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Bikeev Yu.V., Sencha A.N., Kolyadina I.V., Tsallagova Z.S., Kotlyarov P.M., Kureneva N.V.
Contrast-enhanced ultrasound examination of invasive breast cancer: opportunities for determining the molecular subtype and predicting axillary metastasis
Keywords: contrast-enhanced ultrasound examination, breast cancer, perfusion defects, molecular subtype of the tumor, axillary lymph nodes
Contrast-enhanced ultrasound examination expands the opportunities of multiparametric ultrasound examination due to functional assessment of tumour microcirculation and angioarchitecture. The molecular biological subtypes of breast cancer differ in biology and clinical progression, which is potentially reflected in the dynamics of perfusion during contrast-enhanced ultrasound. The search for ultrasound markers that can predict the phenotype of the tumor and the risk of metastasis to the axillary lymph nodes prior to a tumor biopsy is of practical importance for personalization, routing and treatment. However, there is still insufficient data on reproducible signs of contrasting in different phenotypes and degrees of malignancy. The aim of the study was to evaluate the diagnostic informative value of qualitative and quantitative ultrasound contrast parameters in the differential diagnosis of molecular subtypes of breast cancer and the degree of tumor differentiation, as well as in predicting metastatic lesions of the axillary lymph nodes. Materials and methods. The prospective single-center study included 76 patients with invasive primary operable breast cancer (stage I–IIIa) between May and September 2024. Ultrasound examination was performed in B-mode and color Doppler mapping mode, followed by contrast-enhanced ultrasound examination (intravenous bolus injection of sulfur hexafluoride (SonoVue, 2.4 ml)). Qualitative signs (homogeneity, gain intensity, wash-in/wash-out, contours, perfusion defects, etc.) and quantitative parameters (TTP, PI, AS, DS) were analyzed. Postoperative histological and immunohistochemical data were considered as reference ones; cFischer test, Mann-Whitney U–test, logistic regression and ROC analysis were applied. Results. Luminal subtypes prevailed in the general cohort (90.6%); metastases to axillary lymph nodes were detected in 25% of cases. The most common contrast patterns were heterogeneous gain (79%), hyperintensive accumulation (85.7%), rapid wash-in (78.6%) and accelerated wash-out (73.8%). In terms of quantitative parameters, tumors with a non–luminal phenotype were characterized by a shorter time to peak (TTP: 6.5 s, in luminal subtypes – 9.9 s; p < 0.05); tumors of the non-luminal HER2+ subtype demonstrated the most "dynamic" perfusion curves and a more pronounced wash-out (DS is statistically lower compared to luminal ones; p < 0.05). There was no significant relationship between the parameters of contrast ultrasound examination and the degree of malignancy (G1–2 vs G3) in the presence of trends towards greater heterogeneity in less differentiated tumors. For the prognosis of axillary metastasis, an association of "absence of rapid wash-in" with the presence of metastases in axillary lymph nodes (OR 4.7; 95% CI 1.5–14.8; p = 0.006), as well as an increase in TTP in patients with metastases (11.85 s / 9.89 s; p < 0.05) was revealed; the diagnostic effectiveness of TTP was moderate (AUC ≈0.66; sensitivity 68%, specificity 59%). Conclusions. The technique of ultrasound examination using an echocontrast preparation makes it possible to identify differences in perfusion characteristics of breast cancer depending on its molecular subtype: non-luminal HER2+ tumors have a more aggressive wash-in/wash-out profile, and triple negative cancer more often demonstrates a peripheral type of contrasting with delayed centralization. Luminal subtypes occupy an intermediate position and are worse differentiated by the isolated parameters of ultrasound contrast, which justifies the need for an integrated approach. The wash-in and TTP parameters can serve as additional markers for predicting axillary lymph node damage, but their predictive accuracy is limited and requires confirmation in more subtype-balanced samples.
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About authors
- Bikeev Yuriy V.
- Candidate of Medical Sciences, Ultrasound Diagnostic Physician, Department of Ultrasound and Functional Diagnostics, Visual Diagnostics Division; Oncologist, Researcher, Department of Breast Pathology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Russia, Moscow (yu_bikeev@oparina4.ru; ORCID: https://orcid.org/0009-0000-3757-5025)
- Sencha Alexander N.
- Doctor of Medical Sciences, Head of the Visual Diagnostics Division, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov; Professor, Department of Ultrasound Diagnostics, N.I. Pirogov Russian National Research Medical University, Russia, Moscow (a_sencha@oparina4.ru; ORCID: https://orcid.org/0009-0005-1597-1920)
- Kolyadina Irina V.
- Doctor of Medical Sciences, Professor, Leading Researcher, Department of Breast Pathology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov; Professor, Department of Oncology and Palliative Medicine named after Academician A.I. Savitsky, Russian Medical Academy of Postgraduate Education, Russia, Moscow (i_kolyadina@oparina4.ru; ORCID: https://orcid.org/0000-0002-1124-6802)
- Tsallagova Zemfira S.
- Doctor of Medical Sciences, Professor, Academic Secretary, Russian Scientific Center for Roentgenoradiology, Russia, Moscow (zscallagova@rncrr.ru; ORCID: https://orcid.org/0000-0003-3199-0804)
- Kotlyarov Petr M.
- Doctor of Medical Sciences, Professor, Chief Researcher, Laboratory of Roentgenoradiology, Research Department of Complex Diagnostics of Diseases and Radiotherapy, Russian Scientific Center for Roentgenoradiology, Russia, Moscow (marnad@list.ru; ORCID: https://orcid.org/0000-0003-1940-9175)
- Kureneva Natalya V.
- Ultrasound Diagnostic Physician, Department of Ultrasound and Functional Diagnostics, Visual Diagnostics Division, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Russia, Moscow (n_kureneva@oparina4.ru; )
Article link
Bikeev Yu.V., Sencha A.N., Kolyadina I.V., Tsallagova Z.S., Kotlyarov P.M., Kureneva N.V. Contrast-enhanced ultrasound examination of invasive breast cancer: opportunities for determining the molecular subtype and predicting axillary metastasis [Electronic resource] // Acta medica Eurasica. – 2026. – №1. P. 1-13. – URL: https://acta-medica-eurasica.ru/en/single/2026/1/1/. DOI: 10.47026/2413-4864-2026-1-1-13.