Skip to main content
SpringerLink
Log in

Management of the Axilla after Neoadjuvant Systemic Therapy

  • Breast Cancer (WJ Gradishar, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

As the use of neoadjuvant systemic therapy (NAST) increases, the optimal management of the axilla has become increasingly complex. Consensus among professional organizations is that those patients with clinically negative axillary nodes who are being considered for NAST should undergo a sentinel lymph node (SLN) biopsy following NAST. If a positive SLN is subsequently identified, an axillary lymph node dissection (ALND) is the current standard of care. For patients with clinically node-positive disease, SLN biopsy is a reasonable option for those with a good response to NAST. Patients should undergo SLN mapping with a dual dye technique. Additionally, at least 2 lymph nodes should be removed, including the previously biopsied and marked lymph node with cancer. In this setting, the identification and false negative rates are acceptable. Patients found to have a negative SLN at this time may be spared the morbidity associated with ALND. Patients found to have persistently positive lymph nodes following NAST, either clinically or pathologically, should undergo a complete ALND.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16(8):2672–85.

    Article  CAS  Google Scholar 

  2. Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26(5):778–85.

    Article  Google Scholar 

  3. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018;19(1):27–39.

  4. Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;30:96–102.

    Article  Google Scholar 

  5. Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15(7):2483–93.

    Article  CAS  Google Scholar 

  6. Broglio KR, Quintana M, Foster M, Olinger M, McGlothlin A, Berry SM, et al. Association of pathologic complete response to neoadjuvant therapy in HER2-positive breast cancer with long-term outcomes: a meta-analysis. JAMA Oncol. 2016;2(6):751–60.

    Article  Google Scholar 

  7. Chollet P, Amat S, Cure H, de Latour M, le Bouedec G, Mouret-Reynier MA, et al. Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer. Br J Cancer. 2002;86(7):1041–6.

    Article  CAS  Google Scholar 

  8. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72.

    Article  Google Scholar 

  9. Boughey JC, Ballman KV, McCall LM, Mittendorf EA, Symmans WF, Julian TB, et al. Tumor biology and response to chemotherapy impact breast cancer-specific survival in node-positive breast cancer patients treated with neoadjuvant chemotherapy: long-term follow-up from ACOSOG Z1071 (Alliance). Ann Surg. 2017;266(4):667–76.

    Article  Google Scholar 

  10. Murphy BL, Day CN, Hoskin TL, Habermann EB, Boughey JC. Neoadjuvant chemotherapy use in breast cancer is greatest in excellent responders: triple-negative and HER2+ subtypes. Ann Surg Oncol. 2018;25(8):2241–8.

    Article  Google Scholar 

  11. Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989;63(1):181–7.

    Article  CAS  Google Scholar 

  12. Fisher B, Bauer M, Wickerham DL, Redmond CK, Fisher ER, Cruz AB, et al. Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer. 1983;52(9):1551–7.

    Article  CAS  Google Scholar 

  13. Soerjomataram I, Louwman MW, Ribot JG, Roukema JA, Coebergh JW. An overview of prognostic factors for long-term survivors of breast cancer. Breast Cancer Res Treat. 2008;107(3):309–30.

    Article  CAS  Google Scholar 

  14. Nemoto T, Vana J, Bedwani RN, Baker HW, McGregor FH, Murphy GP. Management and survival of female breast cancer: results of a national survey by the American College of Surgeons. Cancer. 1980;45(12):2917–24.

    Article  CAS  Google Scholar 

  15. NCCN Clinical Practice Guidelines in Oncology for Breast Cancer. National Comprehensive Cancer Network. Published 2019. Accessed May 20, 2019. This article reports the current evidence-based practice guidelines in breast cancer as determined by the National Comprehensive Cancer Network.

  16. Silverstein MJ, Recht A, Lagios MD, Bleiweiss IJ, Blumencranz PW, Gizienski T, et al. Special report: consensus conference III. Image-detected breast cancer: state-of-the-art diagnosis and treatment. J Am Coll Surg. 2009;209(4):504–20.

    Article  Google Scholar 

  17. Dahabreh IJ, Wieland LS, Adam GP, Halladay C, Lau J, Trikalinos TA. AHRQ comparative effectiveness reviews. In: Core Needle and Open Surgical Biopsy for Diagnosis of Breast Lesions: An Update to the 2009 Report. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014.

  18. Wang M, He X, Chang Y, Sun G, Thabane L. A sensitivity and specificity comparison of fine needle aspiration cytology and core needle biopsy in evaluation of suspicious breast lesions: a systematic review and meta-analysis. Breast. 2017;31:157–66.

    Article  Google Scholar 

  19. 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.

  20. Hunt KK, Yi M, Mittendorf EA, Guerrero C, Babiera GV, Bedrosian I, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy is accurate and reduces the need for axillary dissection in breast cancer patients. Ann Surg. 2009;250(4):558–66.

    PubMed  Google Scholar 

  21. Zhang L, Liu C, Wang W, Xu X, Chen B. Is optimal timing of sentinel lymph node biopsy before neoadjuvant chemotherapy in patients with breast cancer? A literature review. Surg Oncol. 2012;21(4):252–6.

    Article  Google Scholar 

  22. Consensus Guideline on the Management of the Axilla in Patients With Invasive/In-Situ Breast Cancer. https://www.breastsurgeons.org/docs/statements/Consensus-Guideline-on-the-Management-of-the-Axilla.pdf?v2. Published 2019. Accessed December 20, 2019.

  23. Grube BJ, Christy CJ, Black D, et al. Breast sentinel lymph node dissection before preoperative chemotherapy. Arch Surg. 2008;143(7):692–9 discussion 699-700.

    Article  Google Scholar 

  24. Schrenk P, Tausch C, Wolfl S, Bogner S, Fridrik M, Wayand W. Sentinel node mapping performed before preoperative chemotherapy may avoid axillary dissection in breast cancer patients with negative or micrometastatic sentinel nodes. Am J Surg. 2008;196(2):176–83.

    Article  Google Scholar 

  25. Papa MZ, Zippel D, Kaufman B, Shimon-Paluch S, Yosepovich A, Oberman B, et al. Timing of sentinel lymph node biopsy in patients receiving neoadjuvant chemotherapy for breast cancer. J Surg Oncol. 2008;98(6):403–6.

    Article  Google Scholar 

  26. Xing Y, Foy M, Cox DD, Kuerer HM, Hunt KK, Cormier JN. Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer. Br J Surg. 2006;93(5):539–46.

    Article  CAS  Google Scholar 

  27. Classe JM, Bordes V, Campion L, Mignotte H, Dravet F, Leveque J, et al. Sentinel lymph node biopsy after neoadjuvant chemotherapy for advanced breast cancer: results of ganglion sentinelle et chimiotherapie neoadjuvante, a French prospective multicentric study. J Clin Oncol. 2009;27(5):726–32.

    Article  Google Scholar 

  28. Pecha V, Kolarik D, Kozevnikova R, Hovorkova K, Hrabetova P, Halaska M, et al. Sentinel lymph node biopsy in breast cancer patients treated with neoadjuvant chemotherapy. Cancer. 2011;117(20):4606–16.

    Article  Google Scholar 

  29. • Geng C, Chen X, Pan X, Li J. The feasibility and accuracy of sentinel lymph node biopsy in initially clinically node-negative breast cancer after neoadjuvant chemotherapy: a systematic review and meta-analysis. PLoS One. 2016;11(9):e0162605 This article is a meta-analysis of 16 studies that examined the outcome of SLN biopsy in clinically node negative patients who had undergone preoperative chemotherapy.

    Article  Google Scholar 

  30. Jeruss JS, Newman LA, Ayers GD, Cristofanilli M, Broglio KR, Meric-Bernstam F, et al. Factors predicting additional disease in the axilla in patients with positive sentinel lymph nodes after neoadjuvant chemotherapy. Cancer. 2008;112(12):2646–54.

    Article  Google Scholar 

  31. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. Jama. 2011;305(6):569–75.

    Article  CAS  Google Scholar 

  32. Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde C, Mansel RE, 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(12):1303–10.

    Article  Google Scholar 

  33. Galimberti V, Cole BF, Viale G, Veronesi P, Vicini E, Intra M, et al. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial. Lancet Oncol. 2018;19(10):1385–93.

    Article  Google Scholar 

  34. Lucci A, McCall LM, Beitsch PD, Whitworth PW, Reintgen DS, Blumencranz PW, et al. Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group rial Z0011. J Clin Oncol. 2007;25(24):3657–63.

    Article  Google Scholar 

  35. Warmuth MA, Bowen G, Prosnitz LR, Chu L, Broadwater G, Peterson B, et al. Complications of axillary lymph node dissection for carcinoma of the breast: a report based on a patient survey. Cancer. 1998;83(7):1362–8.

    Article  CAS  Google Scholar 

  36. Shaw JH, Rumball EM. Complications and local recurrence following lymphadenectomy. Br J Surg. 1990;77(7):760–4.

    Article  CAS  Google Scholar 

  37. Boughey JC, McCall LM, Ballman KV, et al. Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (Alliance) prospective multicenter clinical trial. Ann Surg. 2014;260(4):608–14 discussion 614-606.

    Article  Google Scholar 

  38. •• Kuehn T, Bauerfeind I, Fehm T, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14(7):609–18 This article reported on a prospective, multicenter study examining the appropriate timing of SLN biopsy in patients undergoing NAST. Arm C specifically examines 592 patients with clinically node positive disease that converted to clinically node negative following NAST. The identification rate was 80.1% and FNR was 14.2% with improvement of the FNR to 9.6% when ≥3 LN were removed and 8.6% when a dual dye technique was used.

    Article  Google Scholar 

  39. •• Boughey JC, Suman VJ, Mittendorf EA, 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(14):1455–61 This article reported on a prospective, multicenter study examining SLN biopsy in 637 patients undergoing NAST. All women underwent SLN biopsy followed by ALND. The identification rate was 92.7% and FNR was 12.6% with improvement of the FNR to 9.1% when ≥3 LN were removed and 10.8% when a dual dye technique was used.

    Article  CAS  Google Scholar 

  40. •• 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(3):258–64 This article reported on a prospective, multicenter study examining SLN biopsy in 135 patients with node positive breast cancer undergoing NAST. All women underwent SLN biopsy followed by ALND. IHC diase and ITC’s were considered to be positive. The identification rate was 87.6% and FNR was 8.4% with improvement of the FNR to 4.9% when ≥2 LN were removed and 5.2% when a dual dye technique was used.

    Article  Google Scholar 

  41. • 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(4):802–7 This article is a subanalysis of the ACOSOG Z1071 examining 203 patients with node positive disease who had their biopsied node marked with a clip prior to undergoing NAST. All patients underwent a SLN biopsy followed by ALND. The FNR was reported to be 6.8% when the clipped node was within the post-NAST SLN specimen compared to 24.1% when the clipped node was within the ALND specimen.

    Article  Google Scholar 

  42. •• Caudle AS, Yang WT, Krishnamurthy S, et al. 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;34(10):1072–8 This article was a prospective study of 191 patients with node positive disease who had their biopsied node marked with a clip prior to undergoing NAST. Patients underwent a SLN biopsy +/− targeted axillary dissection with iodine-125 seeds to localize and remove the clipped node followed by an ALND. A SLN biopsy + TAD resulted in a FNR of 1.4%.

    Article  CAS  Google Scholar 

  43. Choy N, Lipson J, Porter C, et al. Initial results with preoperative tattooing of biopsied axillary lymph nodes and correlation to sentinel lymph nodes in breast cancer patients. Ann Surg Oncol. 2015;22(2):377–82.

    Article  Google Scholar 

  44. Dashevsky BZ, Altman A, Abe H, Jaskowiak N, Bao J, Schacht DV, et al. Lymph node wire localization post-chemotherapy: towards improving the false negative sentinel lymph node biopsy rate in breast cancer patients. Clin Imaging. 2018;48:69–73.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Wisconsin Surgical Outcomes Research Program, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Trista J. Stankowski-Drengler MD, MS & Heather B. Neuman MD, MS

  2. University of Wisconsin Carbone Cancer Center, Madison, WI, USA

    Heather B. Neuman MD, MS

Authors
  1. Trista J. Stankowski-Drengler MD, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heather B. Neuman MD, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heather B. Neuman MD, MS.

Ethics declarations

Conflict of Interest

Trista J. Stankowski-Drengler and Heather B. Neuman declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Breast Cancer

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stankowski-Drengler, T.J., Neuman, H.B. Management of the Axilla after Neoadjuvant Systemic Therapy. Curr. Treat. Options in Oncol. 21, 54 (2020). https://doi.org/10.1007/s11864-020-00755-7

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11864-020-00755-7

Keywords

Search

Navigation