Ultrasound Imaging Morphology is Associated with Biological Behavior in Invasive Ductal Carcinoma of the Breast

Abstract
Objectives: Ultrasound (US) is commonly used for diagnostic evaluation of breast lesions. The objective of this study was to investigate the association between US imaging morphology from routine radiologists’ interpretation and biological behavior such as receptor status and tumor grade determined from histopathology in invasive ductal carcinoma (IDC). Material and Methods: This retrospective study included 453 patients with pathology-verified diagnosis of IDC who had undergone US imaging and had surgery over a 5-year period. US and surgical pathology reports were reviewed and compiled. Correlation analyses and age-adjusted multivariable models were used to determine the association between US imaging morphology and receptor status, tumor grade, and germ line mutation of the breast cancer genes (BRCA1 and BRCA2). The odds ratio (OR), area under receiver operating characteristic curve (AUC), and 95% confidence intervals (CI) were obtained. Results: The likelihood for high-grade cancer increased with size (OR: 1.066; CI: 1.042–1.091) and hypo-echogenicity (OR: 2.044; CI: 1.337–3.126), and decreased with angular or spiculated margins (OR: 0.605; CI: 0.393–0.931) and posterior acoustic shadowing (OR: 0.352; CI: 0.238–0.523). These features achieved an AUC of 0.799 (CI: 0.752–0.845) for predicting high-grade tumors. The likelihood for Estrogen Receptor-positive tumors increased with posterior acoustic shadowing (OR: 3.818; CI: 2.206–6.607), angulated or spiculated margins (OR: 2.596; CI: 1.159–5.815) and decreased with US measured tumor size (OR: 0.959; CI: 0.933–0.986) and hypoechoic features (OR: 0.399; CI: 0.198– 0.801), and achieved an AUC of 0.787 (CI: 0.733–0.841). The likelihood for Progesterone Receptor-positive tumors increased with posterior acoustic shadowing (OR: 2.732; CI: 1.744–4.28) and angulated or spiculated margins (OR: 2.618; CI: 1.412–4.852), and decreased with US measured tumor size (OR: 0.961; CI: 0.937–0.985) and hypoechoic features (OR: 0.571; CI: 0.335–0.975), and achieved an AUC of 0.739 (CI: 0.689–0.790). The likelihood for Human epidermal growth factor receptor 2-positive tumors increased with heterogeneous echo texture (OR: 2.141; CI: 1.17– 3.919) and decreased with angulated or spiculated margins (OR: 0.408; CI: 0.177–0.944), and was marginally associated with hypoechoic features (OR: 2.101; CI: 0.98–4.505) and circumscribed margins (OR: 4.225; CI: 0.919–19.4). The model with the aforementioned four US morphological features and achieved an AUC of 0.686 (CI: 0.614–0.758). The likelihood for triple-negative breast cancers increased with hypo-echogenicity (OR: 2.671; CI: 1.249–5.712) and decreased with posterior acoustic shadowing (OR: 0.287; CI: 0.161–0.513), and achieved an AUC of 0.739 (CI: 0.671– 0.806). No statistical association was observed between US imaging morphology and BRCA mutation. Conclusion: In this study of over 450 IDCs, significant statistical associations between tumor grade and receptor status with US imaging morphology were observed and could serve as a surrogate imaging marker for the biological behavior of the tumor.