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Clinical significance of breast cancer micrometastasis in the sentinel lymph node

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Abstract

The advantages of sentinel lymph node biopsy (SLNB) in breast cancer patients include an enhanced pathological examination of a small number of sentinel lymph nodes (SLNs), which permits more frequent detection of micrometastasis and isolated tumor cells (ITCs). At the same time, however, SLNB raises two new concerns: whether minimal SLN involvement has a significant impact on survival and whether patients with such minimal involvement should undergo further axillary dissections. Two large randomized studies, ACOSOG Z0011 and IBCSG 23-01, have demonstrated that axillary lymph node dissection (ALND) can be avoided for select SLN-positive patients. However, for patients with macrometastasis in SLN or who do not meet the inclusion criteria of the two studies, ALND is still the standard management. On the other hand, previous studies appear to disagree on the prognostic significance of minimal SLN involvement. One of the reasons for this discrepancy is the great variability among pathological examinations for SLN. The OSNA method, which is a fast molecular detection procedure targeting cytokeratin 19 (CK19) mRNA, has the advantage of reproducibility among institutions and the capability to examine a whole lymph node within 30–40 min. This novel method may thus be able to overcome the issue of variability among conventional pathological examinations.

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References

  1. Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220:391–8 (Discussion 398–401).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Shimazu K, Tamaki Y, Taguchi T, Takamura Y, Noguchi S. Comparison between periareolar and peritumoral injection of radiotracer for sentinel lymph node biopsy in patients with breast cancer. Surgery. 2002;131:277–86.

    Article  PubMed  Google Scholar 

  3. Shimazu K, Tamaki Y, Taguchi T, Motomura K, Inaji H, Koyama H, et al. Lymphoscintigraphic visualization of internal mammary nodes with subtumoral injection of radiocolloid in patients with breast cancer. Ann Surg. 2003;237:390–8.

    PubMed Central  PubMed  Google Scholar 

  4. Miyake T, Shimazu K, Ohashi H, Taguchi T, Ueda S, Nakayama T, et al. Indication for sentinel lymph node biopsy for breast cancer when core biopsy shows ductal carcinoma in situ. Am J Surg. 2011;202:59–65.

    Article  PubMed  Google Scholar 

  5. Shimazu K, Tamaki Y, Taguchi T, Akazawa K, Inoue T, Noguchi S. Sentinel lymph node biopsy using periareolar injection of radiocolloid for patients with neoadjuvant chemotherapy-treated breast carcinoma. Cancer. 2004;100:2555–61.

    Article  PubMed  Google Scholar 

  6. Ogawa Y, Ikeda K, Ogisawa K, Tokunaga S, Fukushima H, Inoue T, et al. Outcome of sentinel lymph node biopsy in breast cancer using dye alone: a single center review with a median follow-up of 5 years. Surg Today. 2014;44(9):1633–7.

    Article  PubMed  Google Scholar 

  7. Ikeda T. Re-sentinel node biopsy after previous breast and axillary surgery. Surg Today. 2014;44(11):2015–21.

    Article  PubMed  Google Scholar 

  8. Tanaka S, Sato N, Fujioka H, Takahashi Y, Kimura K, Iwamoto M. 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):163–70.

    Article  PubMed  Google Scholar 

  9. Imasato M, Shimazu K, Tamaki Y, Taguchi T, Tanji Y, Kim SJ, et al. Long-term follow-up results of breast cancer patients with sentinel lymph node biopsy using periareolar injection. Am J Surg. 2010;199:442–6.

    Article  PubMed  Google Scholar 

  10. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  11. 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.

    Article  PubMed  Google Scholar 

  12. Hansen NM, Grube B, Ye X, Turner RR, Brenner RJ, Sim MS, et al. Impact of micrometastases in the sentinel node of patients with invasive breast cancer. J Clin Oncol. 2009;27:4679–84.

    Article  PubMed  Google Scholar 

  13. Gobardhan PD, Elias SG, Madsen EV, van Wely B, van den Wildenberg F, Theunissen EB, et al. Prognostic value of lymph node micrometastases in breast cancer: a multicenter cohort study. Ann Surg Oncol. 2011;18:1657–64.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Maaskant-Braat AJ, van de Poll-Franse LV, Voogd AC, Coebergh JW, Roumen RM, Nolthenius-Puylaert MC, et al. Sentinel node micrometastases in breast cancer do not affect prognosis: a population-based study. Breast Cancer Res Treat. 2011;127:195–203.

    Article  PubMed  Google Scholar 

  15. de Boer M, van Deurzen CH, van Dijck JA, Borm GF, van Diest PJ, Adang EM, et al. Micrometastases or isolated tumor cells and the outcome of breast cancer. N Engl J Med. 2009;361:653–63.

    Article  PubMed  Google Scholar 

  16. Andersson Y, Frisell J, Sylvan M, de Boniface J, Bergkvist L. Breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes. J Clin Oncol. 2010;28:2868–73.

    Article  PubMed  Google Scholar 

  17. Weaver DL, Ashikaga T, Krag DN, Skelly JM, Anderson SJ, Harlow SP, et al. Effect of occult metastases on survival in node-negative breast cancer. N Engl J Med. 2011;364:412–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Saphner T, Tormey DC, Gray R. Annual hazard rates of recurrence for breast cancer after primary therapy. J Clin Oncol. 1996;14:2738–46.

    CAS  PubMed  Google Scholar 

  19. Bilimoria KY, Bentrem DJ, Hansen NM, Bethke KP, Rademaker AW, Ko CY, et al. Comparison of sentinel lymph node biopsy alone and completion axillary lymph node dissection for node-positive breast cancer. J Clin Oncol. 2009;27:2946–53.

    Article  PubMed  Google Scholar 

  20. Yi M, Giordano SH, Meric-Bernstam F, Mittendorf EA, Kuerer HM, Hwang RF, et al. Trends in and outcomes from sentinel lymph node biopsy (SLNB) alone vs. SLNB with axillary lymph node dissection for node-positive breast cancer patients: experience from the SEER database. Ann Surg Oncol. 2010;17(Suppl 3):343–51.

    Article  PubMed Central  PubMed  Google Scholar 

  21. 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;255:116–21.

    Article  PubMed  Google Scholar 

  22. 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;305:569–75.

    Article  CAS  PubMed  Google Scholar 

  23. Galimberti V, Cole BF, Zurrida S, Viale G, Luini A, Veronesi P, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol. 2013;14:297–305.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Morcos B, Ahmad FA, Anabtawi I, Sba’ AM, Shabani H, Yaseen R. Development of breast cancer-related lymphedema: is it dependent on the patient, the tumor or the treating physicians? Surg Today. 2014;44(1):100–6.

    Article  PubMed  Google Scholar 

  25. Budach W, Kammers K, Boelke E, Matuschek C. Adjuvant radiotherapy of regional lymph nodes in breast cancer—a meta-analysis of randomized trials. Radiat Oncol. 2013;8:267–73.

    Article  PubMed Central  PubMed  Google Scholar 

  26. EBCTCG (Early Breast Cancer Trialists’ Collaborative Group), McGale P, Taylor C, Correa C, Cutter D, Duane F, Ewertz M, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383:2127–35.

    Article  Google Scholar 

  27. Park D, Kåresen R, Naume B, Synnestvedt M, Beraki E, Sauer T. The prognostic impact of occult nodal metastasis in early breast carcinoma. Breast Cancer Res Treat. 2009;118:57–66.

    Article  PubMed  Google Scholar 

  28. Viale G, Bosari S, Mazzarol G, Galimberti V, Luini A, Veronesi P, et al. Intraoperative examination of axillary sentinel lymph nodes in breast carcinoma patients. Cancer. 1999;85:2433–8.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Article  CAS  PubMed  Google Scholar 

  30. Tamaki Y, Akiyama F, Iwase T, Kaneko T, Tsuda H, Sato K, 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.

    Article  CAS  PubMed  Google Scholar 

  31. Tamaki Y, Sato N, Homma K, Takabatake D, Nishimura R, Tsujimoto M, et al. Routine clinical use of the one-step nucleic acid amplification assay for detection of sentinel lymph node metastases in breast cancer patients: results of a multicenter study in Japan. Cancer. 2012;118:3477–83.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. 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.

    Article  PubMed  Google Scholar 

  34. Feldman S, Krishnamurthy S, Gillanders W, Gittelman M, Beitsch PD, Young PR, et al. A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes. Cancer. 2011;117:2599–607.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. 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.

    PubMed  Google Scholar 

  36. Snook KL, Layer GT, Jackson PA, de Vries CS, Shousha S, Sinnett HD, et al. Multicentre evaluation of intraoperative molecular analysis of sentinel lymph nodes in breast carcinoma. Br J Surg. 2011;98:527–35.

    Article  CAS  PubMed  Google Scholar 

  37. Le Fre`re-Belda MA, Bats AS, Gillaizeau F, Poulet B, Clough KB, Nos C, et al. Diagnostic performance of one-step nucleic acid amplification for intraoperative sentinel node metastasis detection in breast cancer patients. Int J Cancer. 2011;130:2377–86.

    Article  Google Scholar 

  38. Bernet L, Cano R, Martinez M, Duen˜as B, Matias-Guiu X, Morell L, et al. Diagnosis of the sentinel lymph node in breast cancer: a reproducible molecular method: a multicentric Spanish study. Histopathology. 2011;58:863–9.

    Article  PubMed  Google Scholar 

  39. Sagara Y, Ohi Y, Matsukata A, Yotsumoto D, Baba S, Tamada S, et al. Clinical application of the one-step nucleic acid amplification method to detect sentinel lymph node metastasis in breast cancer. Breast Cancer. 2013;20:181–6.

    Article  PubMed  Google Scholar 

  40. Wang YS, Ou-yang T, Wu J, Liu YH, Cao XC, Sun X, et al. Comparative study of one-step nucleic acid amplification assay, frozen section, and touch imprint cytology for intraoperative assessment of breast sentinel lymph node in Chinese patients. Cancer Sci. 2012;103:1989–93.

    Article  CAS  PubMed  Google Scholar 

  41. Osako T, Iwase T, Kimura K, Horii R, Akiyama F. Sentinel node tumour burden quantified based on cytokeratin 19 mRNA copy number predicts non-sentinel node metastases in breast cancer: molecular whole-node analysis of all removed nodes. Eur J Cancer. 2013;49:1187–95.

    Article  CAS  PubMed  Google Scholar 

  42. Peg V, Espinosa-Bravo M, Vieites B, Vilardell F, Antúnez JR, de Salas MS, et al. 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. 2013;139:87–93.

    Article  CAS  PubMed  Google Scholar 

  43. Teramoto A, Shimazu K, Naoi Y, Shimomura A, Shimoda M, Kagara N, et al. One-step nucleic acid amplification assay for intraoperative prediction of non-sentinel lymph node metastasis in breast cancer patients with sentinel lymph node metastasis. Breast. 2014;23:579–85.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Kenzo Shimazu & Shinzaburo Noguchi

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  1. Kenzo Shimazu
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  2. Shinzaburo Noguchi
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Correspondence to Shinzaburo Noguchi.

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Shimazu, K., Noguchi, S. Clinical significance of breast cancer micrometastasis in the sentinel lymph node. Surg Today 46, 155–160 (2016). https://doi.org/10.1007/s00595-015-1168-5

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