Annals of Surgical Oncology

, Volume 13, Issue 4, pp 465–474 | Cite as

The Prognostic Effect of the Number of Histologically Examined Axillary Lymph Nodes in Breast Cancer: Stage Migration or Age Association?

  • Michael Schaapveld
  • Elisabeth G. E. de Vries
  • Winette T. A. van der Graaf
  • Renée Otter
  • Jakob de Vries
  • Pax H. B. Willemse



The number of pathologically examined axillary nodes has been associated with breast cancer survival, and examination of ≥10 nodes has been advocated for reliable axillary staging. The considerable variation observed in axillary staging prompted this population-based study, which evaluated the prognostic effect of a variable number of pathologically examined nodes.


In total, 5314 consecutive breast cancer patients who underwent mastectomy or breast-conserving surgery and axillary dissection between 1994 and 1999 were included. The prognostic effect of the examined number of nodes was assessed with crude and relative survival analysis.


A median number of 12 (range, 1–43) nodes were histologically examined, and 59% of the patients had no nodal tumor involvement. The number of examined nodes decreased with age (P < .001) and increased with tumor size (P < .001). Stratified for the number of tumor-positive nodes, overall survival seemed to be worse for patients with <10 compared with patients with ≥10 examined nodes (P < .001), whereas the relative survival did not differ. After adjusting for age, tumor size, number of positive nodes, and detection by screening in a multivariate analysis, the number of examined nodes was not associated with relative survival.


This study shows that the association between the number of pathologically examined axillary nodes and overall survival in node-negative and node-positive patients results from stage migration. The absence of an association between the number of examined nodes and relative survival further indicates that the association between the number of examined nodes and crude survival is confounded by age.


Breast cancer Axillary staging Crude survival Relative survival Prognosis 


  1. 1.
    National Comprehensive Cancer Network: update of the NCCN guidelines for treatment of breast cancer. Oncology 1997;11:199–222Google Scholar
  2. 2.
    Link BK, Budd GT, Scott S, et al. Oncology Practice Pattern Study Working Group. Delivering adjuvant chemotherapy to women with early-stage breast carcinoma. Current patterns of care. Cancer 2001;92:1354–67PubMedGoogle Scholar
  3. 3.
    Olivotto IA, Jackson JS, Mates D, et al. Prediction of axillary lymph node involvement of women with invasive breast carcinoma: a multivariate analysis. Cancer 1998;83:948–55CrossRefPubMedGoogle Scholar
  4. 4.
    Voogd AC, Coebergh JW, Repelaer van Driel OJ, et al. The risk of nodal metastases in breast cancer patients with clinically negative lymph nodes: a population-based analysis. Breast Cancer Res Treat 2000;62:63–9CrossRefPubMedGoogle Scholar
  5. 5.
    Veronesi U, Paganelli G, Galimberti V, et al. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet 1997;349:1864–7CrossRefPubMedGoogle Scholar
  6. 6.
    McMasters KM, Giuliano AE, Ross MI, et al. Sentinel-lymph-node biopsy for breast cancer—not yet the standard of care. N Engl J Med 1998;339:990–5CrossRefPubMedGoogle Scholar
  7. 7.
    Reynolds C, Mick R, Donohue JH, et al. Sentinel lymph node biopsy with metastasis: can axillary dissection be avoided in some patients with breast cancer? J Clin Oncol 1999;17:1720–6PubMedGoogle Scholar
  8. 8.
    Giuliano AE, Haigh PI, Brennan MB, et al. Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer. J Clin Oncol 2000;18:2553–9PubMedGoogle Scholar
  9. 9.
    Krag D, Ashikaga T, Abrams J. Sentinel nodes: clinical trial data needed. J Clin Oncol 2000;18:3873–4PubMedGoogle Scholar
  10. 10.
    Edge SB, Niland JC, Bookman MA, et al. Emergence of sentinel node biopsy in breast cancer as standard-of-care in academic comprehensive cancer centers. J Natl Cancer Inst 2003;95:1514–21PubMedGoogle Scholar
  11. 11.
    Fisher B, Wolmark N, Bauer M, Redmond C, Gebhardt M. The accuracy of clinical nodal staging and of limited axillary dissection as a determinant of histologic nodal status in carcinoma of the breast. Surg Gynecol Obstet 1981;152:765–22PubMedGoogle Scholar
  12. 12.
    Rosen PP, Lesser ML, Kinne DW, Beattie EJ. Discontinuous or “skip” metastases in breast carcinoma: analysis of 1228 axillary dissections. Ann Surg 1983;4:655–62Google Scholar
  13. 13.
    Schaapveld M, Otter R, de Vries EG, et al. Variability in axillary lymph node dissection for breast cancer. J Surg Oncol 2004;87:4–12CrossRefPubMedGoogle Scholar
  14. 14.
    Wilking N, Rutqvist LE, Carstensen J, Mattsson A, Skoog L. Prognostic significance of axillary nodal status in primary breast cancer in relation to the number of resected nodes. Acta Oncol 1992;31:29–35PubMedGoogle Scholar
  15. 15.
    Fisher B, Slack NH. Number of lymph nodes examined and the prognosis of breast carcinoma. Surg Gynecol Obstet 1970;131:79–88PubMedGoogle Scholar
  16. 16.
    Kjaergaard J, Blichert-Toft M, Andersen JA, Rank F, Pedersen BV. Probability of false negative nodal staging in conjunction with partial axillary dissection in breast cancer. Br J Surg 1985;72:365–7PubMedGoogle Scholar
  17. 17.
    Jatoi I, Hilsenbeck SG, Clarck GM, Osborne CK. Significance of axillary lymph nodes metastasis in primary breast cancer. J Clin Oncol 1999;17:2334–40PubMedGoogle Scholar
  18. 18.
    Camp RL, Rimm EB, Rimm DL. A high number of tumor free axillary lymph nodes from patients with lymph node negative breast carcinoma is associated with poor outcome. Cancer 2000;88:108–13CrossRefPubMedGoogle Scholar
  19. 19.
    Moorman PG, Hamza A, Marks JR, Olson JA. Prognostic significance of the number of lymph nodes examined in patients with lymph node-negative breast carcinoma. Cancer 2001;91:2258–62CrossRefPubMedGoogle Scholar
  20. 20.
    Weir L, Speers C, D’yachkova Y, Olivotto IA. Prognostic significance of the number of axillary lymph nodes removed in patients with node negative breast cancer. J Clin Oncol 2002;20:1793–9CrossRefPubMedGoogle Scholar
  21. 21.
    Krag DN, Single RM. Breast cancer survival according to number of nodes removed. Ann Surg Oncol 2003;10:1152–9CrossRefPubMedGoogle Scholar
  22. 22.
    Polednak AP. Survival of lymph node-negative breast cancer in relation to number of lymph nodes examined. Ann Surg 2003;237:163–7CrossRefPubMedGoogle Scholar
  23. 23.
    Du X, Freeman JL, Goodwin JS. The declining use of axillary dissection in patients with early stage breast cancer. Breast Cancer Res Treat 1999;53:137–44CrossRefPubMedGoogle Scholar
  24. 24.
    Hermanek P, Sobin LH (eds). International Union Against Cancer (UICC): TNM Classification of Malignant Tumors. 4th ed, 2nd rev. Berlin: Springer-Verlag, 1992Google Scholar
  25. 25.
    Sobin LH, Wittekind C (eds). International Union Against Cancer (UICC): TNM Classification of Malignant Tumors. 5th ed. New York: Wiley-Liss, 1997Google Scholar
  26. 26.
    Statistics Netherlands/Centraal Bureau voor de Statistiek. Available at: [accessed February 2, 2006]
  27. 27.
    Ederer F, Heise H. Instructions to IBM 650 Programmers in Processing Survival Computations. Methodological Note No. 10, End Results Evaluation Section. Bethesda, MD: National Cancer Institute, 1959Google Scholar
  28. 28.
    Dickman PW, Sloggett A, Hills M, Hakulinen T. Regression models for relative survival and the estimation of net survival. Stat Med 2004;23:51–64CrossRefPubMedGoogle Scholar
  29. 29.
    McCullagh P, Nelder JA. Generalized Linear Models. 2nd ed. London: Chapman & Hall, 1989Google Scholar
  30. 30.
    Feinstein AR, Sosin DM, Wells CK. The Will Rogers phenomenon: stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. N Engl J Med 1985;312:1604–8PubMedGoogle Scholar
  31. 31.
    Orr RK. The impact of prophylactic axillary node dissection on breast cancer survival—a Bayesian meta-analysis. Ann Surg Oncol 1999;6:109–16CrossRefPubMedGoogle Scholar
  32. 32.
    Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 1998;351:1451–67Google Scholar
  33. 33.
    Early Breast Cancer Trialists’ Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 1998;352:930–45Google Scholar
  34. 34.
    Whelan TJ, Julian J, Wright J, Jadad AR, Levine ML. Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis. J Clin Oncol 2000;18:1220–9.PubMedGoogle Scholar
  35. 35.
    Haffty BG, Lee C, Philpotts L, et al. Prognostic significance of mammographic detection in a cohort of conservatively treated breast cancer patients. Cancer J Sci Am 1998;4:35–40PubMedGoogle Scholar
  36. 36.
    Gill PG, Farshid G, Luke CG, Roder DM. Detection by screening mammography is a powerful independent predictor of survival in women diagnosed with breast cancer. Breast 2004;13:15–22CrossRefPubMedGoogle Scholar
  37. 37.
    Ernst MF, Voogd AC, Coebergh JW, Roukema JA. Breast carcinoma diagnosis, treatment, and prognosis before and after the introduction of mass mammographic screening. Cancer 2004;100:1337–44CrossRefPubMedGoogle Scholar

Copyright information

© The Society of Surgical Oncology, Inc. 2006

Authors and Affiliations

  • Michael Schaapveld
    • 1
  • Elisabeth G. E. de Vries
    • 2
  • Winette T. A. van der Graaf
    • 2
  • Renée Otter
    • 1
  • Jakob de Vries
    • 3
  • Pax H. B. Willemse
    • 2
  1. 1.Comprehensive Cancer Center North-NetherlandsThe Netherlands
  2. 2.Department of Medical OncologyUniversity Medical Center GroningenThe Netherlands
  3. 3.Department of Surgical OncologyUniversity Medical Center GroningenThe Netherlands

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