Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 8/2013

01-08-2013 | Breast Oncology

The Prognostic Value of Lymph Node Ratio in Node-Positive Breast Cancer: A Dutch Nationwide Population-Based Study

Authors: Pim J. M. Dings, BSc, MD, Marloes A. G. Elferink, MSc, PhD, Luc J. A. Strobbe, MD, PhD, Johannes H. W. de Wilt, MD, PhD

Published in: Annals of Surgical Oncology | Issue 8/2013

Login to get access

Abstract

Background

The absolute number of involved axillary lymph nodes (LNs) is considered the most important prognostic factor in breast cancer. Over the last decade, several studies indicated that the lymph node ratio (LNR) might predict outcome better than the number of positive LNs. In this study we test the applicability of earlier published LNR cutoff values and study the prognostic value of the LNR on a nationwide level.

Methods

A nationwide population-based study was performed, using data from the Netherlands Cancer Registry, including all women diagnosed with node-positive breast cancer between 1999 and 2005 (N = 25,315). Patients were divided into 3 LNR risk groups (low, ≤0.20; intermediate, 0.21–0.65; and high, >0.65). Kaplan–Meier survival analysis was performed. In order to evaluate whether LNR was associated with overall survival (OS), Cox proportional hazards modeling was used.

Results

For the entire cohort, 5- and 10-year OS rates were 78 % and 62 %, respectively. The number of positive LNs correlated with OS (5-year OS 84 %, 72 %, and 55 % for patients with 1–3, 4–9, and 10 or more positive LNs, respectively, P < .001). LNR also correlated with OS (5-year OS 86 %, 75 %, and 54 % for low-, intermediate-, and high-risk groups, respectively, P < .001). In the multivariable analysis, the risk of death increased with increasing LNR (P < .001).

Conclusions

The LNR has an important prognostic value in node-positive patients, independent of traditional clinicopathological factors. LNR should be added as an independent prognostic variable to the current staging system.
Literature
1.
2.
3.
Singletary SE, Allred C, Ashley P, Bassett LW, Berry D, Bland KI, et al. Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol. 2002;20:3628–36.PubMedCrossRef
4.
Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM, et al. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000;124:966–78.PubMed
5.
Rosen PR, Groshen S, Saigo PE, Kinne DW, Hellman S. A long-term follow-up study of survival in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma. J Clin Oncol. 1989;7:355–66.PubMed
6.
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
7.
Beenken SW, Urist MM, Zhang Y, Desmond R, Krontiras H, Medina H, et al. Axillary lymph node status, but not tumor size, predicts locoregional recurrence and overall survival after mastectomy for breast cancer. Ann Surg. 2003;237:732–9.PubMed
8.
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. American Joint Committee on Cancer Staging Manual. 7th edition. New York: Springer; 2010.
9.
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
10.
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
11.
Recht A, Gray R, Davidson NE, Fowble BL, Solin LJ, Cummings FJ, et al. Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group. J Clin Oncol. 1999;17:1689–700.PubMed
12.
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
13.
Petrik DW, McCready DR, Sawka CA, Goel V. Association between extent of axillary lymph node dissection and patient, tumor, surgeon, and hospital factors in patients with early breast cancer. J Surg Oncol. 2003;82:84–90.PubMedCrossRef
14.
Cil T, Hauspy J, Kahn H, Melnick W, Flynn C, Holloway CM. Factors affecting axillary lymph node retrieval and assessment in breast cancer patients. Ann Surg Oncol. 2008;15:3361–8.PubMedCrossRef
15.
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
16.
Woodward WA, Vinh-Hung V, Ueno NT, Cheng YC, Royce M, Tai P, et al. Prognostic value of nodal ratios in node-positive breast cancer. J Clin Oncol. 2006;24:2910–6.PubMedCrossRef
17.
Vinh-Hung V, Verkooijen HM, Fioretta G, Neyroud-Caspar I, Rapiti E, Vlastos G, et al. Lymph node ratio as an alternative to pN staging in node-positive breast cancer. J Clin Oncol. 2009;27:1062–8.PubMedCrossRef
18.
Chagpar AB, Camp RL, Rimm DL. Lymph node ratio should be considered for incorporation into staging for breast cancer. Ann Surg Oncol. 2011;18:3143–8.PubMedCrossRef
19.
Danko ME, Bennett KM, Zhai J, Marks JR, Olson JA, Jr. 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
20.
Ahn SH, Kim HJ, Lee JW, Gong GY, Noh DY, Yang JH, et al. Lymph node ratio and pN staging in patients with node-positive breast cancer: a report from the Korean breast cancer society. Breast Cancer Res Treat. 2011;130:507–15.PubMedCrossRef
21.
Vinh-Hung V, Joseph SA, Coutty N, Ly BH, Vlastos G, Nguyen NP. Age and axillary lymph node ratio in postmenopausal women with T1-T2 node positive breast cancer. Oncologist. 2010;15:1050–62.PubMedCrossRef
22.
Peschaud F, Benoist S, Julie C, Beauchet A, Penna C, Rougier P, et al. The ratio of metastatic to examined lymph nodes is a powerful independent prognostic factor in rectal cancer. Ann Surg. 2008;248:1067–73.PubMedCrossRef
23.
De Ridder M, Vinh-Hung V, Van Nieuwenhove Y, Hoorens A, Sermeus A, Storme G. Prognostic value of the lymph node ratio in node positive colon cancer. Gut. 2006;55:1681.PubMedCrossRef
24.
Peng J, Xu Y, Guan Z, Zhu J, Wang M, Cai G, et al. Prognostic significance of the metastatic lymph node ratio in node-positive rectal cancer. Ann Surg Oncol. 2008;15:3118–23.PubMedCrossRef
25.
Vinh-Hung V, Nguyen NP, Cserni G, Truong P, Woodward W, Verkooijen HM, et al. Prognostic value of nodal ratios in node-positive breast cancer: a compiled update. Future Oncol. 2009;5:1585–603.PubMedCrossRef
26.
Casparie M, Tiebosch AT, Burger G, Blauwgeers H, van de Pol A, van Krieken JH, et al. Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive. Cell Oncol. 2007;29:19–24.PubMed
27.
Wittekind C, Greene FL, Hutter RVP, Klimpfinger M, Sobin LH, eds. TNM Atlas. 5th ed. Berlin: Springer-Verlag; 2004.
28.
Fritz A, Percy C, Jack A, Shanmugarathnam K, Sobin L, Parkin DM, et al. International Classification of Diseases for Oncology. 3rd edition. Geneva: World Health Organization; 2000.
29.
Hermanek P, Hutter RV, Sobin LH, eds. TNM Atlas. 4th ed. Berlin: Springer-Verlag; 1997.
30.
Schouten LJ, Jager JJ, van den Brandt PA. Quality of cancer registry data: a comparison of data provided by clinicians with those of registration personnel. Br J Cancer. 1993;68:974–7.PubMedCrossRef
31.
de Kanter AY, Menke-Pluijmers MB, Henzen-Logmans SC, van Geel AN, van Eijck CJ, Wiggers T, et al. Reasons for failure to identify positive sentinel nodes in breast cancer patients with significant nodal involvement. Eur J Surg Oncol. 2006;32:498–501.PubMedCrossRef
32.
Voogd AC, Nielsen M, Peterse JL, Blichert-Toft M, Bartelink H, Overgaard M, et al. Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials. J Clin Oncol. 2001;19:1688–97.PubMed
33.
Strom EA, Woodward WA, Katz A, Buchholz TA, Perkins GH, Jhingran A, et al. Clinical investigation: regional nodal failure patterns in breast cancer patients treated with mastectomy without radiotherapy. Int J Radiat Oncol Biol Phys. 2005;63:1508–13.PubMedCrossRef
34.
Schiffman SC, McMasters KM, Scoggins CR, Martin RC, Chagpar AB. Lymph node ratio: a proposed refinement of current axillary staging in breast cancer patients. J Am Coll Surg. 2011;213:45–52.PubMedCrossRef
35.
Kiricuta CI, Tausch J. A mathematical model of axillary lymph node involvement based on 1446 complete axillary dissections in patients with breast carcinoma. Cancer. 1992;69:2496–501.PubMedCrossRef
36.
Schaapveld M, Otter R, de Vries EG, Fidler V, Grond JA, van der Graaf WT, et al. Variability in axillary lymph node dissection for breast cancer. J Surg Oncol. 2004;87:4–12.PubMedCrossRef
37.
Lyman GH, Giuliano AE, Somerfield MR, Benson AB 3rd, Bodurka DC, Burstein HJ, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol. 2005;23:7703–20.PubMedCrossRef
38.
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
39.
Krag DN, Single RM. Breast cancer survival according to number of nodes removed. Ann Surg Oncol. 2003;10:1152–9.PubMedCrossRef
40.
41.
Elferink MA, Siesling S, Lemmens VE, Visser O, Rutten HJ, van Krieken JH, et al. Variation in lymph node evaluation in rectal cancer: a Dutch nationwide population-based study. Ann Surg Oncol. 2011;18:386–95.PubMedCrossRef
42.
Elferink MA, Siesling S, Visser O, Rutten HJ, van Krieken JH, Tollenaar RA, et al. Large variation between hospitals and pathology laboratories in lymph node evaluation in colon cancer and its impact on survival, a nationwide population-based study in the Netherlands. Ann Oncol. 2011;22:110–7.PubMedCrossRef
43.
Kyndi M, Sorensen FB, Knudsen H, Overgaard M, Nielsen HM, Overgaard J. Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2008;26:1419–26.PubMedCrossRef
44.
Giuliano AE, McCall L, Beitsch P, Whitworth PW, Blumencranz P, Leitch AM, 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
45.
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.PubMedCrossRef
46.
Francissen CM, Dings PJ, van Dalen T, Strobbe LJ, van Laarhoven HW, de Wilt JH. Axillary recurrence after a tumor-positive sentinel lymph node biopsy without axillary treatment: a review of the literature. Ann Surg Oncol. 2012;19:4140–9.PubMedCrossRef
47.
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
Metadata
Title
The Prognostic Value of Lymph Node Ratio in Node-Positive Breast Cancer: A Dutch Nationwide Population-Based Study
Authors
Pim J. M. Dings, BSc, MD
Marloes A. G. Elferink, MSc, PhD
Luc J. A. Strobbe, MD, PhD
Johannes H. W. de Wilt, MD, PhD
Publication date
01-08-2013
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 8/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-2932-7

Other articles of this Issue 8/2013

Annals of Surgical Oncology 8/2013 Go to the issue

Hepatobiliary Tumors

Perioperative complications influence recurrence and survival after resection of hepatic colorectal metastases

Breast Oncology

The Effect of Age on Race-Related Breast Cancer Survival Disparities

Head and Neck Oncology

Quantitative Shear Wave Elastography as a Prognostic Implication of Papillary Thyroid Carcinoma (PTC): Elasticity Index Can Predict Extrathyroidal Extension (ETE)

Translational Research and Biomarkers

Molecular Staging of Surgical Margins in Oral Squamous Cell Carcinoma Using Promoter Methylation of p16INK4A, Cytoglobin, E-cadherin, and TMEFF2

Hepatobiliary Tumors

Volumetric Changes after 90Y Radioembolization for Hepatocellular Carcinoma in Cirrhosis: An Option to Portal Vein Embolization in a Preoperative Setting?

Endocrine Tumors

The Acceleration in Papillary Thyroid Cancer Incidence Rates is Similar Among Racial and Ethnic Groups in the United States