCR had significantly better 5-year DFS than non-pCR patients. Among pCR cases, hormone receptor status and clinical stage independently predicted recurrence. At 5 years, brain metastases occurred in 2.6% of pCR patients and 4.5% of non-pCR patients. These findings indicate that pCR does not eliminate the risk of brain metastases, highlighting the need for continued vigilance.