Evaluation of axillary response to neoadjuvant systemic therapy with sentinel node biopsy and axillary wire in node-positive breast cancer

Objective: To determine the safety and reliability of directed axillary dissection with sentinel node biopsy (SNB) and marked lymph node biopsy (MLNB) with axillary wire on the clipped node, for the selection of patients who are candidates for conservative axillary treatment after the diagnosis of node-positive breast cancer who show a complete axillary response after neoadjuvant treatment. Materials: A prospective cohort study was carried out at Miguel Servet University Hospital in Zaragoza. 66 patients with a diagnosis of breast cancer and initial histological axillary involvement were finally included, in which the biopsied node was marked with a titanium clip prior to the start of neoadjuvant treatment. All patients underwent axillary sampling using SNB or Targeted axillary dissection (TAD) by SNB and MLNB with axillary wire on the clipped node before performing lymphadenectomy. Results: The detection rate (DR) of the SNB was 100% with a mean of 1.8 sentinel nodes studied. In 14 patients, axillary sampling was performed only with SNB, with a false negative rate (FNR) of 14.29%, which decreased when 2 or more nodes were removed or when clipped node was removed. In 51 cases, double marking with SNB and MLNB with axillary wire was performed, which ensures excision of the clipped node in 96.1% of cases with a FNR of 1.96%. The negative predictive value (NPV) of the sample when the clipped node is studied was 96.8%. Conclusions: Targeted axillary dissection with SNB and MLNB with axillary wire on the clipped node is a safe and effective strategy for the selection of patients who are candidates for conservative axillary treatment after neoadjuvant treatment, avoiding unnecessary lymphadenectomies.

Node-positive breast cancer; Neoadjuvant systemic therapy; Sentinel node biopsy; Axillary wire; Lymphadenectomy

[1] Donker M, Straver ME, Wesseling J, Loo CE, Schot M, Drukker CA, et al. Marking axillary lymph nodes with radioactive Iodine seeds for axillary staging after neoadjuvant systemic treatment in breast cancer patients: the MARI procedure. Annals of Surgery. 2015; 261: 378–382.

[2] Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncology. 2018; 19: 27–39.

[3] Kim WH, Kim HJ, Park HY, Park JY, Chae YS, Lee SM, et al. Axillary Pathologic Complete Response to Neoadjuvant Chemother- apy in Clinically Node-Positive Breast Cancer Patients: a Predic- tive Model Integrating the Imaging Characteristics of Ultrasound Restaging with Known Clinicopathologic Characteristics. Ultra- sound in Medicine & Biology. 2019; 45: 702–709.

[4] Samiei S, Simons JM, Engelen SME, Beets-Tan RGH, Classe JM, Smidt ML. Axillary pathologic complete response after neoadjuvant systemic therapy by breast cancer subtype in patients with initially clinically node-positive disease: a systematic review and meta-analysis. JAMA Surgery. 2021; 156: e210891.

[5] Charalampoudis P, Markopoulos C, Kovacs T. Controversies and recommendations regarding sentinel lymph node biopsy in pri- mary breast cancer: a comprehensive review of current data. Eu- ropean Journal of Surgical Oncology. 2018; 44: 5–14.

[6] Kuru B. The adventure of axillary treatment in early stage breast cancer. European Journal of Breast Health 2020; 16: 1–15.

[7] Wazir U, Mokbel K. De-escalation of Axillary Surgery in the Neoadjuvant Chemotherapy (NACT) Setting for Breast Cancer: is it Oncologically Safe? Anticancer Research. 2020; 40: 5351–5354.

[8] Swarnkar PK, Tayeh S, Michell MJ, Mokbel K. The evolving role of marked lymph node biopsy (MLNB) and targeted axillary dissection (TAD) after neoadjuvant chemotherapy (NACT) for node-positive breast cancer: systematic review and pooled anal- ysis. Cancers. 2021; 13: 1539.

[9] Li Y, Zhou Y, Mao F, Lin Y, Zhang X, Shen S, et al. The diagnostic performance of minimally invasive biopsy in predicting breast pathological complete response after neoadjuvant systemic ther- apy in breast cancer: a meta-analysis. Frontiers in Oncology 2020; 10: 933.

[10] Simons JM, van Nijnatten TJA, van der Pol CC, Luiten EJT, Kop- pert LB, Smidt ML. Diagnostic Accuracy of Different Surgical Procedures for Axillary Staging after Neoadjuvant Systemic Therapy in Node-positive Breast Cancer. Annals of Surgery. 2019; 269: 432–442.

[11] Bossuyt V, Provenzano E, Symmans WF, Boughey JC, Coles C, Curigliano G, et al. Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical tri- als of breast cancer by the BIG-NABCG collaboration. Annals of Oncology. 2015; 26: 1280–1291.

[12] Tadros AB, Yang WT, Krishnamurthy S, Rauch GM, Smith BD, Valero V, et al. Identification of Patients with Documented Pathologic Complete Response in the Breast after Neoadjuvant Chemotherapy for Omission of Axillary Surgery. JAMA Surgery. 2017; 152: 665–670.

[13] Zetterlund LH, Frisell J, Zouzos A, Axelsson R, Hatschek T, de Boniface J, et al. Swedish prospective multicenter trial evaluating sentinel lymph node biopsy after neoadjuvant systemic therapy in clinically node-positive breast cancer. Breast Cancer Research and Treatment. 2017; 163: 103–110.

[14] Rockson SG. Lymphedema after Breast Cancer Treatment. New England Journal of Medicine. 2018; 379: 1937–1944.

[15] Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2019; 30: 1674.

[16] NCCN Clinical Practice Guidelines in Oncology, Breast Can- cer, Version 1.2021—15 January 2021. NCCN.org. 2021. Avail- able at: https://www.nccn.org/professionals/physician_gls/defau lt.aspx#breast (Accessed: 27 March 2021).

[17] Consensus Guideline on the Management of the Axilla in Patients with Invasive/In-Situ Breast Cancer. The American Society of Breast Surgeons. 2019. Available at: https://www.breastsurgeons.org/docs/statements/Consensus-G uideline-on-the-Management-of-the-Axilla.pdf?v2 (Accessed: 27 March 2021).

[18] Regionala cancercentrum i samverkan. Bröstcancer- Nationellt Vårdprogram-SweBCG, 2020. Available at: http://www.swebcg.se/wp-content/uploads/2016/10/nati onellt-vardprogram-brostcancer_200211.pdf (Accessed: 1 December 2020).

[19] Finnish Breast Cancer Group. Rintasyöpäryhmän Valtakun- nallinen Diagnostiikka—Ja Hoitosuositus. 2019. Available at: https://1587667.167.directo.fi/@Bin/c554c241df494d864925e 07ad6aa705e/1614023914/application/pdf/186425/SRSR_Suosi tus_2019%20Joulukuu.pdf (Accessed: 1 December 2019).

[20] Halberg AK, Gravesen CD, Cold S, Jensen JD. Neoadjuvant chemotherapy for primary operable breast cancer. Danish Med- ical Journal. 2020; 67: A01200010.

[21] Recommendations of the AGO Breast Committee: Diagnosis and Treatment of Patients with early and advanced Breast Can- cer. 2018. Available at: www.ago-online.de (Accessed: 27 March 2021).

[22] Ayala de la Peña F, Andrés R, Garcia-Sáenz JA, Manso L, Margelí M, Dalmau E, et al. SEOM clinical guidelines in early stage breast cancer (2018). Clinical and Translational Oncology. 2019; 21: 18– 30.

[23] Boughey JC, Ballman KV, Le-Petross HT, McCall LM, Mittendorf EA, Ahrendt GM, 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: Re- sults from ACOSOG Z1071 (Alliance) Annals of Surgery. 2016; 263: 802–807.

[24] Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Hep- pner BI, Weber KE, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol- ogy. 2018; 19: 40–50.

[25] O’Halloran N, Lowery A, Curran C, McLaughlin R, Malone C, Sweeney K, et al. A Review of the Impact of Neoadjuvant Chemotherapy on Breast Surgery Practice and Outcomes. Clini- cal Breast Cancer. 2019; 19: 377–382.

[26] Boileau J, Poirier B, Basik M, Holloway CMB, Gaboury L, Sideris L, et al. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. Journal of Clinical Oncology. 2015; 33: 258–264.

[27] Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncology. 2013; 14: 609–618.

[28] Classe J, Loaec C, Gimbergues P, Alran S, de Lara CT, Dupre PF, et al. Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for se- lected patients: the GANEA 2 study. Breast Cancer Research and Treatment. 2019; 173: 343–352.

[29] Kuemmel S, Heil J, Rueland A, Seiberling C, Harrach H, Schin- dowski D, et al. A Prospective, Multicenter Registry Study to Eval- uate the Clinical Feasibility of Targeted Axillary Dissection (TAD) in Node-Positive Breast Cancer Patients. Annals of Surgery. 2020. (in press)

[30] Banys-Paluchowski M, Gasparri ML, de Boniface J, Gentilini O, Stickeler E, Hartmann S, et al. The Axsana Study Group. 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 AXSANA Study. Cancers. 2021; 13: 1565.