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International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases

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Abstract

Recently, many centers have omitted routine axillary lymph node dissection (ALND) after metastatic sentinel node biopsy in breast cancer due to a growing body of literature. However, existing guidelines of adjuvant treatment planning are strongly based on axillary nodal stage. In this study, we aim to develop a novel international multicenter predictive tool to estimate a patient-specific risk of having four or more tumor-positive axillary lymph nodes (ALN) in patients with macrometastatic sentinel node(s) (SN). A series of 675 patients with macrometastatic SN and completion ALND from five European centers were analyzed by logistic regression analysis. A multivariate predictive model was created and validated internally by 367 additional patients and then externally by 760 additional patients from eight different centers. All statistical tests were two-sided. Prevalence of four or more tumor-positive ALN in each center’s series (P = 0.010), number of metastatic SNs (P < 0.0001), number of negative SNs (P = 0.003), histological size of the primary tumor (P = 0.020), and extra-capsular extension of SN metastasis (P < 0.0001) were included in the predictive model. The model’s area under the receiver operating characteristics curve was 0.766 in the internal validation and 0.774 in external validation. Our novel international multicenter-based predictive tool reliably estimates the risk of four or more axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our tool performs well in internal and external validation, but needs to be further validated in each center before application to clinical use.

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References

  1. Truong PT, Vinh-Hung V, Cserni G, Woodward WA, Tai P, Vlastos G, Group MotINRW (2008) The number of positive nodes and the ratio of positive to excised nodes are significant predictors of survival in women with micrometastatic node-positive breast cancer. Eur J Cancer 44(12):1670–1677

    Article  PubMed  Google Scholar 

  2. Vinh-Hung V, Verkooijen HM, Fioretta G, Neyroud-Caspar I, Rapiti E, Vlastos G, Deglise C, Usel M, Lutz JM, Bouchardy C (2009) Lymph node ratio as an alternative to pN staging in node-positive breast cancer. J Clin Oncol 27(7):1062–1068

    Article  PubMed  Google Scholar 

  3. Kim T, Giuliano AE, Lyman GH (2006) Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis. Cancer 106(1):4–16

    Article  PubMed  Google Scholar 

  4. Gärtner R, Jensen MB, Nielsen J, Ewertz M, Kroman N, Kehlet H (2009) Prevalence of and factors associated with persistent pain following breast cancer surgery. JAMA 302(18):1985–1992

    Article  PubMed  Google Scholar 

  5. Giuliano AE, McCall L, Beitsch P, Whitworth PW, Blumencranz P, Leitch AM, Saha S, Hunt KK, Morrow M, Ballman K (2010) 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 252(3):426–432 discussion 432–433

    PubMed  Google Scholar 

  6. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, McCall LM, Morrow M (2011) Axillary dissection vs. no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 305(6):569–575

    Article  PubMed  CAS  Google Scholar 

  7. Wasif N, Ye X, Giuliano AE (2009) Survey of ASCO members on management of sentinel node micrometastases in breast cancer: variation in treatment recommendations according to specialty. Ann Surg Oncol 16(9):2442–2449

    Article  PubMed  Google Scholar 

  8. Bilimoria K, Bentrem D, Hansen N, Bethke K, Rademaker A, Ko C, Winchester D, Winchester D (2009) Comparison of sentinel lymph node biopsy alone and completion axillary lymph node dissection for node-positive breast cancer. J Clin Oncol 27(18):2946–2953

    Article  PubMed  Google Scholar 

  9. Pepels MJ, Vestjens JH, de Boer M, Smidt M, van Diest PJ, Borm GF, Tjan-Heijnen VC (2011) Safety of avoiding routine use of axillary dissection in early stage breast cancer: a systematic review. Breast Cancer Res Treat 125(2):301–313

    Article  PubMed  Google Scholar 

  10. Recht A, Edge SB, Solin LJ, Robinson DS, Estabrook A, Fine RE, Fleming GF, Formenti S, Hudis C, Kirshner JJ et al (2001) Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 19(5):1539–1569

    PubMed  CAS  Google Scholar 

  11. Aebi S, Davidson T, Gruber G, Cardoso F, Group EGW (2011) Primary breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 22(Suppl 6):vi12–vi24

    Article  PubMed  Google Scholar 

  12. Chagpar AB, Scoggins CR, Martin RC, Cook EF, McCurry T, Mizuguchi N, Paris KJ, Carlson DJ, Laidley AL, El-Eid SE et al (2007) Predicting patients at low probability of requiring postmastectomy radiation therapy. Ann Surg Oncol 14(2):670–677

    Article  PubMed  Google Scholar 

  13. Rivers AK, Griffith KA, Hunt KK, Degnim AC, Sabel MS, Diehl KM, Cimmino VM, Chang AE, Lucas PC, Newman LA (2006) Clinicopathologic features associated with having four or more metastatic axillary nodes in breast cancer patients with a positive sentinel lymph node. Ann Surg Oncol 13(1):36–44

    Article  PubMed  Google Scholar 

  14. Katz A, Smith BL, Golshan M, Niemierko A, Kobayashi W, Raad RA, Kelada A, Rizk L, Wong JS, Bellon JR et al (2008) Nomogram for the prediction of having four or more involved nodes for sentinel lymph node-positive breast cancer. J Clin Oncol 26(13):2093–2098

    Article  PubMed  Google Scholar 

  15. Leidenius M, Vaalavirta L, Heikkilä P, von Smitten K, Salmenkivi K (2008) The prevalence of and risk factors for four or more metastatic axillary lymph nodes in breast cancer patients undergoing sentinel node biopsy. J Surg Oncol 98(1):21–26

    Article  PubMed  CAS  Google Scholar 

  16. Cserni G, Boross G, Maráz R, Leidenius MH, Meretoja TJ, Heikkila PS, Regitnig P, Luschin-Ebengreuth G, Zgajnar J, Perhavec A et al (2012) Multicentre validation of different predictive tools of non-sentinel lymph node involvement in breast cancer. Surg Oncol 21(2):59–65

    Article  PubMed  CAS  Google Scholar 

  17. Cserni G, Bori R, Maráz R, Leidenius MH, Meretoja TJ, Heikkila PS, Regitnig P, Luschin-Ebengreuth G, Zgajnar J, Perhavec A et al (2012) Multi-institutional comparison of non-sentinel lymph node predictive tools in breast cancer patients with high predicted risk of further axillary metastasis. Pathol Oncol Res. doi:10.1007/s12253-012-9553-5

    Google Scholar 

  18. Sobin LH, Wittekind Ch (eds) (2002) TNM classification of malignant tumours. Wiley-Liss, New York

    Google Scholar 

  19. Van Zee KJ, Manasseh DM, Bevilacqua JL, Boolbol SK, Fey JV, Tan LK, Borgen PI, Cody HS, Kattan MW (2003) A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy. Ann Surg Oncol 10(10):1140–1151

    Article  PubMed  Google Scholar 

  20. Hwang RF, Krishnamurthy S, Hunt KK, Mirza N, Ames FC, Feig B, Kuerer HM, Singletary SE, Babiera G, Meric F et al (2003) Clinicopathologic factors predicting involvement of nonsentinel axillary nodes in women with breast cancer. Ann Surg Oncol 10(3):248–254

    Article  PubMed  Google Scholar 

  21. Farshid G, Pradhan M, Kollias J, Gill PG (2004) A decision aid for predicting non-sentinel node involvement in women with breast cancer and at least one positive sentinel node. Breast 13(6):494–501

    Article  PubMed  Google Scholar 

  22. Saidi RF, Dudrick PS, Remine SG, Mittal VK (2004) Nonsentinel lymph node status after positive sentinel lymph node biopsy in early breast cancer. Am Surg 70(2):101–105 discussion 105

    PubMed  Google Scholar 

  23. Barranger E, Coutant C, Flahault A, Delpech Y, Darai E, Uzan S (2005) An axilla scoring system to predict non-sentinel lymph node status in breast cancer patients with sentinel lymph node involvement. Breast Cancer Res Treat 91(2):113–119

    Article  PubMed  Google Scholar 

  24. Degnim AC, Reynolds C, Pantvaidya G, Zakaria S, Hoskin T, Barnes S, Roberts MV, Lucas PC, Oh K, Koker M et al (2005) Nonsentinel node metastasis in breast cancer patients: assessment of an existing and a new predictive nomogram. Am J Surg 190(4):543–550

    Article  PubMed  Google Scholar 

  25. Chagpar AB, Scoggins CR, Martin RC, Carlson DJ, Laidley AL, El-Eid SE, McGlothin TQ, McMasters KM, Study UoLBSLN (2006) Prediction of sentinel lymph node-only disease in women with invasive breast cancer. Am J Surg 192(6):882–887

    Article  PubMed  Google Scholar 

  26. Pal A, Provenzano E, Duffy SW, Pinder SE, Purushotham AD (2008) A model for predicting non-sentinel lymph node metastatic disease when the sentinel lymph node is positive. Br J Surg 95(3):302–309

    Article  PubMed  CAS  Google Scholar 

  27. Houvenaeghel G, Nos C, Giard S, Mignotte H, Esterni B, Jacquemier J, Buttarelli M, Classe JM, Cohen M, Rouanet P et al (2009) A nomogram predictive of non-sentinel lymph node involvement in breast cancer patients with a sentinel lymph node micrometastasis. Eur J Surg Oncol 35(7):690–695

    Article  PubMed  CAS  Google Scholar 

  28. Kohrt HE, Olshen RA, Bermas HR, Goodson WH, Wood DJ, Henry S, Rouse RV, Bailey L, Philben VJ, Dirbas FM et al (2008) New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients. BMC Cancer 8:66

    Article  PubMed  Google Scholar 

  29. Cho J, Han W, Lee JW, Ko E, Kang SY, Jung SY, Kim EK, Moon WK, Cho N, Park IA et al (2008) A scoring system to predict nonsentinel lymph node status in breast cancer patients with metastatic sentinel lymph nodes: a comparison with other scoring systems. Ann Surg Oncol 15(8):2278–2286

    Article  PubMed  Google Scholar 

  30. Gur AS, Unal B, Ozbek U, Ozmen V, Aydogan F, Gokgoz S, Gulluoglu BM, Aksaz E, Ozbas S, Baskan S et al (2010) Validation of breast cancer nomograms for predicting the non-sentinel lymph node metastases after a positive sentinel lymph node biopsy in a multi-center study. Eur J Surg Oncol 36(1):30–35

    Article  PubMed  CAS  Google Scholar 

  31. Perhavec A, Perme MP, Hocevar M, Besić N, Zgajnar J (2010) Ljubljana nomograms for predicting the likelihood of non-sentinel lymph node metastases in breast cancer patients with a positive sentinel lymph node. Breast Cancer Res Treat 119(2):357–366

    Article  PubMed  Google Scholar 

  32. Coufal O, Pavlík T, Fabian P, Bori R, Boross G, Sejben I, Maráz R, Koca J, Krejcí E, Horáková I et al (2009) Predicting non-sentinel lymph node status after positive sentinel biopsy in breast cancer: what model performs the best in a Czech population? Pathol Oncol Res 15(4):733–740

    Article  PubMed  Google Scholar 

  33. Meretoja TJ, Strien L, Heikkilä PS, Leidenius MH (2012) A simple nomogram to evaluate the risk of nonsentinel node metastases in breast cancer patients with minimal sentinel node involvement. Ann Surg Oncol 19(2):567–576

    Article  PubMed  CAS  Google Scholar 

  34. Meretoja TJ, Leidenius MHK, Heikkilä PS et al (2012) International multicenter tool to predict the risk of nonsentinel node metastases in breast cancer. J Natl Cancer Inst 104:1888–1896

    Article  PubMed  Google Scholar 

  35. Straver ME, Meijnen P, van Tienhoven G, van de Velde CJ, Mansel RE, Bogaerts J, Demonty G, Duez N, Cataliotti L, Klinkenbijl J et al (2010) Role of axillary clearance after a tumor-positive sentinel node in the administration of adjuvant therapy in early breast cancer. J Clin Oncol 28(5):731–737

    Article  PubMed  Google Scholar 

  36. Specht MC, Kattan MW, Gonen M, Fey J, Van Zee KJ (2005) Predicting nonsentinel node status after positive sentinel lymph biopsy for breast cancer: clinicians versus nomogram. Ann Surg Oncol 12(8):654–659

    Article  PubMed  Google Scholar 

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Acknowledgments

Tuomo J. Meretoja was supported by grants from the Helsinki University Central Hospital Research Fund, Academy of Finland, Orion-Farmos Research Foundation and Emil Aaltonen’s Foundation.

Conflict of interest

  The authors declare that they have no conflicts of interest.

Ethical standard

  This study complies with the current law of all the countries in which the patients were treated.

Author information

Authors and Affiliations

  1. Breast Surgery Unit, Helsinki University Central Hospital, P.O. Box 140, 00029 HUS, Helsinki, Finland

    Tuomo J. Meretoja & M. H. K. Leidenius

  2. Department of Surgery, St Helens Teaching Hospital, St Helens, UK

    R. A. Audisio

  3. Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland

    P. S. Heikkilä

  4. Department of Pathology, Bács-Kiskun County Teaching Hospital, Kecskemet, Hungary

    R. Bori, I. Sejben & G. Cserni

  5. Department of Pathology, Medical University of Graz, Graz, Austria

    P. Regitnig

  6. Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria

    G. Luschin-Ebengreuth

  7. Department of Surgical Oncology, Institute of Oncology, Ljubljana , Slovenia

    J. Zgajnar & A. Perhavec

  8. Department of Pathology, Institute of Oncology, Ljubljana, Slovenia

    B. Gazic

  9. Department of Surgery, University of Szeged, Szeged, Hungary

    G. Lázár & T. Takács

  10. Department of Pathology, University of Szeged, Szeged, Hungary

    B. Kővári & G. Cserni

  11. Department of Breast Surgery, Lancashire Teaching Hospitals, Chorley, UK

    Z. A. Saidan & R. M. Nadeem

  12. Breast Unit Azienda Ospedaliera Città della Salute e della Scienza of Torino, Department of Medical Sciences, University of Torino, Turin, Italy

    I. Castellano & A. Sapino

  13. Section of Pathological Anatomy, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy

    S. Bianchi & V. Vezzosi

  14. Department of Gynecology and Obstetrics, Lariboisiere Hospital, Paris , France

    E. Barranger & R. Lousquy

  15. Department of Pathology, O.I.R.M.-Sant‘Anna Hospital, Turin, Italy

    R. Arisio

  16. Section of Anatomic Pathology at Bellaria Hospital, Department of Biomedical Sciences and Neuromotory Disorders, University of Bologna, Bologna, Italy

    M. P. Foschini

  17. Department of Breast Surgery, Kyorin University School of Medicine, Tokyo, Japan

    S. Imoto

  18. Department of Pathology, Kyorin University School of Medicine, Tokyo, Japan

    H. Kamma

  19. Department of Breast Surgery, Copenhagen University Hospital, Copenhagen, Denmark

    T. F. Tvedskov

  20. Danish Breast Cancer Cooperative Group, Copenhagen University Hospital, Copenhagen, Denmark

    M.-B. Jensen

Authors
  1. Tuomo J. Meretoja
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  2. R. A. Audisio
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  3. P. S. Heikkilä
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  4. R. Bori
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  5. I. Sejben
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  6. P. Regitnig
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  7. G. Luschin-Ebengreuth
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  8. J. Zgajnar
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  9. A. Perhavec
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  10. B. Gazic
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  11. G. Lázár
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  12. T. Takács
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  13. B. Kővári
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  14. Z. A. Saidan
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  15. R. M. Nadeem
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  16. I. Castellano
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  17. A. Sapino
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  18. S. Bianchi
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  19. V. Vezzosi
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  20. E. Barranger
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  21. R. Lousquy
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  22. R. Arisio
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  23. M. P. Foschini
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  24. S. Imoto
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  25. H. Kamma
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  26. T. F. Tvedskov
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  27. M.-B. Jensen
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  28. G. Cserni
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  29. M. H. K. Leidenius
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Corresponding author

Correspondence to Tuomo J. Meretoja.

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Meretoja, T.J., Audisio, R.A., Heikkilä, P.S. et al. International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases. Breast Cancer Res Treat 138, 817–827 (2013). https://doi.org/10.1007/s10549-013-2468-3

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  • DOI: https://doi.org/10.1007/s10549-013-2468-3

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