Accuracy and Reproducibility of Contrast-Enhanced Mammography in the Assessment of Response to Neoadjuvant Chemotherapy in Breast Cancer Patients with Calcifications in the Tumor Bed

Abstract

This study aimed to evaluate contrast-enhanced mammography (CEM) accuracy and reproducibility in the detection and measurement of residual tumor after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients with calcifications, using surgical specimen pathology as the reference. Pre- and post-NAC CEM images of 36 consecutive BC patients receiving NAC in 2012-2020, with calcifications in the tumor bed at diagnosis, were retrospectively reviewed by two radiologists; described were absence/presence and size of residual disease based on contrast enhancement (CE) only and CE plus calcifications. Twenty-eight patients (77.8%) had invasive and 5 (13.9%) in situ-only residual disease at surgical specimen pathology. Considering CE plus calcifications instead of CE only, CEM sensitivity for invasive residual tumor increased from 85.7% (95% CI = 67.3-96%) to 96.4% (95% CI = 81.7-99.9%) and specificity decreased from 5/8 (62.5%; 95% CI = 24.5-91.5%) to 1/8 (14.3%; 95% CI = 0.4-57.9%). For in situ-only residual disease, false negatives decreased from 3 to 0 and false positives increased from 1 to 2. CEM pathology concordance in residual disease measurement increased (R squared from 0.38 to 0.45); inter-reader concordance decreased (R squared from 0.79 to 0.66). Considering CE plus calcifications to evaluate NAC response in BC patients increases sensitivity in detection and accuracy in measurement of residual disease but increases false positives.

Keywords: breast cancer; calcifications; contrast-enhanced mammography; neoadjuvant chemotherapy; treatment monitoring.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

False positive for the combined evaluation and true negative for the CE evaluation: 67-yo woman with IDC G2 HER2+ with opacity and inner pleomorphic calcifications in the outer quadrant of the right breast (A,C: canio-caudal (CC) low-energy image). The in situ component was seen only on the surgical specimen. The opacity showed a strong mass enhancement before NAC (C: CC recombined image). After NAC (B: CC low-energy image; D: CC recombined image), the calcifications decreased slightly in size; remaining pleomorphic, they were considered pathological (B, arrow); no residual enhancement was visible surrounding the marker placed in the tumor bed, in the site of the previous opacity. The analysis of the surgical specimen revealed a complete response ypT0.

Figure 2

True positive for the combined evaluation and false negative on the CE-only evaluation: 55-yo woman with IDC G2 HER2+ with opacity and nearby, two clusters of pleomorphic calcifications in right breast (A,C: CC low-energy image; arrows). The in situ component was seen only on the surgical specimen. The opacity showed a strong mass enhancement before NAC (C: CC recombined image), while the clusters of calcifications showed no or only faint enhancement. After NAC (B: CC low-energy image; D: CC recombined image), the calcifications in both clusters decreased slightly (B, arrows); no residual enhancement was visible surrounding the marker placed in the tumor bed of the opacity. The analysis of the surgical specimen revealed 12 mm of residual IDC and multiple foci of DCIS (ypT1c).

Figure 3

Linear regressions with respective R squared coefficients of CEM size measurement with pathology size measurement, respectively, for Reader 1 considering CE only (A), for Reader 1 considering CE + calcifications (B), for Reader 2 considering CE only (C), and for Reader 2 considering CE + calcifications (n = 31) (D). Squares represent cases with patchy shrinkage. Red dots and squares represent cases with in situ component in the residual tumor bed.

Figure 4

Linear regressions depicting concordance between the two CEM readers when considering CE only (A) and CE plus calcifications (B) (n = 36).

Figure 5

Inter-reader discordance in the evaluation of calcifications: 54-yo woman with IDC G3 HER2+ with opacity and nearby calcifications in left breast (A,B: medio-lateral-oblique (MLO) low-energy image). The in situ component was seen both on the initial biopsy and on the surgical specimen. For Reader 1, the calcifications after NAC remained pleomorphic and were considered as the measurement of the residual disease because more extensive (114 mm; C) than the concomitant faint residual rim enhancement (10 mm; D: MLO recombined image). For Reader 2, the same patient presented with a cluster of 15 mm of indeterminate calcifications after NAC (C), and thus considered CE only for the measurement of residual disease (10 mm; D). The analysis of surgical specimens reveled 15 mm of IDC and DCIS, with a better concordance for Reader 2 vs. Reader 1.