Abstract Background: Neoadjuvant chemotherapy (NAC) is a widely accepted treatment not only for locally advanced breast cancer, but also for earlier-stage operable disease. The main purpose of it is to downstage the tumor and to avoid the extensive operation and increase breast conservation surgery. Recent studies have indicated that patients who achieve a pathologic complete response (pCR) after NAC show better outcomes than patients with residual disease in breast cancer (non-pCR). On the other hand, there are some cases in which cancer recurred despite achieving pCR (pCR-rec). This retrospective study investigates the clinical profiles and outcome associated with the patients whose tumor recurred after achieving pCR after NAC. Patients and Methods: All the clinical and pathologic data were collected from 4 institutions in Japan: Yokohama City University Hospital, Kanagawa Cancer Center, Yokohama Rosai Hospital and Tokyo Medical University Hospital. Total of 1,599 operable breast cancer patients who underwent NAC were enrolled. The median follow-up period was 41 months. Vast majority of the patients were treated with anthracycline followed by taxane-based chemotherapy, with or without trastuzumab as neoadjuvant therapy. We defined pCR as no residual invasive cancer in the breast and axially nodes, and non-pCR was divided into 2 groups as Grade 1 (no to mild response) and Grade 2 (moderate response). Results: Of 1,599 patients enrolled in the study, 363 patients achieved pCR (22.7%). Among the pCR patients, 41 were Luminal type, 93 were Luminal-HER2 type, 109 were HER2 type, and 120 were triple-negative (TN) type (pCR rate was 5.94%, 30.4%, 49.3% and 31.3%, respectively). Cancer recurrence after resection was observed in 18 patients (pCR-rec, 4.9%). Axial nodal metastasis diagnosed before NAC associated to cancer recurrence among the pCR patients (p= 0.0003). pCR patients showed significantly better outcome compared to non-pCR, consistent with the previous reports among all patients. However, pCR-rec showed significantly worse DFS compared to those with Grade 1, Grade 2, or pCR (P<0.005 ; 2-year disease-free rate was 33.3%, 79.1%, 88.9% and 98.6%, respectively), as well as HER2 and TN cohort showed consistent results (P<0.005; 2-year disease-free rate was 14.5%, 63.1%, 83.7%,and 95.0%, and P<0.005; 2-year disease-free rate was 17.9%, 55.7%, 81.7% and [no data]). Conclusions: Although achieving pCR after NAC improved outcome, patients with cancer recurrence after pCR show significantly unfavorable outcome even compared to non-pCR patients. In further study, identifying these patients before treatment could improve their poor survival. Citation Format: Mariko Asaoka, Takashi Ishikawa, Eiichi Sato, Kazutaka Narui, Takashi Chishima, Akimitsu Yamada, Nobuyasu Suganuma, Tsutomu Kawaguchi, Kazuaki Takabe. Clinical profile and outcome associated with breast cancer recurrence after pathologic complete response to neoadjuvant chemotherapy: A multicenter study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 591.