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The prognostic impact of occult nodal metastasis in early breast carcinoma

  • Daehoon ParkEmail author
  • Rolf Kåresen
  • Bjørn Naume
  • Marit Synnestvedt
  • Elsa Beraki
  • Torill Sauer
Cinical Trial

Abstract

The clinical relevance of isolated tumor cell (ITC: ≤0.2 mm) and micrometastasis (MM: >0.2–2.0 mm) in axillary lymph nodes (ALNs) remains unknown. The aim of this study was to determine their prognostic significance. A total of 295 patients considered as pN0 after routine histological assessment, were reevaluated with ten-level cytokeratin immunohistochemistry (IHC) and two-level hematoxylin-eosin sections. Survival rates, i.e. disease-free survival (DFS), distant disease-free survival (DDFS) and breast cancer specific survival (BCSS) were compared with those of reevaluated node-negative patients. A total of 84 patients (28%) had ITC/MM identified on IHC sections. ITC had no impact on survival at a median 8.2 years of follow-up, whereas MM showed a trend toward poorer DFS (P = 0.091, log rank) and DDFS (P = 0.066) and significantly reduced BCSS (P = 0.016). In multivariate analyses, detection of MM was an independent prognostic factor for DDFS (P = 0.025) and BCSS (P = 0.01) in adjuvant un-treated patients. Micrometastases (MMs) in axillary lymph nodes have prognostic impact. This was not found for ITC. This finding supports the use of systemic adjuvant therapy in patients with MM.

Keywords

Occult metastasis Axillary lymph node Invasive breast cancer Survival Prognosis 

References

  1. 1.
    Lacroix M (2006) Significance, detection and markers of disseminated breast cancer cells. Endocr Relat Cancer 13:1033–1067. doi: 10.1677/ERC-06-0001 CrossRefPubMedGoogle Scholar
  2. 2.
    Swenson KK, Nissen MJ, Ceronsky C et al (2002) Comparison of side effects between sentinel lymph node and axillary lymph node dissection for breast cancer. Ann Surg Oncol 9:745–753CrossRefPubMedGoogle Scholar
  3. 3.
    Blanchard DK, Donohue JH, Reynolds C, Grant CS (2003) Relapse and morbidity in patients undergoing sentinel lymph node biopsy alone or with axillary dissection for breast cancer. Arch Surg 138:482–488. doi: 10.1001/archsurg.138.5.482 CrossRefPubMedGoogle Scholar
  4. 4.
    Greene FL, Page DL, Fleming ID et al (2002) American Joint Committee on cancer staging manual, 6th edn. Springer, New YorkGoogle Scholar
  5. 5.
    Dowlatshahi K, Fan M, Snider HC, Habib FA (1997) Lymph node micrometastases from breast carcinoma: reviewing the dilemma. Cancer 80:1188–1197. doi: 10.1002/(SICI)1097-0142(19971001)80:7<1188::AID-CNCR2>3.0.CO;2-H CrossRefPubMedGoogle Scholar
  6. 6.
    Hawes D, Neville AM, Cote RJ (2001) Detection of occult metastasis in patients with breast cancer. Semin Surg Oncol 20:312–318. doi: 10.1002/ssu.1049 CrossRefPubMedGoogle Scholar
  7. 7.
    Chagpar A, Middleton LP, Sahin AA et al (2005) Clinical outcome of patients with lymph node-negative breast carcinoma who have sentinel lymph node micrometastases detected by immunohistochemistry. Cancer 103:1581–1586. doi: 10.1002/cncr.20934 CrossRefPubMedGoogle Scholar
  8. 8.
    Cox CE, Kiluk JV, Riker AI et al (2008) Significance of sentinel lymph node micrometastases in human breast cancer. J Am Coll Surg 206:261–268. doi: 10.1016/j.jamcollsurg.2007.08.024 CrossRefPubMedGoogle Scholar
  9. 9.
    Cummings MC, Walsh MD, Hohn BG et al (2002) Occult axillary lymph node metastases in breast cancer do matter: results of 10-year survival analysis. Am J Surg Pathol 26:1286–1295. doi: 10.1097/00000478-200210000-00005 CrossRefPubMedGoogle Scholar
  10. 10.
    Herbert GS, Sohn VY, Brown TA (2007) The impact of nodal isolated tumor cells on survival of breast cancer patients. Am J Surg 193:571–574. doi: 10.1016/j.amjsurg.2007.01.007 CrossRefPubMedGoogle Scholar
  11. 11.
    Kahn HJ, Hanna WM, Chapman JA et al (2006) Biological significance of occult micrometastases in histologically negative axillary lymph nodes in breast cancer patients using the recent American Joint Committee on Cancer breast cancer staging system. Breast J 12:294–301. doi: 10.1111/j.1075-122X.2006.00267.x CrossRefPubMedGoogle Scholar
  12. 12.
    Millis RR, Springall R, Lee AH et al (2002) Occult axillary lymph node metastases are of no prognostic significance in breast cancer. Br J Cancer 86:396–401. doi: 10.1038/sj.bjc.6600070 CrossRefPubMedGoogle Scholar
  13. 13.
    Susnik B, Frkovic-Grazio S, Bracko M (2004) Occult micrometastases in axillary lymph nodes predict subsequent distant metastases in stage I breast cancer: a case-control study with 15-year follow-up. Ann Surg Oncol 11:568–572. doi: 10.1245/ASO.2004.10.021 CrossRefPubMedGoogle Scholar
  14. 14.
    Tan LK, Giri D, Hummer AJ et al (2008) Occult axillary node metastases in breast cancer are prognostically significant: results in 368 node-negative patients with 20-year follow-up. J Clin Oncol 26:1803–1809. doi: 10.1200/JCO.2007.12.6425 CrossRefPubMedGoogle Scholar
  15. 15.
    Fisher B, Bauer M, Wickerham DL et al (1983) Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer 52:1551–1557. doi: 10.1002/1097-0142(19831101)52:9<1551::AID-CNCR2820520902>3.0.CO;2-3 CrossRefPubMedGoogle Scholar
  16. 16.
    Rosen PP, Saigo PE, Braun DW Jr et al (1981) Predictors of recurrence in stage I (T1N0M0) breast carcinoma. Ann Surg 193:15–25. doi: 10.1097/00000658-198101000-00003 CrossRefPubMedGoogle Scholar
  17. 17.
    Braun S, Cevatli BS, Assemi C et al (2001) Comparative analysis of micrometastasis to the bone marrow and lymph nodes of node-negative breast cancer patients receiving no adjuvant therapy. J Clin Oncol 19:1468–1475PubMedGoogle Scholar
  18. 18.
    Wiedswang G, Naess AB, Naume B, Karesen R (2001) Micrometastasis to axillary lymph nodes and bone marrow in breast cancer patients. Breast 10:237–242. doi: 10.1054/brst.2000.0245 CrossRefPubMedGoogle Scholar
  19. 19.
    Gerber B, Krause A, Muller H et al (2001) Simultaneous immunohistochemical detection of tumor cells in lymph nodes and bone marrow aspirates in breast cancer and its correlation with other prognostic factors. J Clin Oncol 19:960–971PubMedGoogle Scholar
  20. 20.
    Naume B, Borgen E, Kvalheim G et al (2001) Detection of isolated tumor cells in bone marrow in early-stage breast carcinoma patients: comparison with preoperative clinical parameters and primary tumor characteristics. Clin Cancer Res 7:4122–4129PubMedGoogle Scholar
  21. 21.
    Wiedswang G, Borgen E, Karesen R et al (2003) Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 21:3469–3478. doi: 10.1200/JCO.2003.02.009 CrossRefPubMedGoogle Scholar
  22. 22.
    Brystkreft. Diagnostikk og behandling. Norwegian Breast Cancer Group. 4th Edition 1994 and 5th Edition 1998 (in Norwegian)Google Scholar
  23. 23.
    Hainsworth PJ, Tjandra JJ, Stillwell RG et al (1993) Detection and significance of occult metastases in node-negative breast cancer. Br J Surg 80:459–463. doi: 10.1002/bjs.1800800417 CrossRefPubMedGoogle Scholar
  24. 24.
    Trojani M, de Mascarel I, Bonichon F et al (1987) Micrometastases to axillary lymph nodes from carcinoma of breast: detection by immunohistochemistry and prognostic significance. Br J Cancer 55:303–306PubMedGoogle Scholar
  25. 25.
    International (Ludwig) Breast Cancer Study Group (1990) Prognostic importance of occult axillary lymph node micrometastases from breast cancers. Lancet 335:1565–1568Google Scholar
  26. 26.
    de Mascarel I, Bonichon F, Coindre JM, Trojani M (1992) Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow-up. Br J Cancer 66:523–527PubMedGoogle Scholar
  27. 27.
    Madsen EV, van Dalen J, van Gorp J et al (2008) Strategies for optimizing pathologic staging of sentinel lymph nodes in breast cancer patients. Virchows Arch 453:17–24. doi: 10.1007/s00428-008-0601-1 CrossRefPubMedGoogle Scholar
  28. 28.
    Park D, Karesen R, Axcrona U et al (2007) Expression pattern of adhesion molecules (E-cadherin, alpha-, beta-, gamma-catenin and claudin-7), their influence on survival in primary breast carcinoma, and their corresponding axillary lymph node metastasis. APMIS 115:52–65. doi: 10.1111/j.1600-0463.2007.apm_524.x CrossRefPubMedGoogle Scholar
  29. 29.
    Langer I, Guller U, Koechli OR et al (2007) Association of the presence of bone marrow micrometastases with the sentinel lymph node status in 410 early stage breast cancer patients: results of the Swiss Multicenter Study. Ann Surg Oncol 14:1896–1903. doi: 10.1245/s10434-006-9193-7 CrossRefPubMedGoogle Scholar
  30. 30.
    Carter BA, Jensen RA, Simpson JF, Page DL (2000) Benign transport of breast epithelium into axillary lymph nodes after biopsy. Am J Clin Pathol 113:259–265. doi: 10.1309/7EF8-F1W7-YVNT-H8H5 CrossRefPubMedGoogle Scholar
  31. 31.
    Naik AM, Fey J, Gemignani M et al (2004) The risk of axillary relapse after sentinel lymph node biopsy for breast cancer is comparable with that of axillary lymph node dissection: a follow-up study of 4008 procedures. Ann Surg 240:462–468. doi: 10.1097/01.sla.0000137130.23530.19 CrossRefPubMedGoogle Scholar
  32. 32.
    Fisher B, Anderson S, Bryant J et al (2002) 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 347:1233–1241. doi: 10.1056/NEJMoa022152 CrossRefPubMedGoogle Scholar
  33. 33.
    Kuijt GP, van de Poll-Franse LV, Roumen RM et al (2006) The significance of one positive axillary node. Eur J Surg Oncol 32:139–142. doi: 10.1016/j.ejso.2005.11.015 CrossRefPubMedGoogle Scholar
  34. 34.
    Viale G, Maiorano E, Pruneri G et al (2005) Predicting the risk for additional axillary metastases in patients with breast carcinoma and positive sentinel lymph node biopsy. Ann Surg 241:319–325. doi: 10.1097/01.sla.0000150255.30665.52 CrossRefPubMedGoogle Scholar
  35. 35.
    Rutgers EJ, Meijnen P, Bonnefoi H (2004) Clinical trials update of the European Organization for Research and Treatment of Cancer Breast Cancer Group. Breast Cancer Res 6:165–169. doi: 10.1186/bcr906 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Daehoon Park
    • 1
    Email author
  • Rolf Kåresen
    • 2
  • Bjørn Naume
    • 3
  • Marit Synnestvedt
    • 3
  • Elsa Beraki
    • 1
  • Torill Sauer
    • 1
  1. 1.Department of Pathology, Oslo University HospitalUniversity of OsloOsloNorway
  2. 2.Department of Surgery, Oslo University HospitalUniversity of OsloOsloNorway
  3. 3.Department of Oncology, Oslo University HospitalThe Norwegian Radium HospitalOsloNorway

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