Hayah Naveed

Background: Breast cancer mortality is driven primarily by metastatic spread rather than by the primary tumor alone, making earlier identification of biologically aggressive disease a major clinical priority.^1,2 Conventional full-field mammography remains the standard screening tool, but it is limited in dense breasts and provides mostly structural rather than functional information about tumor biology.¹ Tumor angiogenesis and abnormal microvasculature are central to invasion, lymphovascular spread, and nodal metastasis, suggesting that vascular imaging may offer a noninvasive way to identify tumors with metastatic potential before clinical signs become apparent.¹ Current imaging approaches, including contrast-enhanced spectral mammography (CESM), contrast-enhanced mammography (CEM), dynamic contrast-enhanced MRI (DCE-MRI), and quantitative high-definition microvasculature imaging (qHDMI), each capture different aspects of this vascular phenotype and may help reveal biologic aggressiveness that is not visible on conventional imaging.^3-7 This review addresses the gap between lesion detection and biologic risk stratification by evaluating whether vascular imaging features can better predict metastatic behavior than conventional morphology alone.

Objective: To determine whether imaging markers of tumor vascularity can serve as surrogate biomarkers of aggressive breast cancer biology and help predict metastatic potential.

Methods: Literature was identified using PubMed-based searches from 2015 to 2026. Search terms included combinations of “breast cancer”, “angiogenesis”, “metastasis”, “vascular imaging”, “contrast-enhanced mammography”, “abbreviated MRI”, “ultrasound”.

Results: CESM/CEM studies showed that malignant lesions are associated with irregular shape, ill-defined or spiculated margins, heterogeneous or intense internal enhancement, and ductal, segmental, or clumped non-mass enhancement patterns.³ These descriptors improved diagnostic performance compared with standard mammography and reflect disorganized neovasculature. In the BRAID trial, contrast-based supplemental imaging detected roughly three times as many invasive cancers as automated whole-breast ultrasound in women with dense breasts, but at the cost of increased recall and biopsy rates.⁴ DCE-MRI provided a mechanistic link between imaging and histology, showing higher microvessel density correlated with increased peak signal enhancement ratio and washout fraction, supporting these metrics as biomarkers of angiogenic activity.⁵ qHDMI further extended this concept by objectively quantifying vessel density, branching complexity, tortuosity, and related microvascular features without contrast, and invasive ductal carcinoma showed more complex vascular networks than radial scar.⁷ In invasive micropapillary carcinoma, a highly aggressive subtype, pathologic enhancement on CEM aligned with frequent lymphovascular invasion and nodal disease, reinforcing the association between vascular imaging signatures and metastatic behavior.⁶

Conclusion: Across modalities, vascular imaging consistently identifies imaging phenotypes associated with aggressive breast cancer biology and metastatic risk.^3-7 These findings support the development of a composite vascular-imaging framework to help prioritize biopsy, refine axillary staging, and guide treatment escalation. Future prospective studies should determine which combination of vascular markers best predicts lymphovascular invasion, nodal spread, and distant recurrence while balancing improved detection against higher recall and biopsy burden.⁴

Works Cited

1. Ghalehbandi S, Yuzugulen J, Pranjol MZI, Pourgholami MH. The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF. Eur J Pharmacol. 2023;949:175586.
2. Mahjabeen F, Habbani SF, Mohammed SI. Molecular Mechanisms of Lymphatic Metastasis in Breast Cancer: An Updated Review. Cancers (Basel). 2025;17(13):2134.
3. Mohamed Kamal R, Hussien Helal M, Wessam R, et al. Contrast-enhanced spectral mammography: Impact of the qualitative morphology descriptors on the diagnosis of breast lesions. Eur J Radiol. 2015;84(6):1049-1055.
4. Gilbert FJ, Payne NR, Allajbeu I, et al. Comparison of supplemental breast cancer imaging techniques-interim results from the BRAID randomised controlled trial. Lancet. 2025;405(10493):1935-1944.
5. Xiao J, Rahbar H, Hippe DS, et al. Dynamic contrast-enhanced breast MRI features correlate with invasive breast cancer angiogenesis. NPJ Breast Cancer. 2021;7(1):42.
6. Fakhry S, Nada YMAI, Mohamed MM, et al. Radiological characteristics of invasive micropapillary carcinoma of the breast. Clin Radiol. 2024;79(1):e34-e40.
7. Sabeti S, Adl Parvar T, Metanat P, et al. Quantitative angiogenesis-based ultrasound biomarkers for differentiating radiologically challenging breast lesions: radial scar vs invasive ductal carcinoma. Breast. 2025;84:104614.