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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2015 | Research

Elaboration of a nomogram to predict non sentinel node status in breast cancer patients with positive sentinel node, intra-operatively assessed with one step nucleic acid amplification method

Authors: F. Di Filippo, D. Giannarelli, C. Bouteille, L. Bernet, R. Cano, G. Cunnick, A. Sapino

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2015

Abstract

Backgrounds

Tumor-positive sentinel node(SLN) biopsy results in a risk of nonsentinel node metastases in case of micro and macro metastases ranging from 20 to 50 %, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections.

Thus, the development of a mathematical model for predicting patient-specific risk of non sentinel node(NSLN) metastases is strongly warranted.

Methods

The following parameters were recorded:

Clinical: hospital, age, medical record number
Bio-pathological: tumor (T) size, grading (G), multifocality, histological type, LVI, ER-PR status, HER-2, ki67, molecular classification (luminal A, luminal B, HER2 like, triple negative)
Sentinel and nonsentinel lymph node related: number of removed SLNs, number of positive and negative SLNs, copy number of positive sentinel nodes, ratio: number of positive SLNs to number of removed SLNs, number of removed and number of positive nodes after ALND. A total of 2460 patients have been included in the database.

All the patients have been provided by the authors of this paper.

Results

Multivariate logistic regression analysis demonstrated that only the number of a CK19 mRNA copies (p < 0.0001), T size (p < 0.0001) and LVI (p < 0.0001) were associated with NSN metastases.

The discrimination of the model, quantified with the area under the receiver operating characteristics curve, was 0.71 (95 %, C.I. 0.69–0.73), thus confirming a good level of reliability.

Conclusions

The nomogram may be employed by the surgeon as a decision making tool on whether to perform an intraoperative axillary lymph node dissection on breast cancer patients with SLN positive.

The large population employed and the standardized method of measuring the value of CK19 mRNA copies are appropiate prerequisites for a reliable nomogram.

Piscitelli P, Barba M, Crespi M, Di Maio M, Santoriello A, D’Aiuto M, et al. The burden of breast cancer in Italy: mastectomies and quadrantectomies performed between 2001 and 2008 based on nationwide hospital discharge records. J Exp Clin Cancer Res. 2012;31:96.PubMedCentralCrossRefPubMed

Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, et al. Sentinel-lymph-node biopsy as a staging procedure in breast cancer: update of a randomised controlled study. Lancet Oncol. 2006;7:983–90.CrossRefPubMed

Lyman GH, Giuliano AE, Somerfield MR, Benson 3rd AB, Bodurka DC, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol. 2005;23:7703–20.CrossRefPubMed

Fleissig A, Fallowfield LJ, Langridge CI, Johnson L, Newcombe RG, Dixon JM, et al. Post-operative arm morbidity and quality of life. Results of the ALMANAC randomised trial comparing sentinel node biopsy with standard axillary treatment in the management of patients with early breast cancer. Breast Cancer Res Treat. 2006;95:279–93.CrossRefPubMed

Bolster MJ, Peer PG, Bult P, Thunnissen FB, Schapers RF, Meijer JW, et al. Risk factors for non-sentinel lymph node metastases in patients with breast cancer. The outcome of a multi-institutional study. Ann Surg Oncol. 2007;14(1):181–9. Epub 2006 Oct 7.CrossRefPubMed

Fleming FJ, Kavanagh D, Crotty TB, Quinn CM, McDermott EW, O’Higgins N, et al. Factors affecting metastases to non-sentinel lymph nodes in breast cancer. J Clin Pathol. 2004;57(1):73–6.PubMedCentralCrossRefPubMed

Visser M, Jiwa M, Horstman A, Brink AA, Pol RP, van Diest P, et al. Intra-operative rapid diagnostic ethod based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer. Int J Cancer. 2008;122:2562–7.PubMedCentralCrossRefPubMed

Schem C, Maass N, Bauerschlag DO, Carstensen MH, Löning T, Roder C, et al. One-step nucleic acid amplification-a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group. Virchows Arch. 2009;454:203–10.CrossRefPubMed

Tamaki Y, Akiyama F, Iwase T, Kaneko T, Tsuda H, et al. 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. 2009;15:2879–84.CrossRefPubMed

10.

Tsujimoto M, Nakabayashi K, Yoshidome K, Kaneko T, Iwase T, Akiyama F, et al. One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res. 2007;13:4807–16.CrossRefPubMed

11.

Buglioni S, Di Filippo F, Terrenato I, Casini B, Gallo E, Marandino F, et al. Quantitative molecular analysis of sentinel lymph node may be predictive of axillary node status in breast cancer classified by molecular subtypes. PLoS One. 2013;8(3), e58823.PubMedCentralCrossRefPubMed

12.

Ianosos A, Schrg D, Ray GV, Panageas KS. How to build and interprate a nomogram for cancer program. J Clin Oncol. 2008;16:1364–70.CrossRef

13.

Chen X, Sun L, Cong Y, Zhang T, Lin Q, Meng Q, et al. Baseline staging tests based on molecular subtype is necessary for newly diagnosed breast cancer. J Exp Clin Cancer Res. 2014;33:28.PubMedCentralCrossRefPubMed

14.

Jiang Z, Guo J, Shen J, Jin M, Xie S, Wang L. The role of estrogen receptor alpha in mediating chemoresistance in breast cancer cells. J Exp Clin Cancer Res. 2012;31:42.PubMedCentralCrossRefPubMed

15.

Degnim AC, Reynolds C, Pantvaidya G, Zakaria S, Hoskin T, Barnes S, et al. Nonsentinel node metastasis in breast cancer patients: assessment of an existing and a new predictive nomogram. Am J Surg. 2005;190:543–50.CrossRefPubMed

16.

Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, 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. N. Lancet Oncol. 2010;11(10):927–33.PubMedCentralCrossRefPubMed

17.

Veronesi U, Viale G, Paganelli G, Zurrida S, Luini A, Galimberti V, et al. Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg. 2010;251(4):595–600.CrossRefPubMed

18.

Lyman GH, Temin S, Edge SB, Newman LA, Turner RR, Weaver DL, et al. Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2014;32(13):1365–83.CrossRefPubMed

19.

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.CrossRefPubMed

20.

Latosinsky S, Berrang TS, Cutter CS, George R, Olivotto I, Julian TB, et al. Axillary dissection versus no axillary dissection in women with invasive breast cancer and sentinel node metastasis. J Can Chir, vol 55, N°1 fevrier 2012.

21.

Hoffmann J, Souchon R, Lebeau A, Öhlschlegel C, Gruber G, Rageth C, et al. German, Austrian and Swiss consensus conference on the diagnosis and local treatment of the axilla in breast cancer. AGO; DGS; SGS; ÖGS. Eur J Cancer. 2013;49(10):2277–83.CrossRefPubMed

22.

Galimberti V, Cole BF. Axillary versus sentinel-lymph-node dissection for micrometastatic breast cancer--authors’ reply. Lancet Oncol. 2013;14(7):e251–2.CrossRefPubMed

23.

Rahusen FD, Torrenga H, van Diest PJ, Pijpers R, van der Wall E, Licht J, et al. Predictive factors for metastatic involvement of nonsentinel nodes in patients with breast cancer. Arch Surg. 2001;136:1059e63.CrossRef

24.

Viale G, Maiorano E, Mazzarol G, Zurrida S, Galimberti V, Luini A, et al. Histologic detection and clinical implications of micrometastasis in axillary sentinel lymph nodes for patients with breast carcinoma. Cancer. 2001;92:1378e84.CrossRef

25.

Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233–41.CrossRefPubMed

26.

Pepels MJ, de Boer M, Bult P, van Dijck JA, van Deurzen CH, Menke-Pluymers MB, et al. Regional recurrence in breast cancer patients with sentinel node micrometastases and isolated tumor cells. Ann Surg. 2012;255(1):116–21.CrossRefPubMed

27.

Mittendorf EA, Hunt KK, Boughey JC, Bassett R, Degnim AC, Harrell R, et al. 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. 2012;255(1):109–15.CrossRefPubMed

28.

Houvenaeghel G, Nos C, Mignotte H, Classe JM, Giard S, Rouanet P, et al. Micrometastases in sentinel lymph node in a multicentric study: predictive factors of nonsentinel lymph node involvement. Groupe des Chirurgiens de la Federation des Centres de Lutte Contre le Cancer. J Clin Oncol. 2006;24:1814–22.CrossRefPubMed

29.

Cserni G, Gregori D, Merletti F, Sapino A, Mano MP, Ponti A, et al. Meta-analysis of non-sentinel node metastases associated with micrometastatic sentinel nodes in breast cancer. Br J Surg. 2004;91:1245e52.CrossRef

30.

Wong SL, Edwards MJ, Chao C, Tuttle TM, Noyes RD, Woo C, et al. Predicting the status of the nonsentinel axillary nodes. Arch Surg. 2001;136:563–8.CrossRefPubMed

31.

Reynolds C, Mick R, Donohue JH, Grant CS, Farley DR, Callans LS, et al. Sentinel lymph node biopsy with metastasis: can axillary dissection be avoided in some patients with breast cancer? J Clin Oncol. 1999;17:1720–6.PubMed

32.

Joseph KA, El-Tamer M, Komenaka I, Troxel A, Ditkoff BA, Schnabel F. Predictors of nonsentinel node metastasis in patients with breast cancer after sentinel node metastasis. Arch Surg. 2004;139:648–51.CrossRefPubMed

33.

Turner RR, Chu K, Qi K, Hansen NM, Glass EC, Giuliano AE. Pathologic features associated with nonsentinel lymph node metastases in patients with metastatic breast carcinoma in a sentinel lymph node. Cancer. 2000;89:574–81.CrossRefPubMed

34.

Kamath VJ, Giuliano R, Dauway EL, Cantor A, Berman C, Ku NN, et al. Characteristics of the sentinel lymph node in breast cancer predict further involvement of higher-echelon nodes in the axilla: a study to evaluate the need for complete axillary lymph node dissection. Arch Surg. 2001;136:688–92.CrossRefPubMed

35.

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

36.

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

37.

Coutant C, Olivier C, Lambaudie E, Fondrinier E, Marchal F, Guillemin F, et al. Comparison of models to predict nonsentinel lymph node status in breast cancer patients with metastatic sentinel lymph nodes: a prospective multicenter study. J Clin Oncol. 2009;27(17):2800–8.CrossRefPubMed

38.

Van Zee KJ, Manasseh DM, Bevilacqua JL, Boolbol SK, Fey JV, Tan LK, et al. A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy. Ann Surg Oncol. 2003;10:1140–51.CrossRefPubMed

39.

Kohrt HE, Olshen RA, Bermas HR, Goodson WH, Wood DJ, Henry S, et al. New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients. BMC Cancer. 2008;8:66.PubMedCentralCrossRefPubMed

40.

Pal A, Provenzano E, Duffy SW, Pinder SE, Purushotham AD. A model for predicting non-sentinel lymph node metastatic disease when the sentinel lymph node is positive. Br J Surg. 2008;95:302–9.CrossRefPubMed

41.

Barranger E, Coutant C, Flahault A, Delpech Y, Darai E, Uzan S, et al. An axille scoring system to predict non-sentinel lymph node status in breast cancer patients with sentinel lymph node involvement. Breast Cancer Res. 2005;91:113–9.CrossRef

42.

Van la Parra RF, Peer PG, Ernst MF, Bosscha K. Meta-analysis of predictive factors for non-sentinel lymph node metastases in breast cancer patients with a positive SLN. Eur J Surg Oncol. 2011;37(4):290–9.CrossRef

43.

Koca B, Kuru B, Ozen N, Yoruker S, Beh Y. A breast cancer nomogram for prediction of non-sentinel node metastasis- validation of fourteen existing models. Asian Pac J Cancer Prev. 2014;15(3):1481–8.CrossRefPubMed

Title: Elaboration of a nomogram to predict non sentinel node status in breast cancer patients with positive sentinel node, intra-operatively assessed with one step nucleic acid amplification method
Authors: F. Di Filippo
D. Giannarelli
C. Bouteille
L. Bernet
R. Cano
G. Cunnick
A. Sapino
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2015
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-015-0246-2

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Abstract

Backgrounds

Methods

Results

Conclusions

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