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.