Early, delayed, or combined contrast-enhanced mammography for detecting residual disease after neoadjuvant chemotherapy in breast cancer

Objectives: To evaluate the diagnostic performance of contrast-enhanced mammography (CEM) for detecting residual disease (RD) and assessing residual tumor size after neoadjuvant chemotherapy (NAC) in breast cancer, comparing early-only, delayed-only, and combined acquisition protocols. Materials and methods: This retrospective single-center diagnostic performance study included consecutive women with biopsy-proven breast cancer who underwent pre- and post-NAC CEM with both early and delayed acquisitions and subsequent surgery (2016-2024). Patients without complete CEM protocols or surgical pathology were excluded. CEM images were independently analyzed for each protocol by two experienced breast radiologists in consensus. Radiological response was categorized per RECIST and dichotomized as complete response versus RD. Pathological tumor staging (ypT) at surgery was the gold standard; pathologic complete response (pCR) was defined as ypT0/ypTis. Diagnostic performance in predicting RD was calculated for each protocol with sensitivity and negative predictive value (NPV) as primary endpoints (χ² test). Bland-Altman analysis compared imaging-measured and pathological tumor sizes. Results: Of 202 women included (mean age, 54.7 ± 12.7), 83 (41.1%) achieved pCR. Sensitivity for detecting RD was higher for delayed (85.7%, 95% CI 78.1-91.5%) and combined protocols (86.6%, 79.1-92.1%) compared to early (68.1%, 58.9-76.3%; p < 0.0001). NPV improved from 58.2% (95% CI 48.3-67.6%) to 71.2% (62.3-79.0%; p = 0.04) with delayed acquisitions. Bland-Altman analysis showed slightly better agreement between early images and pathology (mean difference 5.7 mm) than for delayed acquisitions (11.8 mm). Conclusions: Delayed CEM images significantly improved sensitivity and NPV in predicting RD, supporting the inclusion of delayed acquisitions in the neoadjuvant setting. Key points: Question Can contrast-enhanced mammography protocols be optimized after neoadjuvant chemotherapy to improve the detection of pathological residual disease and residual tumor size assessment? Findings Delayed contrast-enhanced mammography acquisitions significantly improved sensitivity and negative predictive value for residual disease detection, whereas early acquisitions provided slightly better agreement for residual tumor size. Clinical relevance Including delayed images in post-neoadjuvant contrast-enhanced mammography improves detection of residual invasive disease, supporting surgical planning, while early images remain useful for tumor size estimation.