Cancer Res Treat.  2018 Jul;50(3):625-633. 10.4143/crt.2017.089.

Risk Factors for a False-Negative Result of Sentinel Node Biopsy in Patients with Clinically Node-Negative Breast Cancer

• Lee SA
• Lee HM
• Lee HW
• Yang BS
• Park JT
• Ahn SG
• Jeong J
• Kim SI

• KMID: 2417852
• DOI: http://doi.org/10.4143/crt.2017.089

Abstract

PURPOSE
Although sentinel lymph node biopsy (SLNB) can accurately represent the axillary lymph node (ALN) status, the false-negative rate (FNR) of SLNB is the main concern in the patients who receive SLNB alone instead of ALN dissection (ALND).
MATERIALS AND METHODS
We analyzed 1,886 patientswho underwent ALND after negative results of SLNB, retrospectively. A logistic regression analysis was used to identify risk factors associated with a false-negative (FN) result. Cox regression model was used to estimate the hazard ratio of factors affecting disease-free survival (DFS).
RESULTS
Tumor located in the upper outer portion of the breast, lymphovascular invasion, suspicious node in imaging assessment and less than three sentinel lymph nodes (SLNs) were significant independent risk factors for FN in SLNB conferring an adjusted odds ratio of 2.10 (95% confidence interval [CI], 1.30 to 3.39), 2.69 (95% CI, 1.47 to 4.91), 2.59 (95% CI, 1.62 to 4.14), and 2.39 (95% CI, 1.45 to 3.95), respectively. The prognostic factors affecting DFS were tumor size larger than 2 cm (hazard ratio [HR], 1.86; 95% CI, 1.17 to 2.96) and FN of SLNB (HR, 2.51; 95% CI, 1.42 to 4.42) in SLN-negative group (FN and true-negative), but in ALN-positive group (FN and true-positive), FN of SLNB (HR, 0.64; 95% CI, 0.33 to 1.25) did not affect DFS.
CONCLUSION
In patients with risk factors for a FN such as suspicious node in imaging assessment, upper outer breast cancer, less than three harvested nodes, we need attention to find another metastatic focus in non-SLNs during the operation. It may contribute to provide an exact prognosis and optimizing adjuvant treatments.

Keyword

False negative; Sentinel lymph node; Prognosis; Breast neoplasms

MeSH Terms

Biopsy*
Breast Neoplasms*
Breast*
Disease-Free Survival
Humans
Logistic Models
Lymph Nodes
Odds Ratio
Prognosis
Retrospective Studies
Risk Factors*
Sentinel Lymph Node Biopsy

Figure

• 

  Fig. 1. Disease-free survival and overall survival according to the results of sentinel lymph node (LN) biopsy. (A) Disease-free survival analysis between true-negative and false-negative group (p=0.001). (B) Overall survival analysis between true-negative and false-negative group (p=0.312).

Reference

References

1. Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst. 2006; 98:599–609.

2. Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med. 2003; 349:546–53.

3. 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; 251:595–600.

4. Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, 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. Lancet Oncol. 2010; 11:927–33.

5. van der Ploeg IM, Nieweg OE, van Rijk MC, Valdes Olmos RA, Kroon BB. Axillary recurrence after a tumour-negative sentinel node biopsy in breast cancer patients: a systematic review and meta-analysis of the literature. Eur J Surg Oncol. 2008; 34:1277–84.

6. 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; 32:1365–83.

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

8. Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thurlimann B, Senn HJ, et al. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 2009; 20:1319–29.

9. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer, version 3.2014. Fort Washington, PA: National Comprehensive Cancer Network;2014.

10. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. 7th ed. New York: Springer;2010.

11. Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Ashikaga T, et al. Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. Lancet Oncol. 2007; 8:881–8.

12. Martin RC 2nd, Chagpar A, Scoggins CR, Edwards MJ, Hagendoorn L, Stromberg AJ, et al. Clinicopathologic factors associated with false-negative sentinel lymph-node biopsy in breast cancer. Ann Surg. 2005; 241:1005–12.

13. Goyal A, Newcombe RG, Chhabra A, Mansel RE; ALMANAC Trialists Group. Factors affecting failed localisation and false-negative rates of sentinel node biopsy in breast cancer: results of the ALMA-NAC validation phase. Breast Cancer Res Treat. 2006; 99:203–8.

14. Zavagno G, Del Bianco P, Koussis H, Artioli G, Carraro P, De Salvo GL, et al. Clinical impact of false-negative sentinel lymph nodes in breast cancer. Eur J Surg Oncol. 2008; 34:620–5.

15. Wong SL, Edwards MJ, Chao C, Tuttle TM, Noyes RD, Carlson DJ, et al. Sentinel lymph node biopsy for breast cancer: impact of the number of sentinel nodes removed on the false-negative rate. J Am Coll Surg. 2001; 192:684–9.

16. Pecha V, Kolarik D, Kozevnikova R, Hovorkova K, Hrabetova P, Halaska M, et al. Sentinel lymph node biopsy in breast cancer patients treated with neoadjuvant chemotherapy. Cancer. 2011; 117:4606–16.

17. Andersson Y, Frisell J, Sylvan M, de Boniface J, Bergkvist L. Causes of false-negative sentinel node biopsy in patients with breast cancer. Br J Surg. 2013; 100:775–83.

18. Mills P, Sever A, Weeks J, Fish D, Jones S, Jones P. Axillary ultrasound assessment in primary breast cancer: an audit of 653 cases. Breast J. 2010; 16:460–3.

19. Deurloo EE, Tanis PJ, Gilhuijs KG, Muller SH, Kroger R, Peterse JL, et al. Reduction in the number of sentinel lymph node procedures by preoperative ultrasonography of the axilla in breast cancer. Eur J Cancer. 2003; 39:1068–73.

20. Leenders MW, Broeders M, Croese C, Richir MC, Go HL, Langenhorst BL, et al. Ultrasound and fine needle aspiration cytology of axillary lymph nodes in breast cancer. to do or not to do? Breast. 2012; 21:578–83.

21. Valente SA, Levine GM, Silverstein MJ, Rayhanabad JA, Weng-Grumley JG, Ji L, et al. Accuracy of predicting axillary lymph node positivity by physical examination, mammography, ultrasonography, and magnetic resonance imaging. Ann Surg Oncol. 2012; 19:1825–30.

22. Hyun SJ, Kim EK, Yoon JH, Moon HJ, Kim MJ. Adding MRI to ultrasound and ultrasound-guided fine-needle aspiration reduces the false-negative rate of axillary lymph node metastasis diagnosis in breast cancer patients. Clin Radiol. 2015; 70:716–22.

23. An YS, Lee DH, Yoon JK, Lee SJ, Kim TH, Kang DK, et al. Diagnostic performance of 18F-FDG PET/CT, ultrasonography and MRI: detection of axillary lymph node metastasis in breast cancer patients. Nuklearmedizin. 2014; 53:89–94.

24. Wang Y, Dong H, Wu H, Zhang L, Yuan K, Chen H, et al. Improved false negative rate of axillary status using sentinel lymph node biopsy and ultrasound-suspicious lymph node sampling in patients with early breast cancer. BMC Cancer. 2015; 15:382.

25. Tafra L, Lannin DR, Swanson MS, Van Eyk JJ, Verbanac KM, Chua AN, et al. Multicenter trial of sentinel node biopsy for breast cancer using both technetium sulfur colloid and isosulfan blue dye. Ann Surg. 2001; 233:51–9.

26. Woo CS, Silberman H, Nakamura SK, Ye W, Sposto R, Colburn W, et al. Lymph node status combined with lymphovascular invasion creates a more powerful tool for predicting outcome in patients with invasive breast cancer. Am J Surg. 2002; 184:337–40.

27. Rivers AK, Griffith KA, Hunt KK, Degnim AC, Sabel MS, Diehl KM, et al. Clinicopathologic features associated with having four or more metastatic axillary nodes in breast cancer patients with a positive sentinel lymph node. Ann Surg Oncol. 2006; 13:36–44.

28. Gill J, Lovegrove R, Naessens K, Pursell R, Cominos T, McCormick C, et al. Sentinel lymph node biopsy in breast cancer: an analysis of the maximum number of nodes requiring excision. Breast J. 2011; 17:3–8.

29. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005; 365:1687–717.