In recent years, neoadjuvant treatment trials have shown that breast cancer subtypes identified on the basis of genomic and/or molecular signatures exhibit different response rates and recurrence outcomes, with the implication that subtype-specific treatment approaches are needed. Estrogen receptor-positive (ER+) breast cancers present a unique set of challenges for determining optimal neoadjuvant treatment approaches. There is increased recognition that not all ER+ breast cancers benefit from chemotherapy, and that there may be a subset of ER+ breast cancers that can be treated effectively using endocrine therapies alone. With this uncertainty, there is a need to improve the assessment and to optimize the treatment of ER+ breast cancers. While pathology-based markers offer a snapshot of tumor response to neoadjuvant therapy, non-invasive imaging of the ER disease in response to treatment would provide broader insights into tumor heterogeneity, ER biology, and the timing of surrogate endpoint measurements. In this review, we provide an overview of the current landscape of breast imaging in neoadjuvant studies and highlight the technological advances in each imaging modality. We then further examine some potential imaging markers for neoadjuvant treatment response in ER+ breast cancers.

Metabolic imaging of the primary breast tumor with ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG) PET may assist in predicting treatment response in the neoadjuvant chemotherapy (NAC) setting. Dedicated breast PET (dbPET) is a high-resolution imaging modality with demonstrated ability in highlighting intratumoral heterogeneity and identifying small lesions in the breast volume. In this study, we characterized similarities and differences in the uptake of [¹⁸F]FDG in dbPET compared to whole-body PET (wbPET) in a cohort of ten patients with biopsy-confirmed, locally advanced breast cancer at the pre-treatment timepoint. Patients received bilateral dbPET and wbPET following administration of 186 MBq and 307 MBq [¹⁸F]FDG on separate days, respectively. [¹⁸F]FDG uptake measurements and 20 radiomic features based on morphology, tumor intensity, and texture were calculated and compared. There was a fivefold increase in SUL_peak for dbPET (median difference (95% CI): 4.0 mL^-1 (1.8-6.4 mL^-1), p = 0.006). Additionally, spatial heterogeneity features showed statistically significant differences between dbPET and wbPET. The higher [¹⁸F]FDG uptake in dbPET highlighted the dynamic range of this breast-specific imaging modality. Combining with the higher spatial resolution, dbPET may be able to detect treatment response in the primary tumor during NAC, and future studies with larger cohorts are warranted.