The association between lymph node status and the tumor size in breast cancer – results from the Danish Breast Cancer Group (DBCG)
DOI:
https://doi.org/10.2340/1651-226X.2025.43380Keywords:
Breast cancer, lymphatic metastases, subtypes, algorithmAbstract
Background and purpose: The association between the tumor size and the risk of lymph node metastasis (LNM) is well known. The purpose of this study is to describe a new model for predicting the occurrence of LNM at an earlier time for breast cancer patients where at a given time this association is known.
Patient/material and methods: The subjects studied were 59,400 breast cancer patients treated in the period 1995–2012 and registered in the Danish Breast Cancer Group (DBCG) database. Data included age, year of treatment, menopausal status, tumor size, lymph node status, localization, focality, histological type, grade, estrogen receptor (ER), HER2 status, lympho-vascular invasion (LVI), and type of surgery. Univariate and multivariate analyses were made.
Results: 46% of patients presented with LNM. The occurrence increased with increasing tumor size. HER2 positive tumors had more LNM 56.9% versus 44.7% (p < 0.001) (odds ratio [OR] 1.17 [95% confidence interval, CI 1.09–1.26]) and mostly pronounced in relation to ER negative tumors (p < 0.001). ER negative/HER2 negative tumors had lower risk of LNM (OR 0.57 [95% CI 0.52–0.63]). Central tumors and tumors in the lower lateral quadrant were more often node positive. LVI showed increased odds for LNM (OR 5.16 [95% CI 4.84–5.52]).
Interpretation: Increasing tumor size is the only time-dependent risk of LNM. HER2 positive tumors had an increased risk of LNM, and ER negative/HER2 negative tumors had a decreased risk of LNM. LVI was associated with substantial increased risk of LNM. The knowledge of breast cancer patient and tumor characteristics at a given time may predict stage of cancer at an earlier time.
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Yoshihara E, Smeets A, Laenen A, Reynders A, Soens J, Ongeval CV, et al. Predictors of axillary lymph node metastases in early breast cancer and their applicability in clinical practice. Breast. 2013;22:357–61.
https://doi.org/10.1016/j.breast.2012.09.003 DOI: https://doi.org/10.1016/j.breast.2012.09.003
Fields RC, Jeffe DB, Deshpande AD, Feunou F, Krishna N, Margenthaler JA. Predictors of axillary lymph node involvement in women with T3 breast cancers: analysis of 1988–2003 SEER Data. J Surg Res. 2010;161:183–9.
https://doi.org/10.1016/j.jss.2009.08.014 DOI: https://doi.org/10.1016/j.jss.2009.08.014
Cortesi L, Marcheselli L, Guarneri V, Cirilli C, Braghiroli B, Toss A, et al. Tumor size, node status, grading, HER2 and estrogen receptor status still retain a strong value in patients with operable breast cancer diagnosed in recent years. Int J Cancer. 2013;132:E58–65.
https://doi.org/10.1002/ijc.27795 DOI: https://doi.org/10.1002/ijc.27795
Takada K, Kashiwagi S, Asano Y, Goto W, Kouhashi R, Yabumoto A, et al. Prediction of lymph node metastases by tumor-infiltrating lympho-cytes in T1 breast cancer. BMC. 2020;20:598.
https://doi.org/10.1186/s12885-020-07101-y DOI: https://doi.org/10.1186/s12885-020-07101-y
Elleson KM, Englander K, Gallagher J, Chintapallly N, Sun W, Whiting J, et al. Factors predictive of positive lymph nodes for breast cancer. Curr Oncol. 2023;30:10351–62.
https://doi.org/10.3390/curroncol30120754 DOI: https://doi.org/10.3390/curroncol30120754
Tresserra F, Rodriguez I, Garcia-Yuste M, Grases PJ, Ara C, Fabregas R. Tumor size and lymph node status in multifocal breast cancer. Breast J. 2007;13(1):68–71.
https://doi.org/10.1111/j.1524-4741.2006.00365.x DOI: https://doi.org/10.1111/j.1524-4741.2006.00365.x
Bucchi L, Barchielli A, Ravaioli A, Federico M, Lisi VD, Ferretti S, et al. Screen-detected vs clinical breast cancer: the advantage in the relative risk of lymph node metastases decreases with increasing tumor size. Br J Cancer. 2005;92:156–61.
https://doi.org/10.1038/sj.bjc.6602289 DOI: https://doi.org/10.1038/sj.bjc.6602289
Holm-Rasmussen EV, Jensen M, Balslev E, Kroman N, Tvedskov T. Reduced risk of axillary lymphatic spread in triple-negative breast cancer. Breast Cancer Res Treat. 2015;149:229–36.
https://doi.org/10.1007/s10549-014-3225-y DOI: https://doi.org/10.1007/s10549-014-3225-y
Greer LT, Rosman M, Mylander C, Liang W, Buras RR, Chagpar AB, et al. A prediction model for the presence of axillary lymph node in-volvement in women with invasive breast cancer: a focus on older women. Breast J. 2014;20(2):147–53.
https://doi.org/10.1111/tbj.12233 DOI: https://doi.org/10.1111/tbj.12233
Peer PGM, Dijck JAAM, Hendriks JHCL, Holland R, Verbeek ALM. Age-dependent growth rate of primary breast cancer. Cancer. 1993;71:3547–51.
https://doi.org/10.1002/1097-0142(19930601)71:11<3547::AID-CNCR2820711114>3.0.CO;2-C DOI: https://doi.org/10.1002/1097-0142(19930601)71:11<3547::AID-CNCR2820711114>3.0.CO;2-C
Meretoja TJ, Heikkila PS, Mansfield AS, Cserni G, Ambrozay E, Boross G, et al. A predictive tool to estimate the risk of axillary metastases in breast cancer patients with negative axillary ultrasound. Ann Surg Oncol. 2014;21:2229–36.
https://doi.org/10.1245/s10434-014-3617-6 DOI: https://doi.org/10.1245/s10434-014-3617-6
Mehrara E, Forssell-Aronsson E, Ahlman H, Bernhardt P. Specific growth rate versus doubling time for quantitative characterization of tumor growth rate. Cancer Res. 2007;67(8):3970–5.
https://doi.org/10.1158/0008-5472.CAN-06-3822 DOI: https://doi.org/10.1158/0008-5472.CAN-06-3822
Tvedskov T, Jensen M, Balslev E, Kroman N. Robust and validated models to predict high risk of non-sentinel node metastases in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node. Acta Oncol. 2014;53:209–15.
https://doi.org/10.3109/0284186X.2013.806993 DOI: https://doi.org/10.3109/0284186X.2013.806993
Meretoja TJ, Strien L, Heikkila PS, Leidenius MHK. A simple nomogram to evaluate the risk of nonsentinel node metastases in breast cancer patients with minimal sentinel node involvement. Ann Surg Oncol. 2012;19:567–76.
https://doi.org/10.1245/s10434-011-1882-1 DOI: https://doi.org/10.1245/s10434-011-1882-1
Isheden G, Czene K, Humphreys K. Random effects models of lymph node metastases in breast cancer: quantifying the roles of covariates and screening using a continous growth model. Biometric Pract. 2022;78:376–87.
https://doi.org/10.1111/biom.13430 DOI: https://doi.org/10.1111/biom.13430
Sopik V, Narod SA. The relationship between tumour size, nodal status and distant metastases: on the origins of breast cancer. Breast Cancer Res Treat. 2018;170(3):647–56.
https://doi.org/10.1007/s10549-018-4796-9 DOI: https://doi.org/10.1007/s10549-018-4796-9
Bevilacqua JLB, Kattan MW, Fey JV, Cody III HS, Borgen PI, Zee KJ. Doctor, what are my chances of having a positive sentinel node? A validated nomogram for risk estimation. J Clin Oncol. 2007;25(24):3670–9.
https://doi.org/10.1200/JCO.2006.08.8013 DOI: https://doi.org/10.1200/JCO.2006.08.8013
Malter W, Hellmich M, Badian M, Kirn V, Mallmann P, Kramer S. Factors predictive of sentinel lymph node involvement in primary breast cancer. Anticancer Res. 2018;38:3657–62.
https://doi.org/10.21873/anticanres.12642 DOI: https://doi.org/10.21873/anticanres.12642
Bevilacqua JLB, Gucciardo G, Cody III HS, MacDonald KA, Sacchini V, Borgen PI, et al. A selection algorithm for internal mammary sentinel lymph node biopsy in breast cancer. Eur J Surg Oncol. 2002;28:603–14.
https://doi.org/10.1053/ejso.2002.1269 DOI: https://doi.org/10.1053/ejso.2002.1269
Bevilacqua JLB, Cody III HS, MacDonald KA, Tan LK, Borgen PI, Zee KJ. A model for predicting axillary node metastases based on 2000 senti-nel node procedures and tumour position. Eur J Surg Oncol. 2002;28:490–500.
https://doi.org/10.1053/ejso.2002.1268 DOI: https://doi.org/10.1053/ejso.2002.1268
Lohrisch C, Jackson J, Jones A, Mates D, Olivotto IA. Relationship between tumor location and relapse in 6,781 women with early invasive breast cancer. J Clin Oncol. 2000;18(15):2828–35.
https://doi.org/10.1200/JCO.2000.18.15.2828 DOI: https://doi.org/10.1200/JCO.2000.18.15.2828
Christiansen P, Carstensen SL, Ejlertsen B, Kroman N, Offersen B, Bodilsen A, et al. Breast conserving surgery versus mastectomy: overall and relative survival – a population based study by the Danish Breast Cancer Cooperative Group (DBCG). Acta Oncolol. 2018 Jan; 57(1): 19-25.
https://doi.org/10.1080/0284186X.2017.1403042 DOI: https://doi.org/10.1080/0284186X.2017.1403042
Nakashima K, Uematsu T, Takahashi K, Nishimura S, Tadokoro Y, Hayashi T, et al. Does breast cancer growth rate really depend on tumor subtype? Measurement of tumor doubling time using serial ultrasonography between diagnosis and surgery. Breast Cancer. 2019;26(2):206–14.
https://doi.org/10.1007/s12282-018-0914-0 DOI: https://doi.org/10.1007/s12282-018-0914-0
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Copyright (c) 2025 Tanja L. Fris, Marianne D. Lautrup, Peer M. Christiansen
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