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Enhanced axillary assessment using intradermally injected microbubbles and contrast-enhanced ultrasound (CEUS) before neoadjuvant systemic therapy (NACT) identifies axillary disease missed by conventional B-mode ultrasound that may be clinically relevant

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Abstract

Purpose

The purpose of this study is to measure pre-treatment diagnostic yield of malignant lymph nodes (LN) using contrast-enhanced ultrasound (CEUS) in addition to B-mode axillary ultrasound and compare clinicopathological features, response to NACT and long-term outcomes of patients with malignant LN detected with B-mode ultrasound versus CEUS.

Methods

Between August 2009 and October 2016, NACT patients were identified from a prospective database. Follow-up data were collected until May 2019.

Results

288 consecutive NACT patients were identified; 77 were excluded, 110 had malignant LN identified by B-mode ultrasound (Group A) and 101 patients with negative B-mode axillary ultrasound had CEUS with biopsy of sentinel lymph nodes (SLN). In two cases CEUS failed. Malignant SLN were identified in 35/99 (35%) of B-mode ultrasound-negative cases (Group B). Patients in Group A were similar to those in Group B in age, mean diagnostic tumour size, grade and oestrogen receptor status. More Group A patients had a ductal phenotype. In the breast, 34 (31%) Group A patients and 8 (23%) Group B patients achieved a pathological complete response (PCR). In the axilla, 41 (37%) and 13 (37%) Groups A and B patients, respectively, had LN PCR. The systemic relapse rate was not statistically different (5% and 16% for Groups A and B, respectively).

Conclusions

Enhanced assessment with CEUS before NACT identifies patients with axillary metastases missed by conventional B-mode ultrasound. Without CEUS, 22 (63%) of cases in Group B (negative B-mode ultrasound) may have been erroneously classed as progressive disease by surgical SLN excision after NACT.

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Data availability

The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank the staff and patients at Maidstone and Tunbridge Wells Breast Unit for supporting this work.

Funding

This study did not require external funding as all costs were covered by Maidstone and Tunbridge Wells NHT Trust who also sponsored this study. The following authors are employees of Maidstone and Tunbridge Wells NHS Trust; Karina Cox, Nicky Dineen, Jennifer Weeks, Deborah Allen, Ritchie Chalmers, Deepika Akolekar, Russell Burcombe, Catherine Harper-Wynne and Rema Jyothirmayi.

Author information

Authors and Affiliations

  1. Peggy Wood Breast Unit, Maidstone Hospital, Hermitage Lane, Maidstone, Kent, ME16 9QQ, UK

    Karina Cox, Nicky Dineen, Deborah Allen, Jennifer Weeks, Ritchie Chalmers & Deepika Akolekar

  2. WMS-Population Evidence and Technologies, University of Warwick, Coventry, CV4 7AL, UK

    Sian Taylor-Phillips

  3. Leeds Breast Unit, St James’s University Hospital, Beckett Street, Leeds, LS9 7TF, UK

    Nisha Sharma

  4. Kent Oncology Centre, Maidstone Hospital, Hermitage Lane, Maidstone, Kent, ME16 9QQ, UK

    Catherine Harper-Wynne, Russell Burcombe & Rema Jyothirmayi

  5. Guy’s Breast Unit, Great Maze Pond, London, SE1 9RT, UK

    Ali Sever

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  1. Karina Cox
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Corresponding author

Correspondence to Karina Cox.

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Conflict of interest

All the authors certify that they have no affiliations with or involvement in any organisation or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in this study. Following a trial period (Kent REC Reference Numbers: 04/Q1801/25 and 11/H1101/1, Eudract Number: 2004-002423-41), on the 16th December 2011 the technique using intradermal microbubbles and CEUS to biopsy SLN in breast cancer patients was approved as a new clinical procedure by Maidstone and Tunbridge Wells NHS Trust and became part of the routine diagnostic pathway for patients diagnosed with breast cancer.

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Cox, K., Dineen, N., Taylor-Phillips, S. et al. Enhanced axillary assessment using intradermally injected microbubbles and contrast-enhanced ultrasound (CEUS) before neoadjuvant systemic therapy (NACT) identifies axillary disease missed by conventional B-mode ultrasound that may be clinically relevant. Breast Cancer Res Treat 185, 413–422 (2021). https://doi.org/10.1007/s10549-020-05956-0

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