Background: The real-world risk of disease recurrence in patients with HER2+ early breast cancer who achieved pCR after receipt of nPT-based regimens and aT is unclear. Methods: Women with HER2+ breast cancer who achieved pCR after nPT-based regimens and received aT were identified in the US Oncology Network (USON). Patients initiated nPT between 2013 –2015 and were followed until recurrence of invasive disease or censoring. Data was sourced from structured fields and review of USON patient charts. Recurrence of invasive disease was defined as any of: recurrence of ipsilateral locoregional invasive breast cancer, contralateral breast cancer, distant disease recurrence, or death. Descriptive analyses were used to assess baseline demographic and clinical characteristics and the Kaplan-Meier method was used to assess invasive disease-free survival (iDFS), with stratification by nodal status. Results: A total of 238 pCR patients’ charts were reviewed. Median patient age was 52 (range: 23-88) years and a majority were White (77%). Most patients had stage IIA (39%) or IIB (24%) disease at diagnosis, ECOG score < 1 (85%), and tumor size > 2 cm (68%). At diagnosis, the majority of patients (57%) were node positive (N+) and negative for estrogen or progesterone receptor expression (51%). Median durations of therapy for nPT and aT were 4 (range: 1-8) and 7 (range: 0.03-53) months, respectively. The median duration of follow up was 47 (range: 1-70) months. Four-year iDFS probabilities are shown in the Table. Conclusions: Consistent with previously reported clinical trial data and several pooled analyses, results from this real-world study indicate that despite achieving pCR after nPT-based regimens, patients with HER2+ BC remain at risk for disease recurrence; in addition, node+ status appears to increase that risk. Therefore, patients should receive standard pertuzumab, trastuzumab adjuvant therapy to optimize treatment outcomes.