Axillary Nodal Metastases in Italian Early Breast Cancer Patients with Positive Sentinel Lymph Node: Can Axillary Node Dissection be Avoided by using Predictive Nomograms?

Abstract

Aims and Background

Clinical guidelines recommend axillary lymph node dissection (ALND) in cases of metastatic sentinel lymph node (SNL) in patients with clinically node-negative early breast cancer. However, a relevant number of ALND could be avoided in a subset of patients in whom the risk of non-SNL metastases is low. In order to define this population, several authors have proposed mathematical models, which have been validated in many studies. These studies reached different conclusions regarding which model demonstrated the best statistical discrimination power, mainly due to differences in clinical and pathologic variables used, and particularly differences in the number of dissected SLNs.

Methods

We retrospectively reviewed clinically node-negative patients who underwent ALND in our surgical ward after the diagnosis of breast cancer metastases on SLN biopsy from January 2000 to December 2012. The predictive accuracy of the widely used nomograms to predict the risk of additional nodal disease in our patients with SLN breast cancer metastases was measured by receiver operating characteristic curve. We then attempted to develop a new nomogram by analyzing the dataset.

Results

A total of 105 patients were included in this study, with ratio of metastatic lymph node/removed lymph node of about 0.89; we found axillary nodal metastases on ALND in only 31 patients (29.5%). Applied to our dataset, Mayo nomogram showed the best area under the receiving operator characteristic curve (0.74) followed by our model (0.71). Instead, the Memorial Sloan-Kettering model showed poor discrimination, as did Tenon (0.56).

Conclusions

Based on our data, we cannot recommend the clinical use of validated predictive nomograms in order to avoid ALND. We suggest setting up a multicenter Italian study to build a model specific to our setting and based on larger series.

Keywords

Breast cancer Nomogram Nonsentinel lymph node Predictive models

Get full access to this article

View all access options for this article.

References

Salem

Sentinel lymph node biopsy in breast cancer: a comprehensive literature review. J Surg Educ. 2009; 66(5): 267–275.

Veronesi

Viale

Paganelli

Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg. 2010; 251(4): 595–600.

Lyman

G.H.

Giuliano

A.E.

Somerfield

M.R.

; American Society of Clinical Oncology. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol. 2005; 23(30): 7703–7720.

Turner

R.R.

Chu

K.U.

Pathologic features associated with nonsentinel lymph node metastases in patients with metastatic breast carcinoma in a sentinel lymph node. Cancer. 2000; 89(3): 574–581.

Nos

Harding-MacKean

Fréneaux

Prediction of tumour involvement in remaining axillary lymph nodes when the sentinel node in a woman with breast cancer contains metastases. Br J Surg. 2003; 90(11): 1354–1360.

Giuliano

A.E.

McCall

Beitsch

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(3): 426–432, discussion 432–433.

Galimberti

Cole

B.F.

Zurrida

; International Breast Cancer Study Group Trial 23–01 investigators. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23–01): a phase 3 randomised controlled trial. Lancet Oncol. 2013; 14(4): 297–305.

Lyman

G.H.

Temin

Edge

S.B.

; American Society of Clinical Oncology Clinical Practice. 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): 1365–1383.

Van Zee

K.J.

Manasseh

D.M.

Bevilacqua

J.L.

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(10): 1140–1151.

10.

Degnim

A.C.

Reynolds

Pantvaidya

Nonsentinel node metastasis in breast cancer patients: assessment of an existing and a new predictive nomogram. Am J Surg. 2005; 190(4): 543–550.

11.

Pal

Provenzano

Duffy

S.W.

Pinder

S.E.

Purushotham

A.D.

A model for predicting non-sentinel lymph node metastatic disease when the sentinel lymph node is positive. Br J Surg. 2008; 95(3): 302–309.

12.

Kohrt

H.E.

Olshen

R.A.

Bermas

H.R.

; Bay Area SLN Study. New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients. BMC Cancer. 2008; 8(1): 66.

13.

Hwang

R.F.

Krishnamurthy

Hunt

K.K.

Clinicopathologic factors predicting involvement of nonsentinel axillary nodes in women with breast cancer. Ann Surg Oncol. 2003; 10(3): 248–254.

14.

Barranger

Coutant

Flahault

Delpech

Darai

Uzan

An axilla scoring system to predict non-sentinel lymph node status in breast cancer patients with sentinel lymph node involvement. Breast Cancer Res Treat. 2005; 91(2): 113–119.

15.

Gur

A.S.

Unal

Ozbek

; Turkish Federation of Breast Disease Associations Protocol MF08-01 investigators. 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. 2010; 36(1): 30–35.

16.

Lombardi

Maggi

Lo Russo

Non-sentinel lymph node metastases in breast cancer patients with a positive sentinel lymph node: validation of five nomograms and development of a new predictive model. Tumori. 2011; 97(6): 749–755.

17.

Mittendorf

E.A.

Hunt

K.K.

Boughey

J.C.

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): 109–115.

18.

Coutant

Olivier

Lambaudie

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): 2800–2808.

19.

Sasada

Kataoka

Shigematsu

Three models for predicting the risk of non-sentinel lymph node metastasis in Japanese breast cancer patients. Breast Cancer. 2014; 21(5): 571–575.

20.

Tanaka

Sato

Fujioka

Takahashi

Kimura

Iwamoto

Validation of online calculators to predict the non-sentinel lymph node status in sentinel lymph node-positive breast cancer patients. Surg Today. 2013; 43(2): 163–170.

21.

Hidar

Harrabi

Benregaya

Validation of nomograms to predict the risk of non-sentinels lymph node metastases in North African Tunisian breast cancer patients with sentinel node involvement. Breast. 2011; 20(1): 26–30.

22.

Moghaddam

Falzon

Fulford

Williams

N.R.

Keshtgar

M.R.

Comparison of three mathematical models for predicting the risk of additional axillary nodal metastases after positive sentinel lymph node biopsy in early breast cancer. Br J Surg. 2010; 97(11): 1646–1652.

23.

D'Eredita

Troilo

V.L.

Fischetti

Rubini

Berardi

Comparison of two models for predicting non-sentinel lymph node metastases in sentinel lymph node-positive breast cancer patients. Updates Surg. 2011; 63(3): 163–170.

24.

Cho

Han

Lee

J.W.

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. 2008; 15(8): 2278–2286.

25.

Coufal

Pavlfk

Fabian

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. 2009; 15(4): 733–740.

26.

Berrang

T.S.

Lesperance

Truong

P.T.

Walter

Hayashi

A.H.

Olivotto

I.A.

Which prediction models best identify additional axillary disease after a positive sentinel node biopsy for breast cancer?

Breast Cancer Res Treat. 2012; 133(2): 695–702.

27.

Cripe

M.H.

Beran

L.C.

Liang

W.C.

Sickle-Santanello

B.J.

The likelihood of additional nodal disease following a positive sentinel lymph node biopsy in breast cancer patients: validation of a nomogram. Am J Surg. 2006; 192(4): 484–487.

28.

Ponzone

Maggiorotto

Mariani

Comparison of two models for the prediction of nonsentinel node metastases in breast cancer. Am J Surg. 2007; 193(6): 686–692.

29.

Poirier

Sideris

Dubé

Drolet

Meterissian

S.H.

Analysis of clinical applicability of the breast cancer nomogram for positive sentinel lymph node: the Canadian experience. Ann Surg Oncol. 2008; 15(9): 2562–2567.

30.

Scow

J.S.

Degnim

A.C.

Hoskin

T.L.

Reynolds

Boughey

J.C.

Assessment of the performance of the Stanford Online Calculator for the prediction of nonsentinel lymph node metastasis in sentinel lymph node-positive breast cancer patients. Cancer. 2009; 115(18): 4064–4070.

31.

Gur

A.S.

Unal

Johnson

Predictive probability of four different breast cancer nomograms for nonsentinel axillary lymph node metastasis in positive sentinel node biopsy. J Am Coll Surg. 2009; 208(2): 229–235.

32.

van la Parra

R.F.

Ernst

M.F.

Bevilacqua

J.L.

Validation of a nomogram to predict the risk of nonsentinel lymph node metastases in breast cancer patients with a positive sentinel node biopsy: validation of the MSKCC breast nomogram. Ann Surg Oncol. 2009; 16(5): 1128–1135.

33.

D'Eredit

Troilo

V.L.

Giardina

Sentinel lymph node micrometastasis and risk of non-sentinel lymph node metastasis: validation of two breast cancer nomograms. Clin Breast Cancer. 2010; 10(6): 445–451.

34.

Moghaddam

Falzon

Fulford

Williams

N.R.

Keshtgar

M.R.

35.

Hessman

C.J.

Naik

A.M.

Kearney

N.M.

Comparative validation of online nomograms for predicting nonsentinel lymph node status in sentinel lymph node-positive breast cancer. Arch Surg. 2011; 146(9): 1035–1040.

36.

Orsoni

Clerc

Golfier

Cortet

Raudrant

Krauth

J.S.

Axillary lymph node dissection in the case of sentinel lymph node micrometastatic invasion: evaluation of three predictive models. Eur J Obstet Gynecol Reprod Biol. 2011; 158(2): 334–337.

37.

Andersson

Frisell

de Boniface

Bergkvist

Prediction of non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastases: evaluation of the Tenon score. Breast Cancer. 2012; 6: 31–38.

38.

Sasada

Murakami

Kataoka

Memorial Sloan-Kettering Cancer Center nomogram to predict the risk of non-sentinel lymph node metastasis in Japanese breast cancer patients. Surg Today. 2012; 42(3): 245–249.

39.

Dauphine

C.E.

Haukoos

J.S.

Vargas

M.P.

Isaac

N.M.

Khalkhali

Vargas

H.I.

Evaluation of three scoring systems predicting non sentinel node metastasis in breast cancer patients with a positive sentinel node biopsy. Ann Surg Oncol. 2007; 14(3): 1014–1019.

40.

Zgajnar

Perhavec

Hocevar

Low performance of the MSKCC nomogram in preoperatively ultrasonically negative axillary lymph node in breast cancer patients. J Surg Oncol. 2007; 96(7): 547–553.

41.

Klar

Jochmann

Foeldi

The MSKCC nomogram for prediction the likelihood of non-sentinel node involvement in a German breast cancer population. Breast Cancer Res Treat. 2008; 112(3): 523–531.

42.

Coutant

Rouzier

Fondrinier

Validation of the Tenon breast cancer score for predicting non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastasis: a prospective multicenter study. Breast Cancer Res Treat. 2009; 113(3): 537–543.

43.

Sanjuán

Escaramfs

Vidal-Sicart

Predicting nonsentinel lymph node status in breast cancer patients with sentinel lymph node involvement: evaluation of two scoring systems. Breast J. 2010; 16(2): 134–140.

44.

van den Hoven

Kuijt

G.P.

Voogd

A.C.

van Beek

M.W.

Roumen

R.M.

Value of Memorial Sloan-Kettering Cancer Center nomogram in clinical decision making for sentinel lymph node-positive breast cancer. Br J Surg. 2010; 97(11): 1653–1658.

45.

Tan

E.Y.

Chen

J.J.

Predictors of nonsentinel nodal involvement to aid intraoperative decision making in breast cancer patients with positive sentinel lymph nodes. ISRN Oncol. 2011; 2011: 539503.

46.

Chen

J.Y.

Chen

J.J.

Yang

B.L.

Predicting sentinel lymph node metastasis in a Chinese breast cancer population: assessment of an existing nomogram and a new predictive nomogram. Breast Cancer Res Treat. 2012; 135(3): 839–848.

47.

Zhu

Jin

Which nomogram is best for predicting non-sentinel lymph node metastasis in breast cancer patients? A meta-analysis. Breast Cancer Res Treat. 2013; 137(3): 783–795.

48.

Koca

Kuru

Ozen

Yoruker

Bek

A breast cancer nomogram for prediction of non-sentinel node metastasis: validation of fourteen existing models. Asian Pac J Cancer Prev. 2014; 15(3): 1481–1488.

49.

Bertozzi

Londero

A.P.

Giacomuzzi

Applicability of two different validated models to predict axillary non-sentinel lymph node status by sentinel node biopsy in a single Italian center. Breast Cancer. 2013; (Jul): 6.

50.

Kuo

Y.L.

Chen

W.C.

Yao

W.J.

Validation of Memorial Sloan-Kettering Cancer Center nomogram for prediction of non-sentinel lymph node metastasis in sentinel lymph node positive breast cancer patients an international comparison. Int J Surg. 2013; 11(7): 538–543.

51.

Al-Masri

Darwazeh

El-Ghanem

Hamdan

Sughayer

Assessment of an existing and modified model for predicting non sentinel lymph node metastasis in breast cancer patients with positive sentinel node biopsy. Gulf J Oncolog. 2013; 1(13): 15–22.

52.

Amadori

Conte

Di Blasio

Servizio Presidi Ospedalieri, Servizio Sanità Pubblica. Raccomandazioni per la procedura chirurgica della biopsia del linfonodo sentinella (SN) ascellare in Raccomandazioni su alcuni aspetti riguardanti le procedure di Anatomia Patologica, Chirurgiche e per la Terapia Medica adiuvante nella tecnica del Linfonodo Sentinella nel carcinoma della mammella. Recommendations of the Emilia Romagna Regional Government, 2007. Available at: http://assr.regione.emilia-romagna.it/it/servizi/pubblicazioni/rapporti-documen-ti/racc-linfonodo-sentinella.

53.

AAVV. “Biopsia del Linfonodo sentinella” in F.O.N.CA.M. Guidelines 2012. Available at: http://www.senologia.it/images/pdf/BLS%202012.pdf.

54.

Alberta Provincial Breast Tumour Team. Sentinel lymph node biopsy and axillary node dissection in early stage breast cancer (Clinical Practice Guideline; no. BR-004). Edmonton: Alberta Health Services, Cancer Care; 2012.

55.

Kobayashi

Shiraishi

Iwase

Ohtomo

Nakagawa

Omission of axillary lymph node dissection for clinically node negative early-stage breast cancer patients. Breast Cancer. 2014; (Apr): 23.

56.

Janni

Kühn

Schwentner

Kreienberg

Fehm

Wöckel

Sentinel node biopsy and axillary dissection in breast cancer: the evidence and its limits. Dtsch Arztebl Int. 2014; 111(14): 244–249.

57.

Unal

Gur

A.S.

Beriwal

Predicting likelihood of having four or more positive nodes in patient with sentinel lymph node-positive breast cancer: a nomogram validation study. Int J Radiat Oncol Biol Phys. 2009; 75(4): 1035–1040.

58.

AAVV. “La radioterapia nel trattamento del carcinoma mammario” in F.O.N.CA.M. Guidelines, 2012. Available at: http://www.senologia.it/images/pdf/Radioterapia%20FONCAM%202012.pdf.