Marking of cytology-proven metastatic axillary lymph node in breast cancer patients before neoadjuvant treatment and its subsequent surgical retrieval have been shown to reduce the false-negative rate of sentinel lymph node biopsy. A systematic review was performed to evaluate different strategies in nodal marking and localization.
PubMed, Embase, EBSCOhost, and the Cochrane library literature databases were searched systematically to address the identification rate and retrieval rate of marked axillary lymph nodes. Studies were eligible if they performed nodal marking before neoadjuvant treatment, followed by selective extirpation of these marked axillary lymph nodes in definitive surgery
Fifteen studies with a total of 703 patients were included. Index axillary lymph nodes were marked by clips or tattooed prior to the commencement of neoadjuvant treatment. In our pooled analysis, eighty-eight percent of the clipped nodes and ninety-seven percent of the tattooed nodes were successfully retrieved. Among these patients, seventy-seven percent of these marked axillary lymph nodes were also sentinel lymph nodes.
Marking and selectively removing cytology-proven metastatic axillary lymph nodes after neoadjuvant treatment is feasible. An acceptably high nodal retrieval rate could be achieved using various methods of nodal marking and localization techniques.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Murphy BL, Day CN, Hoskin TL et al (2018) Neoadjuvant Chemotherapy Use in Breast Cancer is Greatest in Excellent Responders: Triple-Negative and HER2+ Subtypes. Ann Surg Oncol 25:2241–2248
Thompson AM, Moulder-Thompson SL et al (2012) Neoadjuvant chemotherapy of breast cancer. Ann Oncol 23:x231–x236
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2018) Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncology. 19:27–39
Pilewskie M, Morrow M (2017) Axillary nodal management following neoadjuvant chemotherapy. JAMA Oncology 3(4):549–555
Von Minckwitz G, Untch M, Blohmer JU et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30(15):1796–1804
Cortazar P, Zhang L, Untch M et al (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384(9938):164–172
Kuehn T, Bauerfeind I, Fehm T et al (2013) Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncology 14:609–618
Boileau JF, Poirier B, Basik M et al (2015) Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC Study. J Clin Oncol 33:258–264
Boughey JC, Suman VJ, Mittendorf EA et al (2013) Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: The American College of Surgeons Oncology Group (ACOSOG) Z1071 Clinical Trial. JAMA 310(4):1455–1461
El Hage CH, Headon H, El Tokhy O et al (2016) Is sentinel lymph node biopsy a viable alternative to complete axillary dissection following neoadjuvant chemotherapy in women with node-positive breast cancer at diagnosis? An updated meta-analysis involving 3,398 patients. Am J Surg 212(5):969–981
Boughey JC, Ballman KV, Le-Petross HT et al (2016) Identification and resection of the clipped node decreases the false negative rate of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0–T4, N1–2) who receive neoadjuvant chemotherapy - results from ACOSOG Z1071 (Alliance). Ann Surg 263(4):802–807
Caudle AS, Yang WT, Mittendorf EA et al (2015) Selective surgical localization of axillary lymph nodes containing metastases in patients with breast cancer: a prospective feasibility trial. JAMA Surgery 150(2):137–143
Caudle AS, Yang WT, Krishnamurthy S et al (2016) 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 34:1072–1078
National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology, Breast Cancer. Version 4.2020. www.nccn.org. [Accessed 18 August 2020].
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP et al (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370:1453–1457
Coufal O, Zapletal O, Gabrielová L, Fabian P, Schneiderová M (2018) Targeted axillary dissection and sentinel lymph node biopsy in breast cancer patients after neoadjuvant chemotherapy - a retrospective study. Cílenáaxilárnídisekce a sentinelovábiopsie u pacientek s karcinomemprsuponeoadjuvantníchemoterapii - retrospektivnístudie. RozhlChir. 97(12):551–557
Trinh L, Miyake KK, Dirbas FM et al (2016) CT-Guided Wire Localization for Involved Axillary Lymph Nodes After Neo-adjuvant Chemotherapy in Patients With Initially Node-Positive Breast Cancer. Breast J 22(4):390–396
Choy N, Lipson J, Porter C et al (2015) Initial results with preoperative tattooing of biopsied axillary lymph nodes and correlation to sentinel lymph nodes in breast cancer patients. Ann Surg Oncol 22(2):377–382
van Nijnatten TJA, Simons JM, Smidt ML et al (2017) 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. Clinical Breast Cancer 17:399–402
Donker M, Straver ME, Wesseling J et al (2015) Marking axillary lymph nodes with radioactive iodine seeds for axillary staging after neoadjuvant systemic treatment in breast cancer patients: the MARI procedure. Ann Surg 261(2):378–382
Hartmann S, Reimer T, Gerber B, Stubert J, Stengel B, Stachs A (2018) Wire localization of clip-marked axillary lymph nodes in breast cancer patients treated with primary systemic therapy. Eur J Surg Oncol 44(9):1307–1311
Kim EY, Byon WS, Lee KH et al (2018) Feasibility of Preoperative Axillary Lymph Node Marking with a Clip in Breast Cancer Patients Before Neoadjuvant Chemotherapy: A Preliminary Study. World J Surg 42(2):582–589
Siso C, de Torres J, Esgueva-Colmenarejo A et al. Intraoperative ultrasound-guided excision of axillary clip on 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. Annals of Surgical Oncology. 2018; 25: 784–791
Wu S, Wang Y, Zhang N et al (2018) Intraoperative touch imprint cytology in targeted axillary dissection after neoadjuvant chemotherapy for breast cancer patients with initial axillary metastasis. Ann Surg Oncol 25:3150–3157
Kanesalingam K, Sriram N, Heilat G et al (2020) Targeted axillary dissection after neoadjuvant systemic therapy in patients with node-positive breast cancer. ANZ J Surg 90(3):332–338
Flores-Funes D, Aguilar-Jimenez J, Martinez-Galvez M et al (2019) Validation of the targeted axillary dissection technique in the axillary staging of breast cancer after neoadjuvant therapy: preliminary results. Surg Oncol 30:52–57
Park S, Koo JS, Kim GM et al (2018) Feasibility of charcoal tattooing of cytology-proven metastatic axillary lymph node at diagnosis and sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer patients. Cancer Res Treat 50(3):801–812
Allweis TM, Menes T, Rotbart N et al (2020) 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 46(6):1041–1045
Patel R, MacKerricher W, Tsai J et al (2019) Pretreatment tattoo marking of suspicious axillary lymph nodes: reliability and correlation with sentinel lymph node. Ann SurgOncol 26(8):2452–2458
Plecha D, Bai S, Patterson H, Thompson C, Shenk R (2015) Improving the accuracy of axillary lymph node surgery in breast cancer with ultrasound-guided wire localization of biopsy proven metastatic lymph nodes. Ann SurgOncol 22(13):4241–4246
Diego EJ, McAuliffe PF, Soran A et al (2016) Axillary staging after neoadjuvant chemotherapy for breast cancer: a pilot study combining sentinel lymph node biopsy with radioactive seed localization of pre-treatment positive axillary lymph nodes. Ann SurgOncol 23(5):1549–1553
Nguyen TT, Hieken TJ, Glazebrook KN, Boughey JC (2017) Localizing the clipped node in patients with node-positive breast cancer treated with neoadjuvant chemotherapy: early learning experience and challenges. Ann SurgOncol 24(10):3011–3016
Balasubramanian R, Morgan C, Shaari E et al (2020) 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 46(6):1028–1033
Natsiopoulos I, Intzes S, Liappis T et al (2019) Axillary lymph node tattooing and targeted axillary dissection in breast cancer patients who presented as cN+ before neoadjuvant chemotherapy and became cN0 after treatment. Clinical Breast Cancer 19(3):208–215
Caudle AS, Yang WT, Krishnamurthy S et al (2016) 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 34(10):1072–1078
Straver ME, Loo CE, Alderliesten T, Rutgers EJ, Vrancken Peeters MT (2010) Marking the axilla with radioactive iodine seeds (MARI procedure) may reduce the need for axillary dissection after neoadjuvant chemotherapy for breast cancer. Br J Surg 97(8):1226–1231
Gobardhan PD, de Wall LL, van der Laan L, ten Tije AJ, van der Meer DC, Tetteroo E, Poortmans PM, Luiten EJ (2013) The role of radioactive iodine-125 seed localization in breast-conserving therapy following neoadjuvant chemotherapy. Ann Oncol 24(3):668–673
Pavlicek W, Walton HA, Karstaedt PJ, Gray RJ (2006) Radiation safety with use of I-125 seeds for localization of nonpalpable breast lesions. Acad Radiol 13(7):909–915
Goudreau SH, Joseph JP, Seiler SJ (2015) Preoperative radioactive seed localization for nonpalpable breast lesions: technique, pitfalls, and solutions. Radiographics. 35(5):1319–1334
Rissanen TJ, Mäkäräinen HP, Mattila SI, Karttunen AI, Kiviniemi HO, Kallioinen MJ, Kaarela OI (1993) Wire localized biopsy of breast lesions: a review of 425 cases found in screening or clinical mammography. Clin Radiol 47(1):14–22
Greenwood HI, Wong JM, Mukhtar RA, Alvarado MD, Price ER (2019) Feasibility of magnetic seeds for preoperative localization of axillary lymph nodes in breast cancer treatment. AJR Am J Roentgenol 213(4):953–957
García-Moreno JL, Benjumeda-Gonzalez AM, Amerigo-Góngora M, Landra-Dulanto PJ, Gonzalez-Corena Y, Gomez-Menchero J (2019) (2019) Targeted axillary dissection in breast cancer by marking lymph node metastasis with a magnetic seed before starting neoadjuvant treatment. J Surg Case Rep 11:344. https://doi.org/10.1093/jscr/rjz344
Taback B, Jadeja P, Ha R (2018) Enhanced axillary evaluation using reflector-guided sentinel lymph node biopsy: a prospective feasibility study and comparison with conventional lymphatic mapping techniques. Clin Breast Cancer 18(5):e869–e874
Falcon S, Weinfurtner RJ, Mooney B, Niell BL (2018) SAVI SCOUT® localization of breast lesions as a practical alternative to wires: Outcomes and suggestions for trouble-shooting. Clin Imaging. 52:280–286
The authors received no funding for the study.
Conflict of interest
All authors declare that they have no conflict of interest.
This article does not contain any studies with human participants performed by any of the authors.
Informed consent was obtained from the selected studies.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Man, V., Kwong, A. Different strategies in marking axillary lymph nodes in breast cancer patients undergoing neoadjuvant medical treatment: a systematic review. Breast Cancer Res Treat (2021). https://doi.org/10.1007/s10549-021-06118-6
- Breast cancer
- Neoadjuvant therapy
- Nodal marking
- Targeted axillary dissection