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Nomogram including the total tumoral load in the sentinel nodes assessed by one-step nucleic acid amplification as a new factor for predicting nonsentinel lymph node metastasis in breast cancer patients

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Abstract

Several models have been developed to predict non-sentinel nodes (NSLN) metastasis in patients with a positive sentinel node (SLN) that incorporates a standard pathology examination of the SLN. It has been reported that total tumoral load (TTL) in the SLNs assessed by one-step nucleic acid amplification (OSNA) is a predictive factor for additional NSLN metastasis in the axillary lymph node dissection (ALND). The objective was to develop a nomogram that predicts patient´s risk of additional NSLN metastasis incorporating TTL in the SLNs assessed by OSNA. Six hundred and ninety-seven consecutive patients with positive SLN evaluation by OSNA and a completion ALND were recruited. Pathologic features of the primary tumor and SLN metastases, including TTL were collected. Multivariate logistic regression identified factors predictive of non-SLN metastasis. A nomogram was developed with these variables and validated in an external cohort. On multivariate logistic regression analysis, tumor size, number of affected SLN, Her2 overexpression, lymphovascular invasion, and TTL were each associated with the likelihood of additional NSLN metastasis (p < 0.05). The overall predictive accuracy of the nomogram, as measured by the AUC was 0.7552 (95 %CI 0.7159–0.7945). When applied to the external cohort the nomogram was accurate with an AUC = 0.678 (95 %CI 0.621–0.736). This novel nomogram that incorporates TTL assessed by OSNA performs well and may help clinicians to make decisions about ALND for individual patients. Moreover, the standardization of pathologic assessment by OSNA may help to achieve interinstitutional reproducibility among nomograms.

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References

  1. Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Constantino JP et al (2010) 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. Lancet Oncol 11(10):927–933

    Article  PubMed Central  PubMed  Google Scholar 

  2. Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V et al (2006) Sentinel-lymph-node biopsy as a staging procedure in breast cancer: update of a randomised controlled study. Lancet Oncol 7(12):983–990

    Article  PubMed  Google Scholar 

  3. Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM 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 98:599–600

    Article  PubMed  Google Scholar 

  4. Abdessalam SF, Zervos EE, Prasad M, Farrar WB, Yee LD, Walker MJ et al (2001) Predictors of positive axillary lymph nodes after sentinel lymph node biopsy in breast cancer. Am J Surg 182:316–320

    Article  CAS  PubMed  Google Scholar 

  5. Hwang RF, Gonzalez-Angulo AM, Yi M, Buchholz TA, Meric-Berstein F, Kuerer HM et al (2007) Low locoregional failure rates in selected breast cancer patients with tumor-positive sentinel lymph nodes who do not undergo completion axillary dissection. Cancer 110(4):723–730

    Article  PubMed  Google Scholar 

  6. Giuliano AE, McCall L, Beitsch P, Whitworth PW, Blumencranz P, Leitch AM et al (2010) Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastasis: the American College of Surgeons Oncology group z0011 randomized trial. Ann Surg 252:426–432

    PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  8. 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 91:113–119

    Article  PubMed  Google Scholar 

  9. 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 70:101–105

    PubMed  Google Scholar 

  10. Degnim AC, Reynolds C, Pantvaidya G, Zakaria S, Hoskin T, Barnes S et al (2005) Nonsentinel node metastasis in breast cancer patients: assessment of an existing and a new predictive nomogram. Am J Surg 190:543–550

    Article  PubMed  Google Scholar 

  11. Kohrt HE, Olshen RA, Bermas HR, Goodson WH, Wood DJ, Henry S 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 Central  PubMed  Google Scholar 

  12. 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 95:302–309

    Article  CAS  PubMed  Google Scholar 

  13. Mittendorf EA, Hunt KK, Boughey JC, Bassett R, Degnim AC, Harrell R et al (2012) Incorporation of sentinel lymph node metastasis size into a nomogram predicting nonsentinel lymph node involvement in breast cancer patients with a positive sentinel lymph node. Ann Surg 255:109–115

    Article  PubMed  Google Scholar 

  14. Bolster MJ, Peer PG, Bult P, Thunnissen FB, Schapers RF, Meijer JW et al (2007) Risk factors for non sentinel lymph node metastases in patients with breast cancer. The outcome of a multi-institutional study. Ann Surg Oncol 14:181–189

    Article  PubMed  Google Scholar 

  15. Ozmen V, Karanlik H, Cabioglu N, Igci A, Kecer M, Asoglu O et al (2006) Factors predicting the sentinel and non sentinel lymph node metastases in breast cancer. Breast Cancer Res Treat 95:1–6

    Article  CAS  PubMed  Google Scholar 

  16. Patani N, Mokbel K (2009) The clinical significance of sentinel lymph node micrometastasis in breast cancer. Breast Cancer Res Treat 114:393–402

    Article  PubMed  Google Scholar 

  17. Castellano I, Macri L, Deambrogio C, Balmativola D, Bussone R, Ala A et al (2011) Reliability of whole sentinel lymph node analysis by one-step nucleic acid amplification for intraoperative diagnosis of breast cancer metastases. Ann Surg 00:1–9

    Google Scholar 

  18. Cserni G (2012) Intraoperative analysis of sentinel lymph nodes in breast cancer by one-step nucleic acid amplification. J Clin Pathol 65(3):193–199

    Article  CAS  PubMed  Google Scholar 

  19. Tsujimoto M, Nakabayashi K, Yoshidome K, Kaneko T, Iwase T, Akiyama F et al (2007) One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res 13:4807–4816

    Article  CAS  PubMed  Google Scholar 

  20. Visser M, Jiwa M, Horstman A, Brink AA, Pol RP, van Diest P et al (2008) Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer. Int J Cancer 122:2562–2567

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Tamaki Y, Akiyama F, Iwase T, Kaneko T, Tsuda H, Sato K, Ueda S et al (2009) Molecular detection of lymph node metastases in breast cancer patients: results of a multicenter trial using the one-step nucleic acid amplification assay. Clin Cancer Res 15:2879–2884

    Article  CAS  PubMed  Google Scholar 

  22. Espinosa-Bravo M, Sansano I, Pérez-Hoyos S, Ramos M, Sancho M, Xercavins J et al (2013) Prediction of non-sentinel lymph node metastasis in early breast cancer by assessing total tumoral load in the sentinel lymph node by molecular assay. Eur J Surg Oncol 39(7):766–773

    Article  CAS  PubMed  Google Scholar 

  23. Peg V, Espinosa-Bravo M, Vieites B, Vilardell F, Antúnez JR, de Salas MS et al (2013) Intraoperative molecular analysis of total tumor load in sentinel lymph node: a new predictor of axillary status in early breast cancer patients. Breast Cancer Res Treat 139(1):87–93

    Article  CAS  PubMed  Google Scholar 

  24. Rubio IT, Aznar F, Lirola J, Peg V, Xervacins J et al (2010) Intraoperative assessment of sentinel lymph nodes after neoadjuvant chemotherapy in patients with breast cancer. Ann Surg Oncol 17(1):235–239

    Article  PubMed  Google Scholar 

  25. Edge SBBD, Compton CC, Fritz AG et al (2010) AJCC cancer staging manual, 7th edn. Springer, New York

    Google Scholar 

  26. Steyerberg EW, Borsboom GJ, van Houwelingen HC, Eijkemans MJ, Habbema JD (2004) Validation and updating of predictive logistic regression models: a study on sample size and shrinkage. Stat Med 23:2567–2586

    Article  PubMed  Google Scholar 

  27. Feldman S, Krishnamurthy S, Gillanders W, Gittleman M, Beitsch PD, Young PR et al (2011) A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes. Cancer 117(12):2599–2607

    Article  CAS  PubMed  Google Scholar 

  28. Osako T, Iwase T, Kimura K, Horii R, Akiyama F (2013) Sentinel tumor burden quantified based on cytokeratin 19 mRNA copy number predicts non sentinel node metastases in breast cáncer: molecular whole-node analysis of all removed nodes. Eur J Cancer 49(6):1187–1196

    Article  CAS  PubMed  Google Scholar 

  29. Meretoja TJ, Leidenius MH, Heikkila PS, Boross G, Sejben I, Regitnig P et al (2012) International multicenter tool to predict the risk of nonsentinel node metastasis in breast cancer. J Natl Cancer Inst 104(24):1888–1896

    Article  PubMed  Google Scholar 

  30. Crabb SJ, Cheand MC, Leung S, Immonen T, Nielsen TO, Huntsman DD et al (2008) Basal breast cancer molecular subtype predicts for lower incidence of axillary lymph node metàstasis in primary breast cancer. Clin Breast Cancer 8:249–256

    Article  PubMed  Google Scholar 

  31. Van Calster B, Vanden Bempt I, Drijkoningen M, Pochet N, Cheng J, Van Huffel S et al (2009) Axillary lymph node status of operable breast càncers by combined steroid receptor and Her2 status: triple positive tumors are more likely lymph node positive. Breast Cancer Res Treat 113:181–187

    Article  CAS  PubMed  Google Scholar 

  32. Jones T, Neboori H, Wu H, Yang Q, Haffty BG, Evans S et al (2013) Are breast cancer subtypes prognostic for nodal involvement and associated with clinicopathologic features at presentation in early stage breast càncer? Ann Surg Oncol 20(9):2866–2872

    Article  PubMed  Google Scholar 

  33. Coutant C, Olivier C, Lambaudie E, Fondrinier E, Marchai F, Guillemin F et al (2009) Comparison of models to predict nonsentinel lymph node status in breast cancer patients with metastatic sentinel lymph nodes: a prospective multicenter study. JCO 27:2800–2808

    Article  Google Scholar 

  34. Klar M, Jochmann A, Foeldi M, Stumpf M, Gitsch G, Stickeler E, Watermann D (2008) The MSKCC nomogram for prediction the likelihood of non sentinel node involvement in a German breast cancer population. Breast Cancer Res Treat 112:523–531

    Article  CAS  PubMed  Google Scholar 

  35. Andersson Y, Frisell J, de Boniface J, Bergkvist L (2012) Prediction of non sentinel node status in breast cancer patients with sentinel lymph node metastases: evaluation of the Tenon Score. Breast Cancer Clin Res 6:31–38

    Article  CAS  Google Scholar 

  36. Specht MC, Kattan MW, Gonen M, Fey J, Van Zee KJ (2005) Predicting nonsentinel node status after positive lymph biopsy for breast cancer: clinicians versus nomogram. Ann Surg Oncol 12(8):654–658

    Article  PubMed  Google Scholar 

  37. Caudle AS, Hunt KK, Tucker SL, Hoffman K, Gainer SM, Lucci A et al (2012) American College of Surgeons Oncology Group (ACOSOG) Z0011: impact on surgeon practice patterns. Ann Surg Oncol 19(10):3144–3151

    Article  PubMed  Google Scholar 

  38. Latosinsky S, Berrang TS, Cutter CS, George R, Olivotto I, Julian TB (2012) Axillary dissection versus non axillary dissection in women with invasive breast cancer and sentinel node metástasis. Can J Surg 55:66–69

    Article  PubMed Central  PubMed  Google Scholar 

  39. Massimino KP, Hessman CJ, Ellis MC, Naik AM, Vetto JT (2012) Impact of American College of Surgeons Oncology Group Z0011 and National Surgical Adjuvant Breast and Bowel Project B-32 trial results on surgeon practice in the Pacific Northwest. Am J Surg 203(5):618–622

    Article  PubMed  Google Scholar 

  40. Loveland-Jones CE, Ruth K, Sigurdson ER, Egleston BL, Boraas M, Bleicher RJ (2014) Patterns of nodal staging during breast conservation surgery in the medicare patient: will the ACOSOG Z0011 trial change the pattern of care? Breast Cancer Res Treat 143(3):571–577

    Article  PubMed  Google Scholar 

  41. Caudle A, Hunt KK, Kuerer HM, Meric-Berstein F, Lucci A, Bedrosian I, Babiera GV et al (2011) Multidisciplinary considerations in the implementation of the findings from the American College of Surgeons Oncology Group (ACOSOG) Z0011 study: a practice-changing trial. Ann Surg Oncol 18(9):2407–2412

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by a grant from the Sysmex Espana S.L. The sponsor had no role in the study design, analysis, or interpretation of the data.

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Correspondence to Isabel T. Rubio.

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Participating investigators (collected data): Paz Santiago, MD, Hospital de A Coruña, La Coruña, Spain; Sofia Pereira, MD, Hospital Virgen de la Macarena, Sevilla, Spain; Octavio Burgues, MD, Hospital Clinico de Valencia, Valencia, Spain; Angeles Torres, MD, Hospital Universitario Rio Hortega, Valladolid, Spain; Irune Ruiz, MD, HU Donostia, San Sebastian, Spain.

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Rubio, I.T., Espinosa-Bravo, M., Rodrigo, M. et al. Nomogram including the total tumoral load in the sentinel nodes assessed by one-step nucleic acid amplification as a new factor for predicting nonsentinel lymph node metastasis in breast cancer patients. Breast Cancer Res Treat 147, 371–380 (2014). https://doi.org/10.1007/s10549-014-3108-2

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  • DOI: https://doi.org/10.1007/s10549-014-3108-2

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