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Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for selected patients: the GANEA 2 study

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Abstract

Purpose

GANEA2 study was designed to assess accuracy and safety of sentinel lymph node (SLN) after neo-adjuvant chemotherapy (NAC) in breast cancer patients.

Methods

Early breast cancer patients treated with NAC were included. Before NAC, patients with cytologically proven node involvement were allocated into the pN1 group, other patient were allocated into the cN0 group. After NAC, pN1 group patients underwent SLN and axillary lymph node dissection (ALND); cN0 group patients underwent SLN and ALND only in case of mapping failure or SLN involvement. The main endpoint was SLN false negative rate (FNR). Secondary endpoints were predictive factors for remaining positive ALND and survival of patients treated with SLN alone.

Results

From 2010 to 2014, 957 patients were included. Among the 419 patients from the cN0 group treated with SLN alone, one axillary relapse occurred during the follow-up. Among pN1 group patients, with successful mapping, 103 had a negative SLN. The FNR was 11.9% (95% CI 7.3–17.9%). Multivariate analysis showed that residual breast tumor size after NAC ≥ 5 mm and lympho-vascular invasion remained independent predictors for involved ALND. For patients with initially involved node, with negative SLN after NAC, no lympho-vascular invasion and a remaining breast tumor size 5 mm, the risk of a positive ALND is 3.7% regardless the number of SLN removed.

Conclusion

In patients with no initial node involvement, negative SLN after NAC allows to safely avoid an ALND. Residual breast tumor and lympho-vascular invasion after NAC allow identifying patients with initially involved node with a low risk of ALND involvement.

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References

  1. Krag D, Weaver D, Ashikaga T et al (1998) The sentinel node in breast cancer: a multicenter validation study. N Engl J Med 339:941–946. https://doi.org/10.1056/NEJM199810013391401

    Article  PubMed  CAS  Google Scholar 

  2. Mansel RE, Fallowfield L, Kissin M et al (2006) Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst 98:599–609. https://doi.org/10.1093/jnci/djj158

    Article  PubMed  Google Scholar 

  3. Bear HD, Anderson S, Brown A et al (2003) The effect on tumour response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 21:4165–4174. https://doi.org/10.1200/JCO.2003.12.005

    Article  PubMed  CAS  Google Scholar 

  4. Shen J, Gilcrease MZ, Babiera GV et al (2007) Feasibility and accuracy of sentinel lymph node biopsy after preoperative chemotherapy in breast cancer patients with documented axillary metastases. Cancer 109:1255–1263. https://doi.org/10.1002/cncr.22540

    Article  PubMed  Google Scholar 

  5. Hennessy BT, Hortobagyi GN, Rouzier R et al (2005) Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy. J Clin Oncol 23:9304–9311. https://doi.org/10.1200/JCO.2005.02.5023

    Article  PubMed  Google Scholar 

  6. Boughey JC, Suman VJ, Mittendorf EA et al (2013) Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA 310:1455–1461. https://doi.org/10.1001/jama.2013.278932

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Gianni L, Pienkowski T, Im YH et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13(1):25–32. https://doi.org/10.1016/S1470-2045(11)70336-9

    Article  PubMed  CAS  Google Scholar 

  8. Fisher ER, Wang J, Bryant J et al (2002) Pathobiology of preoperative chemotherapy: findings from the National Surgical Adjuvant Breast and Bowel (NSABP) protocol B-18. Cancer 95:681–695. https://doi.org/10.1002/cncr.10741

    Article  PubMed  Google Scholar 

  9. Xing Y, Foy M, Cox DD et al (2006) Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer. Br J Surg 93:539–546. https://doi.org/10.1002/bjs.5209

    Article  PubMed  CAS  Google Scholar 

  10. Mamounas EP, Brown A, Anderson S et al (2005) Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 23:2694–2702. https://doi.org/10.1200/JCO.2005.05.188

    Article  PubMed  Google Scholar 

  11. El Hage Chehade H, Headon H, Kasem A, Mokbel K (2016) Refining the performance of sentinel lymph node biopsy post-neoadjuvant chemotherapy in patients with pathologically proven pre-treatment node-positive breast cancer: an update for clinical practice. Anticancer Res 36:1461–1471

    PubMed  Google Scholar 

  12. Valachis A, Mamounas EP, Mittendorf EA et al (2018) Risk factors for locoregional disease recurrence after breast-conserving therapy in patients with breast cancer treated with neoadjuvant chemotherapy: an international collaboration and individual patient meta-analysis: recurrence after neoadjuvant chemotherapy. Cancer. https://doi.org/10.1002/cncr.31518

    Article  PubMed  Google Scholar 

  13. Lyman GH, Temin S, Edge SB et al (2014) Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 32:1365–1383. https://doi.org/10.1200/JCO.2013.54.1177

    Article  PubMed  Google Scholar 

  14. Lyman GH, Somerfield MR, Bosserman LD et al (2017) Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology Clinical practice guideline update. J Clin Oncol 35:561–564. https://doi.org/10.1200/JCO.2016.71.0947

    Article  PubMed  Google Scholar 

  15. Curigliano G, Burstein HJ, Winer EP et al (2018) De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. https://doi.org/10.1093/annonc/mdx806

    Article  PubMed  PubMed Central  Google Scholar 

  16. Krag DN, Anderson SJ, Julian TB et al (2007) Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. Lancet Oncol 8:881–888. https://doi.org/10.1016/S1470-2045(07)70278-4

    Article  PubMed  CAS  Google Scholar 

  17. McCready DR, Yong WS, Ng AKT et al (2004) Influence of the new AJCC breast cancer staging system on sentinel lymph node positivity and false-negative rates. J Natl Cancer Inst 96:873–875

    Article  PubMed  Google Scholar 

  18. Classe J-M, Bordes V, Campion L et al (2009) 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 27:726–732. https://doi.org/10.1200/JCO.2008.18.3228

    Article  PubMed  Google Scholar 

  19. Nogi H, Uchida K, Mimoto R et al (2017) Long-term follow-up of node-negative breast cancer patients evaluated via sentinel node biopsy after neoadjuvant chemotherapy. Clin Breast Cancer 17:644–649. https://doi.org/10.1016/j.clbc.2017.05.002

    Article  PubMed  Google Scholar 

  20. 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 Oncol 14:609–618. https://doi.org/10.1016/S1470-2045(13)70166-9

    Article  PubMed  Google Scholar 

  21. Boileau J-F, 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. https://doi.org/10.1200/JCO.2014.55.7827

    Article  PubMed  Google Scholar 

  22. Fu J-F, Chen H-L, Yang J et al (2014) Feasibility and accuracy of sentinel lymph node biopsy in clinically node-positive breast cancer after neoadjuvant chemotherapy: a meta-analysis. PLoS ONE 9:e105316. https://doi.org/10.1371/journal.pone.0105316

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Tadros AB, Yang WT, Krishnamurthy S et al (2017) Identification of patients with documented pathologic complete response in the breast after neoadjuvant chemotherapy for omission of axillary surgery. JAMA Surg 152:665. https://doi.org/10.1001/jamasurg.2017.0562

    Article  PubMed  PubMed Central  Google Scholar 

  24. Schipper R-J, Moossdorff M, Nelemans PJ et al (2014) A model to predict pathologic complete response of axillary lymph nodes to neoadjuvant chemo(immuno)therapy in patients with clinically node-positive breast cancer. Clin Breast Cancer 14:315–322. https://doi.org/10.1016/j.clbc.2013.12.015

    Article  PubMed  CAS  Google Scholar 

  25. Vila J, Mittendorf EA, Farante G et al (2016) Nomograms for predicting axillary response to neoadjuvant chemotherapy in clinically node-positive patients with breast cancer. Ann Surg Oncol 23:3501–3509. https://doi.org/10.1245/s10434-016-5277-1

    Article  PubMed  Google Scholar 

  26. Jeruss JS, Newman LA, Ayers GD et al (2008) Factors predicting additional disease in the axilla in patients with positive sentinel lymph nodes after neoadjuvant chemotherapy. Cancer 112:2646–2654. https://doi.org/10.1002/cncr.23481

    Article  PubMed  PubMed Central  Google Scholar 

  27. 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. https://doi.org/10.1200/JCO.2015.64.0094

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. 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 261:378–382. https://doi.org/10.1097/SLA.0000000000000558

    Article  PubMed  Google Scholar 

  29. 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 22:377–382. https://doi.org/10.1245/s10434-014-4034-6

    Article  PubMed  Google Scholar 

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Acknowledgements

We received financial support from the French National Institute of Oncology (National Program for Hospital Clinical Research 2009, INCA) (Grant No. NCT01221688). We thank Valerie Pacteau (Clinical project manager, Institut de Cancerologie de l’Ouest Gauducheau), Camille Berneur (data manager, Institut de Cancerologie de l’Ouest Gauducheau), Wilfried Blot and Emilie Debeaupuis (Clinical research associates, Institut de Cancerologie de l’Ouest Gauducheau) for study support and Adrian Chess and Bryce Van Denderen (Ecomod, UK) for English revision.

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Correspondence to Jean-Marc Classe.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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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 173, 343–352 (2019). https://doi.org/10.1007/s10549-018-5004-7

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  • DOI: https://doi.org/10.1007/s10549-018-5004-7

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