Contrast-enhanced ultrasound features as a potential biomarker for the prediction of breast cancer recurrence

Abstract

Purpose To investigate the associations between contrast-enhanced ultrasound imaging features and disease recurrence among patients with locally advanced breast cancer treated with neoadjuvant chemotherapy.

Materials and Methods In the study, pre- and post-neoadjuvant chemotherapy contrast-enhanced ultrasound images of 43 patients with breast cancer were retrospectively analysed. Post-acquisition image processing involved the placement of freehand-drawn regions of interest, followed by the generation of blood flow kinetics representing blood volume and velocity for these regions of interest. Qualitative and quantitative contrast-enhanced ultrasound parameters were compared to predict recurrence, and receiver operating characteristic analysis was used to evaluate predictive ability.

Results Among the 43 patients, 10 (23%) exhibited disease recurrence (median [range]: 27 [4–68] months). Post-neoadjuvant chemotherapy peak enhancement, wash-in area under the curve, wash-out area under the curve, and wash-in and wash-out area under the curve (p=0.003, p=0.004, p=0.026, and p=0.014, respectively) differed between the no-recurrence and recurrence groups. The area under the receiver operating characteristic curve (0.88; 95% confidence interval: 0.75–1.00) for post-neoadjuvant chemotherapy peak enhancement was the highest among the contrast-enhanced ultrasound parameters, with a cut-off of 13.33 arbitrary units.

Conclusion Higher peak enhancement on post-neoadjuvant chemotherapy contrast-enhanced ultrasound images was associated with recurrence in women with locally advanced breast cancer and is a potential biomarker of tumor recurrence.

Zusammenfassung

Ziel Untersuchung, ob ein Zusammenhang zwischen Parametern im kontrastverstärkten Ultraschall und einem Krankheitsrezidiv bei Patientinnen mit lokal fortgeschrittenem Brustkrebs und neoadjuvanter Chemotherapie besteht.

Material und Methoden In der Studie wurden kontrastverstärkte Ultraschallbilder von 43 Patientinnen mit Brustkrebs vor und nach neoadjuvanter Chemotherapie retrospektiv analysiert. Die Nachbearbeitung nach der Aufnahme umfasste die Festlegung von freihändig gezeichneten Regions of Interest (ROI), gefolgt von der Erstellung von Blutfluss-Kinetiken, die das Blutvolumen und die Flussgeschwindigkeit in diesen ROI abbilden. Qualitative und quantitative Parameter des kontrastverstärkten Ultraschalls wurden verglichen, um ein Rezidiv vorherzusagen, und eine ROC-Analyse (ROC: Receiver operating characteristics) wurde zur Bewertung der Vorhersagekraft angewandt.

Ergebnisse Von den 43 Patientinnen hatten 10 (23%) ein Krankheitsrezidiv (Median [Bereich]: 27 [4–68] Monate). Zwischen der Gruppe ohne Rezidiv und der Gruppe mit Rezidiv zeigte sich ein Unterschied in Bezug auf das Peak-Enhancement nach neoadjuvanter Chemotherapie (p=0,003), der Fläche unter der Kurve (AUC) des Wash-in (p=0,004), der AUC des Wash-out (p=0,026) und der AUC des Wash-in und Wash-out (p=0,014). Der Ultraschallparameter Fläche unter der ROC-Kurve war für das Peak-Enhancement nach neoadjuvanter Chemotherapie am höchsten (0,88; 95%-Konfidenzintervall: 0,75–1,00) mit einem Cut-off von 13,33 arbiträren Einheiten.

Schlussfolgerung Ein höheres Peak-Enhancement im kontrastverstärkten Ultraschall nach neoadjuvanter Chemotherapie war bei Frauen mit lokal fortgeschrittenem Brustkrebs mit einem Rezidiv assoziiert und stellt einen potenziellen Biomarker für ein Tumorrezidiv dar.

Keywords

Breast - Tumor recurrence - Neoadjuvant chemotherapy

Publication History

Received: 22 September 2023

Accepted after revision: 27 May 2024

Accepted Manuscript online:
27 May 2024

Article published online:
24 June 2024

• References

• 1 Lee ME, Kim SH, Kang BJ. et al. Contrast-Enhanced Ultrasound Parameters in Breast Cancer: Correlations with Prognostic Factors. J Korean Soc Radiol 2019; 80: 318-332
• 2 Sharma A, Grover SB, Mani C. et al. Contrast enhanced ultrasound quantitative parameters for assessing neoadjuvant chemotherapy response in patients with locally advanced breast cancer. Br J Radiol 2021; 94: 20201160
• 3 Clarke M, Collins R, Darby S. et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 366: 2087-2106
• 4 Spring LM, Fell G, Arfè A. et al. Pathologic complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: a comprehensive meta-analysis. Clin Cancer Res 2020; 26: 2838-2848
• 5 Kemperman H, Borger J, Hart A. et al. Prognostic factors for survival after breast conserving therapy for stage I and II breast cancer. The role of local recurrence. Eur J Cancer 1995; 31A: 690-698
• 6 Houssami N, Ciatto S, Martinelli F. et al. Early detection of second breast cancers improves prognosis in breast cancer survivors. Ann Oncol 2009; 20: 1505-1510
• 7 Lee YJ, Kim SH, Kang BJ. et al. Contrast-Enhanced Ultrasound for Early Prediction of Response of Breast Cancer to Neoadjuvant Chemotherapy. Ultraschall in Med 2019; 40: 194-204
• 8 Lawrence LI. A concordance correlation coefficient to evaluate reproducibility. Biometrics 1989; 45: 255-268
• 9 Fluss R, Faraggi D, Reiser B. Estimation of the Youden Index and its associated cutoff point. Biom J 2005; 47: 458-472
• 10 Wan C, Zhou L, Li H. et al. Multiparametric contrast-enhanced ultrasound in early prediction of response to neoadjuvant chemotherapy and recurrence-free survival in breast cancer. Diagnostics (Basel) 2023; 13: 2378
• 11 Jia K, Li L, Wu XJ. et al. Contrast-enhanced ultrasound for evaluating the pathologic response of breast cancer to neoadjuvant chemotherapy: A meta-analysis. Medicine (Baltimore) 2019; 98: e14258
• 12 Saracco A, Szabó BK, Tánczos E. et al. Contrast-enhanced ultrasound (CEUS) in assessing early response among patients with invasive breast cancer undergoing neoadjuvant chemotherapy. Acta Radiol 2017; 58: 394-402
• 13 Wan CF, Liu XS, Wang L. et al. Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy. Eur J Radiol 2018; 103: 118-123
• 14 Nam SY, Ko ES, Lim Y. et al. Preoperative dynamic breast magnetic resonance imaging kinetic features using computer-aided diagnosis: association with survival outcome and tumor aggressiveness in patients with invasive breast cancer. PLoS One 2018; 13: e0195756
• 15 Yi A, Cho N, Im SA. et al. Survival outcomes of breast cancer patients who receive neoadjuvant chemotherapy: association with dynamic contrast-enhanced MR imaging with computer-aided evaluation. Radiology 2013; 268: 662-72
• 16 Garcia Vicente A.M, Amo-Salas M, Relea-Calatayud F. et al. Prognostic role of early and end-of neoadjuvant treatment 18F-FDG PET/CT in patients with breast cancer. Clin. Nucl. Med 2016; 41: e313-e322
• 17 Hillaert A, Stock E, Favril S. et al. Intra- and inter-observer variability of quantitative parameters used in contrast-enhanced ultrasound of kidneys of healthy cats. Animals (Basel) 2022; 12: 3557
• 18 Kim JY, Kim SH, Kim YJ. et al. Enhancement parameters on dynamic contrast enhanced breast MRI: Do they correlate with prognostic factors and subtypes of breast cancers?. Magn Reson Imaging 2015; 33: 72-80
• 19 Choi EJ, Choi H, Choi SA. et al. Dynamic contrast-enhanced breast magnetic resonance imaging for the prediction of early and late recurrences in breast cancer. Medicine (Baltimore) 2016; 95: e5330
• 20 Kunz P, Kiesl S, Groß S. et al. Intra-observer and device-dependent inter-observer reliability of contrast-enhanced ultrasound for muscle perfusion quantification. Ultrasound Med Biol 2020; 46: 275-285
• 21 Schellhaas B, Pfeifer L, Kielisch C. et al. Interobserver Agreement for Contrast-Enhanced Ultrasound (CEUS)-Based Standardized Algorithms for the Diagnosis of Hepatocellular Carcinoma in High-Risk Patients. Ultraschall in Med 2018; 39: 667-674
• 22 Münch F, Silivasan EIE, Spiesecke P. et al. Intra- and Interobserver Study Investigating the Adapted EFSUMB Bosniak Cyst Categorization Proposed for Contrast-Enhanced Ultrasound (CEUS) in 2020. Ultraschall in Med 2024; 45: 47-53
• 23 Metzger-Filho O, Sun Z, Viale G. et al. Patterns of recurrence and outcome according to breast cancer subtypes in lymph node–negative disease: results from International Breast Cancer Study Group Trials VIII and IX. J Clin Oncol 2013; 31: 3083-3090
• 24 Tang S, Wang K, Zheng K. et al. Clinical and pathological response to neoadjuvant chemotherapy with different chemotherapy regimens predicts the outcome of locally advanced breast cancer. Gland Surg 2020; 9: 1415-1427
• 25 Bray F, Ferlay J, Soerjomataram I. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424
• 26 Weidner N, Semple JP, Welch WR. et al. Tumor angiogenesis and metastasis – correlation in invasive breast carcinoma. N Engl J Med 1991; 324: 1-8
• 27 Drudi FM, Cantisani V, Gnecchi M. et al. Contrast-enhanced ultrasound examination of the breast: A literature review. Ultraschall in Med 2012; 33: E1-E7