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01-06-2012 | Breast Oncology

Prognostic Value of Number of Removed Lymph Nodes, Number of Involved Lymph Nodes, and Lymph Node Ratio in 7502 Breast Cancer Patients Enrolled onto Trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG)

Authors: Christoph Tausch, MD, Susanne Taucher, MD, Peter Dubsky, MD, Michael Seifert, MD, Roland Reitsamer, MD, Werner Kwasny, MD, Raimund Jakesz, MD, Florian Fitzal, MD, Lidija Filipcic, MSc, Michael Fridrik, MD, Richard Greil, MD, Michael Gnant, MD, FACS

Published in: Annals of Surgical Oncology | Issue 6/2012

Abstract

Purpose

The number of removed axillary lymph nodes and the ratio of involved to removed lymph nodes are described as independent prognostic factors beside the absolute number of involved lymph nodes in breast cancer patients. The correlation between these factors and prognosis were investigated in trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG).

Methods

This retrospective analysis is based on the data of 7052 patients with endocrine-responsive breast cancer who were randomized in four trials of the ABCSG in the years 1990–2006 and underwent axillary lymph node dissection. The prognostic value of number of removed nodes (NRN), number of involved nodes (NIN), and ratio of involved to removed nodes (lymph node ratio, LNR) concerning recurrence-free survival and overall survival was analyzed.

Results

A total of 2718 patients had node-positive disease. No correlation was found between NRN and prognosis. Increasing NIN and LNR were significantly associated with worse recurrence-free survival and overall survival in univariate and multivariate analyses (P < .001). Only in the subgroup of patients with one to three positive lymph nodes and treated with mastectomy (n = 728) was LNR an additional prognostic factor in univariate and multivariate analyses.

Conclusions

For breast cancer patients stringently medicated in the framework of prospective adjuvant clinical trials and requiring a mandatory minimum of removed nodes, NRN does not influence prognosis, and LNR is not superior to NIN as prognostic factor. In patients with one to three positive lymph nodes and mastectomy, LNR could play a role as an additional prognostic factor.

Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989;63:181–7.PubMedCrossRef

Ragaz J, Jackson SM, Le N, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med. 1997;337:956–62.PubMedCrossRef

Hilsenbeck SG, Ravdin PM, de Moor CA, Chamness GC, Osborne CK, Clark GM. Time-dependence of hazard ratios for prognostic factors in primary breast cancer. Breast Cancer Res Treat. 1998;52:227–37.PubMedCrossRef

American Joint Committee on Cancer. AJCC cancer staging manual. 6th ed. New York: Springer-Verlag, 2002.

Goldhirsch A, Glick JH, Gelber RD, Coates AS, Thürlimann B, Senn HJ. Meeting highlights: international expert consensus on the primary therapy of early breast cancer, 2005. Ann Oncol. 2005;16:1569–83.PubMedCrossRef

Vinh-Hung V, Cserni G, Burzykowski T, van de Steene J, Voordeckers M, Storme G. Effect of the number of uninvolved nodes on survival in early breast cancer. Oncol Rep. 2003;10:363–8.PubMed

Axelsson CK, Mouridsen HT, Zedeler K. Axillary dissection of level I and II lymph nodes is important in breast cancer classification. The Danish Breast Cancer Cooperative Group (DBCG). Eur J Cancer. 1992;28A:1415–8.PubMedCrossRef

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;20:1793–9.PubMedCrossRef

Schaapveld M, de Vries EG, van der Graaf WT, Otter R, de Vries J, Willemse PH. The prognostic effect of the number of histologically examined axillary lymph nodes in breast cancer: stage migration or age association? Ann Surg Oncol. 2006;13:465–74.PubMedCrossRef

10.

Blancas I, García-Puche JL, Bermejo B, et al. Low number of examined lymph nodes in node-negative breast cancer patients is an adverse prognostic factor. Ann Oncol. 2006;17:1644–9.PubMedCrossRef

11.

Kuru B, Bozgul M. The impact of axillary lymph nodes removed in staging of node-positive breast carcinoma. Int J Radiat Oncol Biol Phys. 2006;66:1328–34.PubMedCrossRef

12.

Voordeckers M, Van de Steene J, Vinh-Hung V, Storme G. Adjuvant radiotherapy after mastectomy for pT1–pT2 node negative (pN0) breast cancer: is it worth the effort? Radiother Oncol. 2003;68:227–31.PubMedCrossRef

13.

Karlsson P, Cole BF, Price KN, Coates AS, et al. The role of the number of uninvolved lymph nodes in predicting locoregional recurrence in breast cancer. J Clin Oncol. 2007;25:2019–26.PubMedCrossRef

14.

Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg. 2010;252:426–32.PubMed

15.

Giuliano AE, Hunt KK, Ballman KV, 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.PubMedCrossRef

16.

Jakesz R, Hausmaninger H, Kubista E, et al. Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer—Austrian Breast and Colorectal Cancer Study Group Trial 5. J Clin Oncol. 2002;20:4621–7.PubMedCrossRef

17.

Schmid M, Jakesz R, Samonigg H, et al. Randomized trial of tamoxifen versus tamoxifen plus aminoglutethimide as adjuvant treatment in postmenopausal breast cancer patients with hormone receptor-positive disease: Austrian breast and colorectal cancer study group trial 6. J Clin Oncol. 2003;21:984–90.PubMedCrossRef

18.

Jakesz R, Greil R, Gnant M, et al. Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. J Natl Cancer Inst. 2007;99:1845–53.PubMedCrossRef

19.

Jakesz R, Jonat W, Gnant M, et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005;366(9484):455–62.PubMedCrossRef

20.

Gnant M, Mlineritsch B, Schippinger W, et al.; ABCSG-12 Trial Investigators. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 2009;360:679–91.PubMedCrossRef

21.

Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347:567–75.PubMedCrossRef

22.

Orr RK. The impact of prophylactic axillary node dissection on breast cancer survival—a Bayesian meta-analysis. Ann Surg Oncol. 1999;6:109–16.PubMedCrossRef

23.

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;72:365–7.PubMedCrossRef

24.

Graversen HP, Blichert-Toft M, Andersen JA, Zedeler K. Breast cancer: risk of axillary recurrence in node-negative patients following partial dissection of the axilla. Eur J Surg Oncol. 1988;14:407–12.PubMed

25.

Krag DN, Single RM. Breast cancer survival according to number of nodes removed. Ann Surg Oncol. 2003;10:1152–9.PubMedCrossRef

26.

Moorman PG, Hamza A, Marks JR, Olson JA. Prognostic significance of the number oflymph nodes examined in patients with lymph node–negative breast carcinoma. Cancer. 2001;91:2258–62.PubMedCrossRef

27.

Truong PT, Berthelet E, Lee J, Kader HA, Olivotto IA. The prognostic significance of the percentage of positive/dissected axillary lymph nodes in breast cancer recurrence and survival in patients with one to three positive axillary lymph nodes. Cancer. 2005;103:2006–14.PubMedCrossRef

28.

Truong PT, Vinh-Hung V, Cserni G, Woodward WA, Tai P, Vlastos G. The number of positive nodes and the ratio of positive to excised nodes are significant predictors of survival in women with micrometastatic node-positive breast cancer. Eur J Cancer. 2008;44:1670–7.PubMedCrossRef

29.

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;88:108–13.PubMedCrossRef

30.

Iyer RV, Hanlon A, Fowble B, et al. Accuracy of the extent of axillary nodal positivity related to primary tumor size, number of involved nodes, and number of nodes examined. Int J Radiat Oncol Biol Phys. 2000;47:1177–83.PubMedCrossRef

31.

van der Wal BC, Butzelaar RM, van der Meij S, Boermeester MA. Axillary lymph node ratio and total number of removed lymph nodes: predictors of survival in stage I and II breast cancer. Eur J Surg Oncol. 2002;28:481–9.PubMedCrossRef

32.

Fortin A, Dagnault A, Blondeau L, Vu TT, Larochelle M. The impact of the number of excised axillary nodes and of the percentage of involved nodes on regional nodal failure in patients treated by breast-conserving surgery with or without regional irradiation. Int J Radiat Oncol Biol Phys. 2006;65:33–9.PubMedCrossRef

33.

Megale Costa LJ, Soares HP, Gaspar HA, et al. Ratio between positive lymph nodes and total dissected axillaries lymph nodes as an independent prognostic factor for disease-free survival in patients with breast cancer. Am J Clin Oncol. 2004;27:304–6.PubMedCrossRef

34.

Hatoum HA, Jamali FR, El-Saghir NS, et al. Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with nonmetastatic lymph node–positive breast cancer. Ann Surg Oncol. 2009;16:3388–95.PubMedCrossRef

35.

Keam B, Im SA, Kim HJ, et al. Clinical significance of axillary nodal ratio in stage II/III breast cancer treated with neoadjuvant chemotherapy. Breast Cancer Res Treat. 2009;116:153–60.PubMedCrossRef

36.

Danko ME, Bennett KM, Zhai J, Marks JR, Olson JA. Improved staging in node-positive breast cancer patients using lymph node ratio: results in 1,788 patients with long-term follow-up. J Am Coll Surg. 2010;210:797–807.PubMedCrossRef

37.

Kühn T. Sentinel lymph node biopsy in early breast cancer. Breast Care. 2011;6:185–91.PubMedCrossRef

38.

Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ. Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer, 2011. Ann Oncol. 2011;22:1736–47.PubMedCrossRef

39.

Abrams JS. Adjuvant therapy for breast cancer—results from the USA consensus conference. Breast Cancer. 2001;8:298–304.PubMedCrossRef

40.

Clarke M, Collins R, Darby S, et al.; Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366:2087–106.PubMed

41.

Chung CS, Harris JR. Post-mastectomy radiation therapy: translating local benefits into improved survival. Breast. 2007;16(Suppl 2):S78–83.PubMedCrossRef

42.

Cosar R, Uzal C, Tokatli F, et al. Postmastectomy irradiation in breast in breast cancer patients with T1–2 and 1–3 positive axillary lymph nodes: is there a role for radiation therapy? Radiat Oncol. 201130;6:28.

43.

Wu SG, He ZY, Li FY, et al. The clinical value of adjuvant radiotherapy in patients with early stage breast cancer with 1 to 3 positive lymph nodes after mastectomy. Chin J Cancer. 2010;29:668–76.PubMed

44.

Overgaard M, Nielsen HM, Overgaard J. Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b&c randomized trials. Radiother Oncol. 2007;82:247–53.PubMedCrossRef

45.

Title: Prognostic Value of Number of Removed Lymph Nodes, Number of Involved Lymph Nodes, and Lymph Node Ratio in 7502 Breast Cancer Patients Enrolled onto Trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG)
Authors: Christoph Tausch, MD
Susanne Taucher, MD
Peter Dubsky, MD
Michael Seifert, MD
Roland Reitsamer, MD
Werner Kwasny, MD
Raimund Jakesz, MD
Florian Fitzal, MD
Lidija Filipcic, MSc
Michael Fridrik, MD
Richard Greil, MD
Michael Gnant, MD, FACS
Publication date: 01-06-2012
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 6/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-011-2189-y

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Prognostic Value of Number of Removed Lymph Nodes, Number of Involved Lymph Nodes, and Lymph Node Ratio in 7502 Breast Cancer Patients Enrolled onto Trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG)

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

Purpose

Methods

Results

Conclusions

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