<jats:sec><jats:title>Background</jats:title><jats:p>Hormone receptor‐positive breast cancer is the most common subtype; better tools to identify which patients in this group would derive clear benefit from chemotherapy are needed.</jats:p></jats:sec><jats:sec><jats:title>Purpose</jats:title><jats:p>To evaluate the prognostic potential of diffusion‐weighted MRI (DWI) by investigating associations with pathologic biomarkers and a genomic assay for 10‐year recurrence risk.</jats:p></jats:sec><jats:sec><jats:title>Study Type</jats:title><jats:p>Retrospective.</jats:p></jats:sec><jats:sec><jats:title>Subjects</jats:title><jats:p>In all, 107 consecutive patients (from 2/2010 to 1/2013) with estrogen receptor (ER)‐positive/HER2neu‐negative invasive breast cancer who had the 21‐gene recurrence score (RS) test (Oncotype DX, Genomic Health).</jats:p></jats:sec><jats:sec><jats:title>Field Strength/Sequence</jats:title><jats:p>Each subject underwent presurgical 3T breast MRI, which included DWI (b = 0, 800 s/mm<jats:sup>2</jats:sup>).</jats:p></jats:sec><jats:sec><jats:title>Assessment</jats:title><jats:p>Apparent diffusion coefficient (ADC) and contrast‐to‐noise ratio (CNR) were measured for each lesion by a fifth year radiology resident. Pathological markers (Nottingham histologic grade, Ki‐67, RS) were determined from pathology reports. Medical records were reviewed to assess recurrence‐free survival.</jats:p></jats:sec><jats:sec><jats:title>Statistical Tests</jats:title><jats:p>RS was stratified into low (<18), moderate (18–30), and high (>30)‐risk groups. Associations of DWI characteristics with pathologic biomarkers were evaluated by binary or ordinal logistic regression, as appropriate, with adjustment for multiple comparisons. Post‐hoc comparisons between specific groups were also performed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>ADCmean (odds ratio [OR] = 0.61 per 1 standard deviation [SD] increase, adj. <jats:italic>P</jats:italic> = 0.044) and CNR (OR = 1.76 per 1‐SD increase, adj. <jats:italic>P</jats:italic> = 0.026) were significantly associated with increasing tumor grade. DWI CNR was also significantly associated with a high (Ki‐67 ≥14%) proliferation rate (OR = 2.55 per 1‐SD increase, adj. <jats:italic>P</jats:italic> = 0.026). While there were no statistically significant linear associations in ADC (adj. <jats:italic>P</jats:italic> = 0.80–0.85) and CNR (adj. <jats:italic>P</jats:italic> = 0.56) across all three RS groups by ordinal logistic regression, post‐hoc analyses suggested that high RS lesions exhibited lower ADCmean (<jats:italic>P</jats:italic> = 0.037) and ADCmax (<jats:italic>P</jats:italic> = 0.004) values and higher CNR (<jats:italic>P</jats:italic> = 0.008) compared to lesions with a low or moderate RS.</jats:p></jats:sec><jats:sec><jats:title>Data Conclusion</jats:title><jats:p>DWI characteristics correlated with tumor grade, proliferation index, and RS, and may potentially help to identify those with highest recurrence risk and most potential benefit from chemotherapy.</jats:p><jats:p><jats:bold>Level of Evidence</jats:bold>: 3</jats:p><jats:p><jats:bold>Technical Efficacy</jats:bold> Stage 3</jats:p><jats:p>J. Magn. Reson. Imaging 2017.</jats:p></jats:sec>