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Major Reduction in Axillary Lymph Node Dissections After Neoadjuvant Systemic Therapy for Node-Positive Breast Cancer by combining PET/CT and the MARI Procedure

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Axillary lymph node dissection (ALND) is frequently performed for node-positive (cN+) breast cancer patients. Combining positron emission tomography/computed tomography (PET/CT) before-NST and the MARI (marking axillary lymph nodes with radioactive iodine seeds) procedure after neoadjuvant systemic therapy (NST) has the potential for avoiding unnecessary ALNDs. This report presents the results from implementation of this strategy.

Methods

All breast cancer patients treated with NST at the Netherlands Cancer Institute who underwent a PET/CT and the MARI procedure from July 2014 to July 2017 were included in the study. All the patients underwent tailored axillary treatment according to a protocol based on the combined results of PET/CT before NST and the MARI procedure after NST. With this protocol, patients showing one to three FDG-avid axillary lymph nodes (ALNs) on PET/CT (cN<4) and a tumor-negative MARI node receive no further axillary treatment. All cN (<4) patients with a tumor-positive MARI node receive locoregional radiotherapy, as well as patients with four or more FDG-avid ALNs [cN(4+)] and a tumor-negative MARI node after NST. An ALND is performed only for cN(4+) patients with a tumor-positive MARI node.

Results

The data of 159 patients who received a PET/CT before NST and a MARI procedure after NST were analyzed. Of these patients, 110 had one to three FDG-avid ALNs and 49 patients showed four or more FDG-avid ALNs on PET/CT before NST. For 130 patients (82%), ALND was omitted. Locoregional radiotherapy was administered to 91 patients (57%), and 39 patients (25%) received no further axillary treatment.

Conclusion

Combining pre-NST axillary staging with PET/CT and post-NST staging with the MARI procedure resulted in an 82% reduction of ALNDs for cN + breast cancer patients.

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References

  1. 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;260:608–14.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Dominici LS, Negron Gonzalez VM, Buzdar AU, et al. Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2-positive breast cancer. Cancer. 2010;116:2884–9.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Diego EJ, McAuliffe PF, Soran A, et al. Axillary staging after neoadjuvant chemotherapy for breast cancer: a pilot study combining sentinel lymph node biopsy with radioactive seed localization of pretreatment positive axillary lymph nodes. Ann Surg Oncol. 2016;23:1549–1553.

    Article  PubMed  Google Scholar 

  4. Hennessy BT, Hortobagyi GN, Rouzier R, et al. Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy. J Clin Oncol. 2005;23:9304–9311.

    Article  PubMed  Google Scholar 

  5. Rouzier R, Extra JM, Klijanienko J, et al. Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes. J Clin Oncol. 2002;20:1304–1310.

    Article  PubMed  Google Scholar 

  6. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.

    Article  PubMed  Google Scholar 

  7. Mougalian SS, Hernandez M, Lei X, et al. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol. 2016;2:508–16.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ashikaga T, Krag DN, Land SR, et al. Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection. J Surg Oncol. 2010;102:111–118.

    Article  PubMed  PubMed Central  Google Scholar 

  9. DiSipio T, Rye S, Newman B, et al. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol. 2013;14:500–515.

    Article  PubMed  Google Scholar 

  10. Koolen BB, Valdes Olmos RA, Elkhuizen PH, et al. Locoregional lymph node involvement on 18F-FDG PET/CT in breast cancer patients scheduled for neoadjuvant chemotherapy. Breast Cancer Res Treat. 2012;135:231–40.

    Article  PubMed  Google Scholar 

  11. Riegger C, Koeninger A, Hartung V, et al. Comparison of the diagnostic value of FDG-PET/CT and axillary ultrasound for the detection of lymph node metastases in breast cancer patients. Acta Radiol. 2012;53:1092–98.

    Article  PubMed  Google Scholar 

  12. Koolen BB, Valdes Olmos RA, Vogel WV, et al. Pre-chemotherapy 18F-FDG PET/CT upstages nodal stage in stage II–III breast cancer patients treated with neoadjuvant chemotherapy. Breast Cancer Res Treat. 2013;141:249–54.

    Article  CAS  PubMed  Google Scholar 

  13. Garg PK, Deo SV, Kumar R, et al. Staging PET-CT scanning provides superior detection of lymph nodes and distant metastases than traditional imaging in locally advanced breast cancer. World J Surg. 2016;40:2036–42.

    Article  PubMed  Google Scholar 

  14. Schipper RJ, Moossdorff M, Beets-Tan RG, et al. Noninvasive nodal restaging in clinically node positive breast cancer patients after neoadjuvant systemic therapy: a systematic review. Eur J Radiol. 2015;84:41–7.

    Article  CAS  PubMed  Google Scholar 

  15. Chung A, Giuliano A. Axillary staging in the neoadjuvant setting. Ann Surg Oncol. 2010;17:2401–10.

    Article  PubMed  Google Scholar 

  16. van la Parra RF, Kuerer HM. Selective elimination of breast cancer surgery in exceptional responders: historical perspective and current trials. Breast Cancer Res. 2016;18:28.

    Article  Google Scholar 

  17. 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;14:609–18.

    Article  PubMed  Google Scholar 

  18. 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;310:1455–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. van Nijnatten TJ, Schipper RJ, Lobbes MB, et al. The diagnostic performance of sentinel lymph node biopsy in pathologically confirmed node positive breast cancer patients after neoadjuvant systemic therapy: a systematic review and meta-analysis. Eur J Surg Oncol. 2015;41:1278–87.

    Article  PubMed  Google Scholar 

  20. Boughey JC, Ballman KV, Hunt KK, et al. Axillary ultrasound after neoadjuvant chemotherapy and its impact on sentinel lymph node surgery: results from the American College of Surgeons Oncology Group Z1071 Trial (Alliance). J Clin Oncol. 2015;33:3386–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. ME, Loo CE, Alderliesten T, et al. 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. 2010;97:1226–31.

    Article  CAS  PubMed  Google Scholar 

  22. Donker M, Straver ME, Wesseling J, et al. Marking axillary lymph nodes with radioactive iodine seeds for axillary staging after neoadjuvant systemic treatment in breast cancer patients: the MARI procedure. Ann Surg. 2015;261:378–82.

    Article  PubMed  Google Scholar 

  23. Koolen BB, Donker M, Straver ME, et al. Combined PET-CT and axillary lymph node marking with radioactive iodine seeds (MARI procedure) for tailored axillary treatment in node-positive breast cancer after neoadjuvant therapy. Br J Surg. 2017;104:1188–96.

    Article  CAS  PubMed  Google Scholar 

  24. Kimijima I, Yoshida K, Tamura R, et al. Effectiveness of multi-detector row computed tomography in detection of the presence and extent of ductal carcinoma in situ. Breast Cancer. 2013:20:26–33.

    Article  PubMed  Google Scholar 

  25. Alderliesten T, Loo CE, Pengel KE, et al. Radioactive seed localization of breast lesions: an adequate localization method without seed migration. Breast J. 2011;17:594–601.

    Article  PubMed  Google Scholar 

  26. Nielsen MH, Berg M, Pedersen AN, et al. Delineation of target volumes and organs at risk in adjuvant radiotherapy of early breast cancer: national guidelines and contouring atlas by the Danish Breast Cancer Cooperative Group. Acta Oncol. 2013;52:703–10.

    Article  PubMed  Google Scholar 

  27. Offersen BV, Boersma LJ, Kirkove C, et al. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early-stage breast cancer. Radiother Oncol. 2015;114:3–10.

    Article  PubMed  Google Scholar 

  28. Ergul N, Kadioglu H, Yildiz S, et al. Assessment of multifocality and axillary nodal involvement in early-stage breast cancer patients using 18F-FDG PET/CT compared to contrast-enhanced and diffusion-weighted magnetic resonance imaging and sentinel node biopsy. Acta Radiol. 2015;56:917–23.

    Article  PubMed  Google Scholar 

  29. Nursal GN, Nursal TZ, Aytac HO, et al. Is PET/CT necessary in the management of early breast cancer? Clin Nucl Med. 2016;41:362–5.

    Article  PubMed  Google Scholar 

  30. Huang EH, Strom EA, Perkins GH, et al. Comparison of risk of local-regional recurrence after mastectomy or breast conservation therapy for patients treated with neoadjuvant chemotherapy and radiation stratified according to a prognostic index score. Int J Radiat Oncol Biol Phys. 2006;66:352–7.

    Article  PubMed  Google Scholar 

  31. Hong S, Li J, Wang S. 18FDG PET-CT for diagnosis of distant metastases in breast cancer patients: a meta-analysis. Surg Oncol. 2013;22:139–43.

    Article  PubMed  Google Scholar 

  32. 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;34:1072–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 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;263:802–7.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg. 2010;252:426–32.

    PubMed  PubMed Central  Google Scholar 

  35. Giuliano AE, Ballman K, McCall L, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial. Ann Surg. 2016;264:413–20.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26:778–85.

    Article  PubMed  Google Scholar 

  37. Mamounas EP, Bandos H, White JR, et al. NRG Oncology/NSABP B-51/RTOG 1304: phase III trial to determine if chest wall and regional nodal radiotherapy (CWRNRT) post mastectomy (Mx) or the addition of RNRT to breast RT post breast-conserving surgery (BCS) reduces invasive breast cancer recurrence-free interval (IBCRFI) in patients (pts) with positive axillary (PAx) nodes who are ypN0 after neoadjuvant chemotherapy (NC). J Clin Oncol. 2017;35:TPS589–TPS589.

  38. 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;15:1303–10.

    Article  PubMed  PubMed Central  Google Scholar 

  39. King TA, Morrow M. Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy. Nat Rev Clin Oncol. 2015;12:335–43.

    Article  PubMed  Google Scholar 

  40. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366:2087–106.

    Article  CAS  PubMed  Google Scholar 

  41. Braunstein LZ, Galland-Girodet S, Goldberg S, et al. Long-term outcomes among breast cancer patients with extensive regional lymph node involvement: implications for locoregional management. Breast Cancer Res Treat. 2015;154:633–9.

    Article  PubMed  Google Scholar 

  42. Koolen BB, Donker M, Straver ME, et al. Combined PET-CT and axillary lymph node marking with radioactive iodine seeds (MARI procedure) for tailored axillary treatment in node-positive breast cancer after neoadjuvant therapy. Br J Surg. 2017 104(9):1188–96.

    Article  CAS  PubMed  Google Scholar 

  43. Koolen BB, Vrancken Peeters MJ, Aukema TS, et al. 18F-FDG PET/CT as a staging procedure in primary stage II and III breast cancer: comparison with conventional imaging techniques. Breast Cancer Res Treat. 2012;131:117–26.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgical Oncology, the Netherlands Cancer Institute–Antoni van Leeuwenhoek, Amsterdam, The Netherlands

    M. E. M. van der Noordaa MD, F. H. van Duijnhoven MD, PhD & M. T. F. D. Vrancken Peeters MD, PhD

  2. Department of Surgery, Haaglanden Medical Centre, The Hague, The Netherlands

    M. E. Straver MD, PhD

  3. Department of Pathology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek, Amsterdam, The Netherlands

    E. J. Groen MD

  4. Department of Nuclear Medicine, The Netherlands Cancer Institute–Antoni van Leeuwenhoek, Amsterdam, The Netherlands

    M. Stokkel MD, PhD

  5. Department of Radiology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek, Amsterdam, The Netherlands

    C. E. Loo MD, PhD

  6. Department of Radiation Oncology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek, Amsterdam, The Netherlands

    P. H. M. Elkhuizen MD, PhD & N. S. Russell MD, PhD

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  1. M. E. M. van der Noordaa MD
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  2. F. H. van Duijnhoven MD, PhD
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  3. M. E. Straver MD, PhD
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  6. C. E. Loo MD, PhD
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Correspondence to M. T. F. D. Vrancken Peeters MD, PhD.

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van der Noordaa, M.E.M., van Duijnhoven, F.H., Straver, M.E. et al. Major Reduction in Axillary Lymph Node Dissections After Neoadjuvant Systemic Therapy for Node-Positive Breast Cancer by combining PET/CT and the MARI Procedure. Ann Surg Oncol 25, 1512–1520 (2018). https://doi.org/10.1245/s10434-018-6404-y

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  • DOI: https://doi.org/10.1245/s10434-018-6404-y

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