Abstract Background: Patients with early or locally advanced breast cancer achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy have a lower risk for recurrence or death compared to patients with residual invasive cancer. In the future, breast surgery might be avoided in patients in whom the presence of residual tumor after neoadjuvant therapy can be ruled out with very high confidence. Magnetic resonance imaging (MRI) has been shown to be the most accurate radiologic tool in breast cancer diagnostics and follow-up care. Therefore, we investigated the diagnostic accuracy of contrast-enhanced MRI to predict a pathological complete remission after neoadjuvant chemotherapy. Methods: This retrospective study included all non-metastatic breast cancer patients treated with neoadjuvant chemotherapy followed by a contrast-enhanced MRI and breast cancer surgery at our institution between 09/2006 and 05/2016. Three specialized breast radiologists, blinded to the clinical and pathological data, reevaluated all preoperative MRI scans and recorded the presence or absence of contrast enhancement as indicator for residual cancer. pCR was defined as no invasive tumor in breast and axilla (ypT0/is N0), however 3 alternative definitions were investigated as well (ypT0 N0, ypT0/is and ypT). Cross tables were used to calculate sensitivity, specificity, pCR-predictive value (PPV), non-pCR-predictive value (NPV) and accuracy. P-values reflecting PPV and NPV differences between various patient subgroups were calculated with Fisher's exact test. The Kaplan-Meier method was used for estimates of distant-recurrence-free survival (DRFS) and overall survival (OS). Results: In total, 246 patients fulfilled the inclusion criteria and were evaluated. Overall pCR and radiologic complete remission (rCR) rate were 29% and 45%, respectively. Only 48% of rCR corresponded to a pCR (PPV). Conversely, in 87% of cases, residual tumor in the MRI was pathologically confirmed (NPV). The sensitivity to detect a pCR was 75%, while specificity and accuracy were 67% and 69%, respectively. The diagnostic performance of MRI to predict treatment response varied between different histologic and molecular tumor subtypes, however there were little differences between the 4 pCR definitions. The PPV was significantly lower in the hormone-receptor(HR)-positive subgroup compared with the HR-negative subgroup (33% vs. 61%; P = 0.004), especially in luminal-A-like (7%) and lobular carcinomas (0%), respectively. Despite the low concordance (Kohens kappa -0.1), the prognostic value for distant recurrence-free survival was similar between rCR (HR 0.29) and pCR (HR 0.27), respectively. The median pathologic tumor size of residual disease in false-positive cases (rCR but no pCR) was 0.7 cm (SD 0.98 cm). Conclusion: Contrast-enhanced MRI does not accurately predict pCR after neoadjuvant chemotherapy in early or locally advanced breast cancer, especially in HR-positive tumors. However, in case of false rCR the dimension of residual disease is generally small. Since residual tumor tissue can be detected with high precision, preoperative breast MRI is still of value for operation planning. Citation Format: Gampenrieder SP, Peer A, Weismann C, Meissnitzer M, Rinnerthaler G, Webhofer J, Westphal T, Popovscaia M, Meissnitzer T, Reitsamer R, Hauser-Kronberger C, Egger H, Hergan K, Mlineritsch B, Greil R. Contrast-enhanced MRI does not accurately predict pathologic complete response (pCR) after neoadjuvant chemotherapy in early or locally advanced breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-02-02.