Tailored axillary surgery in patients with clinically node-positive breast cancer: Pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101)

Walter P Weber, Zoltan Matrai, Stefanie Hayoz, Christoph Tausch, Guido Henke, Daniel R Zwahlen, Günther Gruber, Frank Zimmermann, Stefanie Seiler, Charlotte Maddox, Thomas Ruhstaller, Simone Muenst, Markus Ackerknecht, Sherko Kuemmel, Vesna Bjelic-Radisic, Christian Kurzeder, Mihály Újhelyi, Conny Vrieling, Rok Satler, Inna Meyer, Charles Becciolini, Susanne Bucher, Colin Simonson, Peter M Fehr, Natalie Gabriel, Robert Maráz, Dimitri Sarlos, Konstantin J Dedes, Cornelia Leo, Gilles Berclaz, Peter Dubsky, Ruth Exner, Hisham Fansa, Christopher Hager, Klaus Reisenberger, Christian F Singer, Roland Reitsamer, Mattea Reinisch, Jelena Winkler, Giang Thanh Lam, Mathias K Fehr, Tatiana Naydina, Magdalena Kohlik, Karine Clerc, Valerijus Ostapenko, Florian Fitzal, Rahel Nussbaumer, Nadia Maggi, Alexandra Schulz, Pagona Markellou, Loïc Lelièvre, Daniel Egle, Jörg Heil, Michael Knauer, Walter P Weber, Zoltan Matrai, Stefanie Hayoz, Christoph Tausch, Guido Henke, Daniel R Zwahlen, Günther Gruber, Frank Zimmermann, Stefanie Seiler, Charlotte Maddox, Thomas Ruhstaller, Simone Muenst, Markus Ackerknecht, Sherko Kuemmel, Vesna Bjelic-Radisic, Christian Kurzeder, Mihály Újhelyi, Conny Vrieling, Rok Satler, Inna Meyer, Charles Becciolini, Susanne Bucher, Colin Simonson, Peter M Fehr, Natalie Gabriel, Robert Maráz, Dimitri Sarlos, Konstantin J Dedes, Cornelia Leo, Gilles Berclaz, Peter Dubsky, Ruth Exner, Hisham Fansa, Christopher Hager, Klaus Reisenberger, Christian F Singer, Roland Reitsamer, Mattea Reinisch, Jelena Winkler, Giang Thanh Lam, Mathias K Fehr, Tatiana Naydina, Magdalena Kohlik, Karine Clerc, Valerijus Ostapenko, Florian Fitzal, Rahel Nussbaumer, Nadia Maggi, Alexandra Schulz, Pagona Markellou, Loïc Lelièvre, Daniel Egle, Jörg Heil, Michael Knauer

Abstract

Aim: We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of this study was to quantify the extent of tumor load reduction achieved by TAS.

Methods: International multicenter prospective study embedded in a randomized trial. TAS is a novel pragmatic concept for axillary surgery de-escalation that combines palpation-guided removal of suspicious nodes with the sentinel procedure and, optionally, imaging-guided localization. Pre-specified study endpoints quantified surgical extent and reduction of tumor load.

Results: A total of 296 patients were included at 28 sites in four European countries, 125 (42.2%) of whom underwent neoadjuvant chemotherapy (NACT) and 71 (24.0%) achieved nodal pathologic complete response. Axillary metastases were detectable only by imaging in 145 (49.0%) patients. They were palpable in 151 (51.0%) patients, of whom 63 underwent NACT and 21 had residual palpable disease after NACT. TAS removed the biopsied and clipped node in 279 (94.3%) patients. In 225 patients with nodal disease at the time of surgery, TAS removed a median of five (IQR 3-7) nodes, two (IQR 1-4) of which were positive. Of these 225 patients, 100 underwent ALND after TAS, which removed a median of 14 (IQR 10-17) additional nodes and revealed additional positive nodes in 70/100 (70%) of patients. False-negative rate of TAS in patients who underwent subsequent ALND was 2.6%.

Conclusions: TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND.

Keywords: Axillary dissection; Axillary staging; Breast cancer; Breast surgery; Sentinel lymph node procedure.

Conflict of interest statement

Declaration of interest statement Outside the submitted work, W.P. Weber received research support from Takeda Pharmaceuticals International paid to the Swiss Group for Clinical Cancer Research (SAKK) and personal honoraria from Genomic Health, Inc., USA. Support for meetings was paid to his institution from Sandoz, Genomic Health, Medtronic, Novartis Oncology, Pfizer and Eli Lilly. Hisham Fansa has no financial interest, and receives royalty payments from Springer-Nature publishers for two textbooks on breast surgery. Florian Fitzal was editor of Oncoplastic Surgery part I and II (SPRINGER), received travel support and scientific support from COMESA (Mentor), NOVARTIS, ROCHE, ASTRA ZENECA, PFIZER, MYRIAD, NANOSTRING, BONDIMED (Polytech, Integra), Lilly, had an advisory role for PFIZER, ASTRA ZENECA, LILLY, ROCHE, and was founder of BREAST ANALYZING TOOL (BAT; breastanalyzing.com). All other authors declare no competing interests relevant to this manuscript.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
The concept of tailored axillary surgery (TAS).
Fig. 2
Fig. 2
Study population by palpable versus non-palpable axillary disease.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/8463904/bin/fx1.jpg
Fig. A.1Pre-specified prospective study population embedded in TAXIS trial.

References

    1. Donker M., van T.G., Straver M.E. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15:1303–1310.
    1. Giuliano A.E., McCall L., Beitsch P. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg. 2010;252:426–432.
    1. Giuliano A.E., Hunt K.K., Ballman K.V. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. J Am Med Assoc. 2011;305:569–575.
    1. Galimberti V., Cole B.F., Zurrida S. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol. 2013;14:297–305.
    1. Savolt A., Peley G., Polgar C. Eight-year follow up result of the OTOASOR trial: the Optimal Treatment of the Axilla - surgery or Radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: a randomized, single centre, phase III, non-inferiority trial. Eur J Surg Oncol. 2017;43:672–679.
    1. Weber W.P., Barry M., Stempel M.M. A 10-year trend analysis of sentinel lymph node frozen section and completion axillary dissection for breast cancer: are these procedures becoming obsolete? Ann Surg Oncol. 2012;19:225–232.
    1. Boileau J.F., Poirier B., Basik M. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol. 2015;33:258–264.
    1. Boughey J.C., Ballman K.V., Le-Petross H.T. Identification and resection of clipped node decreases the false-negative rate of sentinel lymph node surgery in patients presenting with node-positive breast cancer (T0-T4, N1-N2) who receive neoadjuvant chemotherapy: results from ACOSOG Z1071 (alliance) Ann Surg. 2016 Apr;263(4):802–807.
    1. Kuehn T., Bauerfeind I., Fehm T. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14:609–618.
    1. Nguyen T.T., Hoskin T.L., Day C.N. Decreasing use of axillary dissection in node-positive breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2018;25:2596–2602.
    1. Laws A., Hughes M.E., Hu J. Impact of residual nodal disease burden on technical outcomes of sentinel lymph node biopsy for node-positive (cN1) breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2019;26:3846–3855.
    1. Mamtani A., Barrio A.V., King T.A. How often does neoadjuvant chemotherapy avoid axillary dissection in patients with histologically confirmed nodal metastases? Results of a prospective study. Ann Surg Oncol. 2016;23:3467–3474.
    1. Hieken T.J., Trull B.C., Boughey J.C. Preoperative axillary imaging with percutaneous lymph node biopsy is valuable in the contemporary management of patients with breast cancer. Surgery. 2013;154:831–838. discussion 838-40.
    1. Caudle A.S., Kuerer H.M., Le-Petross H.T. Predicting the extent of nodal disease in early-stage breast cancer. Ann Surg Oncol. 2014;21:3440–3447.
    1. Yoo T.K., Kang B.J., Kim S.H. Axillary lymph node dissection is not obligatory in breast cancer patients with biopsy-proven axillary lymph node metastasis. Breast Canc Res Treat. 2020;181:403–409.
    1. Lim G.H., Upadhyaya V.S., Acosta H.A. Preoperative predictors of high and low axillary nodal burden in Z0011 eligible breast cancer patients with a positive lymph node needle biopsy result. Eur J Surg Oncol. 2018;44:945–950.
    1. Ahmed M., Jozsa F., Baker R. Meta-analysis of tumour burden in pre-operative axillary ultrasound positive and negative breast cancer patients. Breast Canc Res Treat. 2017;166:329–336.
    1. Verheuvel N.C., Voogd A.C., Tjan-Heijnen V.C.G. Different outcome in node-positive breast cancer patients found by axillary ultrasound or sentinel node procedure. Breast Canc Res Treat. 2017;165:555–563.
    1. Pilewskie M., Mautner S.K., Stempel M. Does a positive axillary lymph node needle biopsy result predict the need for an axillary lymph node dissection in clinically node-negative breast cancer patients in the ACOSOG Z0011 era? Ann Surg Oncol. 2016;23:1123–1128.
    1. National Comprehensive Cancer Network . 2020. Guidelines breast cancer.
    1. Henke G., Knauer M., Ribi K. Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (TAXIS): study protocol for a multicenter, randomized phase-III trial. Trials. 2018;19 667.
    1. TNM classification of malignant tumours. eighth ed. UICC); Jan 2017.
    1. Bing A.U., Kerr G.R., Jack W. Pooled long-term outcomes from two randomized trials of axillary node sampling with axillary radiotherapy versus axillary node clearance in patients with operable node-positive breast cancer. Br J Surg. 2016;103:81–87.
    1. Ahlgren J., Holmberg L., Bergh J. Five-node biopsy of the axilla: an alternative to axillary dissection of levels I-II in operable breast cancer. Eur J Surg Oncol. 2002;28:97–102.
    1. Boughey J.C., Suman V.J., Mittendorf E.A. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. J Am Med Assoc. 2013;310:1455–1461.
    1. Giuliano A.E., Ballman K.V., McCall L. Effect of axillary dissection vs No axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (alliance) randomized clinical trial. J Am Med Assoc. 2017;318:918–926.
    1. Jagsi R., Chadha M., Moni J. Radiation field design in the ACOSOG Z0011 (alliance) trial. J Clin Oncol. 2014;32:3600–3606.
    1. Angarita S., Ye L., Runger D. Assessing the burden of nodal disease for breast cancer patients with clinically positive nodes: hope for more limited axillary surgery. Ann Surg Oncol. 2021;28:2609–2618.
    1. Fisher B., Jeong J.H., Anderson S. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347:567–575.
    1. Mittendorf E.A., Caudle A.S., Yang W. Implementation of the american college of surgeons oncology group z1071 trial data in clinical practice: is there a way forward for sentinel lymph node dissection in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy? Ann Surg Oncol. 2014;21:2468–2473.
    1. Kuemmel S., Heil J., Rueland A. A prospective, multicenter registry study to evaluate the clinical feasibility of targeted axillary dissection (TAD) in node-positive breast cancer patients. Ann Surg. 2020 Nov 4 Online ahead of print.
    1. Wong S.M., Basik M., Florianova L. Oncologic safety of sentinel lymph node biopsy alone after neoadjuvant chemotherapy for breast cancer. Ann Surg Oncol. 2021;28:2621–2629.
    1. Kahler-Ribeiro-Fontana S., Pagan E., Magnoni F. Long-term standard sentinel node biopsy after neoadjuvant treatment in breast cancer: a single institution ten-year follow-up. Eur J Surg Oncol. 2021;47:804–812.
    1. Damin A.P., Zancan M., Melo M.P. Sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with node-positive breast cancer: guiding a more selective axillary approach. Breast Canc Res Treat. 2021;186:527–534.
    1. Piltin M.A., Hoskin T.L., Day C.N. Oncologic outcomes of sentinel lymph node surgery after neoadjuvant chemotherapy for node-positive breast cancer. Ann Surg Oncol. 2020;27:4795–4801.
    1. Samiei S., de Mooij C.M., Lobbes M.B.I. Diagnostic performance of noninvasive imaging for assessment of axillary response after neoadjuvant systemic therapy in clinically node-positive breast cancer: a systematic review and meta-analysis. Ann Surg. 2021 Apr 1;273(4):694–700.
    1. Caudle A.S., Yang W.T., Krishnamurthy S. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol. 2016 Apr 1;34(10):1072–1078.
    1. Almahariq M.F., Levitin R., Quinn T.J. Omission of axillary lymph node dissection is associated with inferior survival in breast cancer patients with residual N1 nodal disease following neoadjuvant chemotherapy. Ann Surg Oncol. 2021;28:930–940.
    1. Burstein Gc H.J., Thürlimann B., Weber W.P., Poortmans P., Regan M., Senn H.J., Winer E.P. Customizing local and systemic therapies for women with early breast cancer: the St.Gallen International Consensus Guidelines for treatment of early breast cancer. 2021. M. Gnant and panelists of the St.Gallen consensus conference.

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