Nomogram to predict non-sentinel lymph node status using total tumor load determined by one-step nucleic acid amplification: first report from Thailand
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Axillary staging is a significant prognostic factor often used to determine the treatment course for breast cancer. One-step nucleic acid amplification (OSNA) is now the most accepted method for intra-operative assessment of sentinel lymph nodes (SLN) as it can semi-quantitatively determine the tumor burden in these SLN. Axillary lymph node dissection (ALND) may be omitted in patients with limited disease in the axilla. The objective was to create nomogram for prediction of non-sentinel lymph node (NSLN) status using OSNA to avoid unnecessary ALND.
Patients and methods
Patients with invasive breast cancer T1–T3 and clinically negative axillary lymph nodes underwent SLN biopsy assessed by OSNA. The patients with positive SLN underwent ALND. Correlations between total tumor load (TTL), clinicopathological parameters, and NSLN status were analyzed by Chi square statistic and logistic regression. Model discrimination was evaluated using receiver-operating characteristic (ROC) analysis.
The total number of patients who underwent SLN biopsies was 278. There were 89 patients with positive SLN. NSLNs were positive in 40 patients. Larger tumor size, presence of lymphovascular invasion (LVI) and higher log TTL were independent factors that predicted positive NSLN. TTL can discriminate NSLN status with area under the ROC curve of 0.789 (95% CI 0.686–0.892). Two nomograms using different parameters obtained pre- and post-operatively can predict NSLN involvement with better area under the ROC curve (0.801, 95% CI 0.702–0.900 and 0.849, 95% CI 0.766–0.932, respectively).
Nomograms using results obtained via OSNA can predict NSLN status, as well as aid in deciding to omit the use of ALND.
KeywordsBreast cancer Sentinel lymph node One-step nucleic acid amplification Nomogram
This study was supported by Siriraj Research and Development Fund and Sysmex Asia-Pacific Pte Ltd.
Siriraj Research and Development Fund. Sysmex Asia-Pacific Pte Ltd.
Compliance with ethical standards
Conflict of interest
The authors declared no conflict of interest. Sysmex Asia-Pacific Pte Ltd. had no influence in the analysis and interpretation of the results.
- 2.Mohammed ZM, McMillan DC, Edwards J, Mallon E, Doughty JC, Orange C, et al. The relationship between lymphovascular invasion and angiogenesis, hormone receptors, cell proliferation and survival in patients with primary operable invasive ductal breast cancer. BMC Clin Pathol. 2013;13:31.CrossRefGoogle Scholar
- 3.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.CrossRefGoogle Scholar
- 7.Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15:1303–10.CrossRefGoogle Scholar
- 8.Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918–26.CrossRefGoogle Scholar
- 15.Chaudhry A, Williams S, Cook J, Jenkins M, Sohail M, Calder C, et al. The real-time intra-operative evaluation of sentinel lymph nodes in breast cancer patients using one step nucleic acid amplification (OSNA) and implications for clinical decision-making. Eur J Surg Oncol. 2014;40:150–7.CrossRefGoogle Scholar
- 16.Deambrogio C, Castellano I, Paganotti A, Zorini EO, Corsi F, Bussone R, et al. A new clinical cut-off of cytokeratin 19 mRNA copy number in sentinel lymph node better identifies patients eligible for axillary lymph node dissection in breast cancer. J Clin Pathol. 2014;67:702–6.CrossRefGoogle Scholar
- 17.Heilmann T, Mathiak M, Hofmann J, Mundhenke C, van Mackelenbergh M, Alkatout I, et al. Intra-operative use of one-step nucleic acid amplification (OSNA) for detection of the tumor load of sentinel lymph nodes in breast cancer patients. J Cancer Res Clin Oncol. 2013;139:1649–55.CrossRefGoogle Scholar
- 20.Rubio IT, Espinosa-Bravo M, Rodrigo M, Amparo Viguri Diaz M, Hardisson D, Sagasta A, 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. 2014;147:371–80.CrossRefGoogle Scholar
- 21.Shimazu K, Sato N, Ogiya A, Sota Y, Yotsumoto D, Ishikawa T, et al. Intraoperative nomograms, based on one-step nucleic acid amplification, for prediction of non-sentinel node metastasis and four or more axillary node metastases in breast cancer patients with sentinel node metastasis. Ann Surg Oncol. 2018;25:2603–11.CrossRefGoogle Scholar
- 22.Khaddage A, Berremila SA, Forest F, Clemenson A, Bouteille C, Seffert P, et al. Implementation of molecular intra-operative assessment of sentinel lymph node in breast cancer. Anticancer Res. 2011;31:585–90.Google Scholar
- 23.Osako T, Iwase T, Kimura K, Yamashita K, Horii R, Yanagisawa A, et al. Intraoperative molecular assay for sentinel lymph node metastases in early stage breast cancer: a comparative analysis between one-step nucleic acid amplification whole node assay and routine frozen section histology. Cancer. 2011;117:4365–74.CrossRefGoogle Scholar
- 28.Kubota M, Komoike Y, Hamada M, Shinzaki W, Azumi T, Hashimoto Y, et al. One-step nucleic acid amplification assay for intraoperative prediction of advanced axillary lymph node metastases in breast cancer patients with sentinel lymph node metastasis. Mol Clin Oncol. 2016;4:173–8.CrossRefGoogle Scholar
- 30.Christine K, Reilly S, Charles M, Martin R, Sanford R, Thomas S, et al. Significant discordance of lymphovascular invasion between breast cancer core biopsies and surgical specimens limits its role as a tool for preoperative prediction of nodal metastasis. In: The American society of breast surgeons 18th Annual Meeting April 26–30, 2017, Las Vegas, NV. 2017. Available at: https://www.breastsurgeons.org/docs2017/posters/ASBrS_2017_Poster_256753.pdf. Accessed 25 Dec 2018.