Subscribe to RSS
AGO Recommendations for the Surgical Therapy of the Axilla After Neoadjuvant Chemotherapy: 2021 UpdateArticle in several languages: English | deutsch
For many decades, the standard procedure to treat breast cancer included complete dissection of the axillary lymph nodes. The aim was to determine histological node status, which was then used as the basis for adjuvant therapy, and to ensure locoregional tumour control. In addition to the debate on how to optimise the therapeutic strategies of systemic treatment and radiotherapy, the current discussion focuses on improving surgical procedures to treat breast cancer. As neoadjuvant chemotherapy is becoming increasingly important, the surgical procedures used to treat breast cancer, whether they are breast surgery or axillary dissection, are changing. Based on the currently available data, carrying out SLNE prior to neoadjuvant chemotherapy is not recommended. In contrast, surgical axillary management after neoadjuvant chemotherapy is considered the procedure of choice for axillary staging and can range from SLNE to TAD and ALND. To reduce the rate of false negatives during surgical staging of the axilla in pN+CNB stage before NACT and ycN0 after NACT, targeted axillary dissection (TAD), the removal of > 2 SLNs (SLNE, no untargeted axillary sampling), immunohistochemistry to detect isolated tumour cells and micro-metastases, and marking positive lymph nodes before NACT should be the standard approach. This most recent update on surgical axillary management describes the significance of isolated tumour cells and micro-metastasis after neoadjuvant chemotherapy and the clinical consequences of low volume residual disease diagnosed using SLNE and TAD and provides an overview of this yearʼs AGO recommendations for surgical management of the axilla during primary surgery and in relation to neoadjuvant chemotherapy.
Received: 21 April 2021
Accepted after revision: 04 May 2021
06 October 2021 (online)
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
- 1 Ditsch N, Kolberg-Liedtke C, Friedrich M. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2021. Breast Care (Basel) 2021; 16: 214-227 DOI: 10.1159/000516419.
- 2 Kühn T, Klauss W, Darsow M. et al. Long-term morbidity following axillary dissection in breast cancer patients – clinical assessment, significance for life quality and the impact of demographic, oncologic and therapeutic factors. Breast Cancer Res Treat 2000; 64: 275-286
- 3 Krag DN, Anderson SJ, Julian TB. et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol 2010; 11: 927-933
- 4 Giuliano AE, Ballman KV, McCall L. et al. 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. JAMA 2017; 318: 918-926
- 5 Donker M, van Tienhoven G, Straver ME. et al. 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
- 6 Ditsch N, Untch M, Kolberg-Liedtke C. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2020. Breast Care (Basel) 2020; 15: 294-309 DOI: 10.1159/000508736.
- 7 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Mammakarzinoms, Version 4.3, 2020 AWMF Registernummer: 032–045OL. Online (Stand: 04.04.2021): http://www.leitlinienprogramm-onkologie.de/leitlinien/mammakarzinom/
- 8 NCCN. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Breast Cancer, Version 3.2021 – March 29, 2021. Online (Stand: 04.04.2021): https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419
- 9 Cardoso F, Kyriakides S, Ohno S. et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019; 30: 1194-1220 DOI: 10.1093/annonc/mdz173.
- 10 Boughey J, Suman V, Mittendorf E. et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA 2013; 310: 1455-1461
- 11 Kuehn T, Bauerfeind I, Fehm T. et al. Sentinel-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicenter cohort study. Lancet Oncol 2013; 14: 609-618
- 12 Caudle AS, Wang WT, Krishnamurthy S. et al. Improved Axillary Evaluation after Neoadjuvant Chemotherapy for Patients with Node-Positive Breast Cancer using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection. J Clin Oncol 2016; 34: 1072-1078
- 13 Banys-Paluchowski M, Gasparri ML, Boniface J. et al. Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03. Cancers 2021; 13: 1565 DOI: 10.3390/cancers13071565.
- 14 Banys-Paluchowski M, Gruber IV, Hartkopf A. et al. Axillary ultrasound for prediction of response to neoadjuvant therapy in the context of surgical strategies to axillary dissection in primary breast cancer: a systematic review of the current literature. Arch Gyn Obstet 2020; 301: 341-353 DOI: 10.1007/s00404-019-05428-x.
- 15 Kümmel S, Heil J, Rueland A. et al. Prospective, Multicenter Registry Study to Evaluate the Clinical Feasibility of Targeted Axillary Dissection (TAD) in Node-Positive Breast Cancer Patients. Ann Surg 2020; DOI: 10.1097/SLA.0000000000004572.
- 16 van Nijnatten TJA, Simons JM, Smidt ML. et al. A Novel Less-invasive Approach for Axillary Staging After Neoadjuvant Chemotherapy in Patients With Axillary Node-positive Breast Cancer by Combining Radioactive Iodine Seed Localization in the Axilla With the Sentinel Node Procedure (RISAS): A Dutch Prospective Multicenter Validation Study. Clin Breast Cancer 2017; 17: 399-402 DOI: 10.1016/j.clbc.2017.04.006.
- 17 Simons J, Nijnatten TJV, Koppert LB. et al. Radioactive Iodine Seed placement in the Axilla with Sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer: Results of the prospective multicenter RISAS trial. Gen Sess Abstr 2021; 81: GS1-10
- 18 Hartmann S, Kühn T, de Boniface J. et al. Carbon tattooing for targeted lymph node biopsy after primary systemic therapy in breast cancer: prospective multicentre TATTOO trial. Br J Surg 2021; DOI: 10.1093/bjs/znaa083.
- 19 Untch M, Jackisch C, Schneeweiss A. et al. NAB – Paclitaxel Improves Disease Free Survival in Early Breast Cancer: GBG 69 – GeparSepto. J Clin Oncol 2019; DOI: 10.1200/JCO.18.01842.
- 20 Boughey J, McCall L, Ballman K. et al. Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from ACOSOG Z1071 (Alliance) Prospective Multicenter Clinical Trial. Ann Surg 2014; 260: 608-614
- 21 Wong SM, Weiss A, Mittendorf EA. et al. Surgical Management of the Axilla in Clinically Node-Positive Patients Receiving Neoadjuvant Chemotherapy: A National Cancer Database Analysis. Ann Surg Oncol 2019; DOI: 10.1245/s10434-019-07583.
- 22 Hartmann S, Reimer T, Gerber B. et al. Wire localization of clip-marked axillary lymph nodes in breast cancer patients treated with primary systemic treatment. Eur J Surg Oncol 2018; 34: 1072-1078
- 23 Siso C, de Torres J, Esgueva-Colmenarejo A. et al. Intraoperative Ultrasound-Guided Excision of Axillary Clip in Patients with Node-Positive Breast Cancer Treated with Neoadjuvant Therapy (ILINA Trial): A New Tool to Guide the Excision of the Clipped Node After Neoadjuvant Treatment. Ann Surg Oncol 2018; 25: 784-791
- 24 Hanna TP, King WD, Thibodeau S. et al. Mortality due to cancer treatment delay: systematic review and meta-analysis. BMJ 2020; 371: m4087
- 25 Cone EB, Marchese M, Paciotti M. et al. Assessment of Time-to-Treatment Initiation and Survival in a Cohort of Patients With Common Cancers. JAMA Netw Open 2020; 3: e2030072 DOI: 10.1001/jamanetworkopen.2020.30072.
- 26 Reimer T, Gerber B. Quality-of-life considerations in the treatment of early-stage breast cancer in the elderly. Drugs Aging 2010; 27: 791-800
- 27 Tuttle TM, Shamliyan T, Virnig BA. et al. The impact of sentinel lymph node biopsy and magnetic resonance imaging on important outcomes among patients with ductal carcinoma in situ. J Natl Cancer Inst Monogr 2010; 2010: 117-120
- 28 Gerber B, Heintze K, Stubert J. et al. Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today?. Breast Cancer Res Treat 2011; 128: 613-624
- 29 DʼAngelo-Donovan DD, Dickson-Witmer D, Petrelli NJ. Sentinel lymph node biopsy in breast cancer: A history and current clinical recommendations. Surg Oncol 2012; 21: 196-200
- 30 Galimberti V, Cole BF, Zurrida S. et al. International Breast Cancer Study Group Trial 23-01 investigators. 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
- 31 Giuliano AE, Ballman KV, McCall L. et al. 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. JAMA 2017; 318: 918-926
- 32 Fu JF, Chen HL, Yang J. et al. Feasibility and accuracy of sentinel lymph node biopsy in clinically node-positive breast cancer after neoadjuvant chemotherapy: a meta-analysis. PLoS One 2014; 9: e105316
- 33 Lee HD, Ahn SG, Lee SA. et al. Prospective Evaluation of the Feasibility of Sentinel Lymph Node Biopsy in Breast Cancer Patients with Negative Axillary Conversion after Neoadjuvant Chemotherapy. Cancer Res Treat 2014; DOI: 10.4143/crt.2013.208.
- 34 Boileau JF, Poirier B, Basik M. et al. Sentinel Node Biopsy After Neoadjuvant Chemotherapy in Biopsy-Proven Node-Positive Breast Cancer: The SN FNAC Study. J Clin Oncol 2015; 33: 258-264
- 35 Boughey JC, Ballman KV, Le-Petross HT. et al. 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; 263: 802-807
- 36 Ryu JM, Lee SK, Kim JY. et al. Predictive Factors for Nonsentinel Lymph Node Metastasis in Patients With Positive Sentinel Lymph Nodes After Neoadjuvant Chemotherapy: Nomogram for Predicting Nonsentinel Lymph Node Metastasis. Clin Breast Cancer 2017; 17: 550-555
- 37 Galimberti V, Ribeiro Fontana SK, Maisonneuve P. Sentinel node biopsy after neoadjuvant treatment in breast cancer: five-year follow-up of patients with clinically node-negative or node-positive disease before treatment. Eur J Surg Oncol 2016; 42: 361-368
- 38 Martelli G, Miceli R, Folli S. et al. Sentinel node biopsy after primary chemotherapy in cT2 N0/1 breast cancer patients: Long-term results of a retrospective study. Eur J Surg Oncol 2017; 43: 2012-2020
- 39 Palmer JAV, Flippo-Morton T, Walsh KK. et al. Application of ACOSOG Z1071: Effect of Results on Patient Care and Surgical Decision-Making. Clin Breast Cancer 2018; 18: 270-275 DOI: 10.1016/j.clbc.2017.10.006.
- 40 Fernandez-Gonzalez S, Falo C, Pla MJ. et al. The Shift From Sentinel Lymph Node Biopsy Performed Either Before or After Neoadjuvant Systemic Therapy in the Clinical Negative Nodes of Breast Cancer Patients. Results, and the Advantages and Disadvantages of Both Procedures. Clin Breast Cancer 2018; 18: 71-77 DOI: 10.1016/j.clbc.2017.08.014.
- 41 Kahler-Ribeiro-Fontana S, Pagan E, Magnoni F. et al. 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
- 42 Tee SR, Devane LA, Evoy D. et al. Meta-analysis of sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with initial biopsy-proven node-positive breast cancer. Br J Surg 2018; 105: 1541-1552
- 43 Balic M, Thomssen C, Würstlein R. et al. St. Gallen/Vienna 2019: A Brief Summary of the Consensus Discussion on the Optimal Primary Breast Cancer Treatment. Breast Care (Basel) 2019; 14: 103-110
- 44 Classe JM, Loaec C, Gimbergues P. et al. Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for selected patients: the GANEA 2 study. Breast Cancer Res Treat 2019; 173: 343-352
- 45 Moo TA, Edelweiss M, Hajiyeva S. et al. Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an Indication for Axillary Dissection?. Ann Surg Oncol 2018; 25: 1488-1494 Erratum in: Ann Surg Oncol 2020; 27 (Suppl. 3): 966 Erratum in: Ann Surg Oncol 2020; 27 (Suppl. 3): 966
- 46 Allweis TM, Menes T, Rotbart N. et al. Ultrasound guided tattooing of axillary lymph nodes in breast cancer patients prior to neoadjuvant therapy, and identification of tattooed nodes at the time of surgery. Eur J Surg Oncol 2020; 46: 1041-1045 DOI: 10.1016/j.ejso.2019.11.501.
- 47 Balasubramian R, Morgan C, Shaari E. et al. Wire guided localisation for targeted axillary node dissection is accurate in axillary staging in node positive breast cancer following neoadjuvant chemotherapy. Eur J Surg Oncol 2020; 46: 1028-1033 DOI: 10.1016/j.ejso.2019.12.007.
- 48 Coufal O, Zapletal O, Gabrielová L. et al. Targeted axillary dissection and sentinel lymph node biopsy in breast cancer patients after neoadjuvant chemotherapy – a retrospective study. Rozhl Chir Winter 2018; 97: 551-557
- 49 Ditsch N, Rubio IT, Gasparri ML. et al. Breast and axillary surgery in malignant breast disease: a review focused on literature of 2018 and 2019. Curr Opin Obstet Gynecol 2020; 32: 91-99
- 50 Flores-Funes D, Aguilar-Jiménez J, Martínez-Gálvez M. et al. Validation of the targeted axillary dissection technique in the axillary staging of breast cancer after neoadjuvant therapy: Preliminary results. Surg Oncol 2019; 30: 52-57 DOI: 10.1016/j.suronc.2019.05.019.
- 51 Gandhi A, Coles C, Makris A. et al. Axillary Surgery Following Neoadjuvant Chemotherapy – Multidisciplinary Guidance From the Association of Breast Surgery, Faculty of Clinical Oncology of the Royal College of Radiologists, UK Breast Cancer Group, National Coordinating Committee for Breast Pathology and British Society of Breast Radiology. Clin Oncol (R Coll Radiol) 2019; 31: 664-668
- 52 García-Moreno JL, Benjumeda-Gonzalez AM, Amerigo-Góngora M. et al. Targeted axillary dissection in breast cancer by marking lymph node metastasis with a magnetic seed before starting neoadjuvant treatment. J Surg Case Rep 2019; 2019: rjz344
- 53 Greenwood HI, Wong JM, Mukhtar RA. et al. Feasibility of Magnetic Seeds for Preoperative Localization of Axillary Lymph Nodes in Breast Cancer Treatment. AJR Am J Roentgenol 2019; 213: 953-957
- 54 Hellingman D, Donswijk ML, Winter-Warnars GAO. et al. Feasibility of radioguided occult lesion localization of clip-marked lymph nodes for tailored axillary treatment in breast cancer patients treated with neoadjuvant systemic therapy. EJNMMI Res 2019; 9: 94
- 55 Kanesalingam K, Sriram N, Heilat G. et al. Targeted axillary dissection after neoadjuvant systemic therapy in patients with node-positive breast cancer. ANZ J Surg 2020; 90: 332-338 DOI: 10.1111/ans.15604.
- 56 Natsiopoulos I, Intzes S, Liappis T. et al. Axillary Lymph Node Tattooing and Targeted Axillary Dissection in Breast Cancer Patients Who Presented as cN+ Before Neoadjuvant Chemotherapy and Became cN0 After Treatment. Clin Breast Cancer 2019; 19: 208-215
- 57 Simons JM, van Nijnatten TJA, van der Pol CC. et al. Diagnostic Accuracy of Different Surgical Procedures for Axillary Staging After Neoadjuvant Systemic Therapy in Node-positive Breast Cancer: A Systematic Review and Meta-analysis. Ann Surg 2019; 269: 432-442
- 58 Simons JM, van Pelt MLMA, Marinelli AWKS. et al. Excision of both pretreatment marked positive nodes and sentinel nodes improves axillary staging after neoadjuvant systemic therapy in breast cancer. Br J Surg 2019; 106: 1632-1639
- 59 Lee J, Jung JH, Kim WW. et al. 5-year oncological outcomes of targeted axillary sampling in pT1-2N1 breast cancer. Asian J Surg 2019; 42: 681-687 DOI: 10.1016/j.asjsur.2018.10.004.
- 60 National Cancer Institute. Comparison of axillary lymph node dissection with axillary radiation for patients with node-positive breast cancer reated with chemotherapy. Online (Stand: 09.05.2015): http://www.cancer.gov/clinicaltrials/search/view?cdrid=751211&version=HealthProfessional