This retrospective study examined magnetic resonance imaging (MRI)–derived tumor sphericity (SPH) as a quantitative measure of breast tumor morphology, and investigated the association between SPH and reader-assessed morphological pattern (MP). In addition, association of SPH with pathologic complete response was evaluated in patients enrolled in an adaptively randomized clinical trial designed to rapidly identify new agents for breast cancer. All patients underwent MRI examinations at multiple time points during the treatment. SPH values from pretreatment (T0) and early-treatment (T1) were investigated in this study. MP on T0 dynamic contrast-enhanced MRI was ranked from 1 to 5 in 220 patients. Mean SPH values decreased with the increased order of MP. SPH was higher in patients with pathologic complete response than in patients without (difference at T0: 0.04, 95% confidence interval [CI]: 0.02–0.05, P < .001; difference at T1: 0.03, 95% CI: 0.02–0.04, P < .001). The area under the receiver operating characteristic curve was estimated as 0.61 (95% CI, 0.57–0.65) at T0 and 0.58 (95% CI, 0.55–0.62) at T1. When the analysis was performed by cancer subtype defined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, highest area under the receiver operating characteristic curve were observed in HR−/HER2+: 0.67 (95% CI, 0.54–0.80) at T0, and 0.63 (95% CI, 0.51–0.76) at T1. Tumor SPH showed promise to quantify MRI MPs and as a biomarker for predicting treatment outcome at pre- or early-treatment time points.