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
Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2018

01-09-2018 | Clinical trial

Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes

Authors: Yvette Andersson, L. Bergkvist, J. Frisell, J. de Boniface

Published in: Breast Cancer Research and Treatment | Issue 2/2018

Login to get access

Abstract

Purpose

The clinical significance of lymph node micrometastases and isolated tumor cells (ITCs) in breast cancer is still controversial. After a median follow-up of 52 months, a report from the Swedish Multicenter Cohort Study presented a worse cancer-specific and event-free survival for patients with micrometastases than node-negative individuals, but could not demonstrate a significant difference in overall survival (OS). Due to the tendency of breast cancer to relapse after more than 5–10 years, we now report the long-term survival of the cohort.

Methods

Between September 2000 and January 2004, 3355 breast cancer patients were included in a prospective cohort. Sentinel lymph node biopsy was always performed. Patients were classified in four groups according to their overall nodal stage: node negative (N0, 2372), ITCs (113), micrometastases (123), and macrometastases (747). Kaplan–Meier survival estimates and Cox proportional hazard regression models were applied.

Results

Median follow-up was 156 months. Ten-year cancer-specific survival and OS were significantly lower in case of micrometastases than in N0 (84.7 vs. 93.5%, p = 0.001, and 75.5 vs. 84.2%, p = 0.046, respectively). In case of macrometastases, corresponding survival rates were 82.8 and 74.3%. Only for those aged less than 50 years, cancer-specific survival and OS were significantly worse in case of ITCs than N0. Patients with micrometastases received less often chemotherapy than those with macrometastases (24.4 vs. 53.9%).

Conclusions

Lymph node micrometastases in breast cancer have a prognostic significance. This study demonstrates a similar survival for patients with micrometastases and those with macrometastases, possibly due to systemic undertreatment.
Appendix
Available only for authorised users
Literature
1.
Carter CL, Allen C, Henson DE (1989) Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 63(1):181–187CrossRefPubMed
2.
Maaskant AJ, van de Poll-Franse LV, Voogd AC, Coebergh JW, Tutein Nolthenius-Puylaert MC, Nieuwenhuijzen GA (2009) Stage migration due to introduction of the sentinel node procedure: a population-based study. Breast Cancer Res Treat 113(1):173–179CrossRefPubMed
3.
van der Heiden-van der Loo M, Bezemer PD, Hennipman A, Siesling S, van Diest PJ, Bongers V, Peeters PH (2006) Introduction of sentinel node biopsy and stage migration of breast cancer. Eur J Surg Oncol 32(7):710–714CrossRefPubMed
4.
Gobardhan PD, Elias SG, Madsen EV, Bongers V, Ruitenberg HJ, Perre CI, van Dalen T (2009) Prognostic value of micrometastases in sentinel lymph nodes of patients with breast carcinoma: a cohort study. Ann Oncol 20(1):41–48CrossRefPubMed
5.
Houvenaeghel G, Classe JM, Garbay JR, Giard S, Cohen M, Faure C, Charytansky H, Rouzier R, Darai E, Hudry D et al (2016) Survival impact and predictive factors of axillary recurrence after sentinel biopsy. Eur J Cancer 58:73–82CrossRefPubMed
6.
Millis RR, Springall R, Lee AH, Ryder K, Rytina ER, Fentiman IS (2002) Occult axillary lymph node metastases are of no prognostic significance in breast cancer. Br J Cancer 86(3):396–401CrossRefPubMedPubMedCentral
7.
van Roozendaal LM, Schipper RJ, Van de Vijver KK, Haekens CM, Lobbes MB, Tjan-Heijnen VC, de Boer M, Smidt ML (2014) The impact of the pathological lymph node status on adjuvant systemic treatment recommendations in clinically node negative breast cancer patients. Breast Cancer Res Treat 143(3):469–476CrossRefPubMed
8.
Houvenaeghel G, Classe JM, Garbay JR, Giard S, Cohen M, Faure C, Helene C, Belichard C, Uzan S, Hudry D et al (2014) Prognostic value of isolated tumor cells and micrometastases of lymph nodes in early-stage breast cancer: a French sentinel node multicenter cohort study. Breast 23(5):561–566CrossRefPubMed
9.
Jafferbhoy S, McWilliams B (2012) Clinical significance and management of sentinel node micrometastasis in invasive breast cancer. Clin Breast Cancer 12(5):308–312CrossRefPubMed
10.
Salhab M, Patani N, Mokbel K (2011) Sentinel lymph node micrometastasis in human breast cancer: an update. Surg Oncol 20(4):23CrossRef
11.
Chen SL, Hoehne FM, Giuliano AE (2007) The prognostic significance of micrometastases in breast cancer: a SEER population-based analysis. Ann Surg Oncol 14(12):3378–3384CrossRefPubMed
12.
Colleoni M, Rotmensz N, Peruzzotti G, Maisonneuve P, Mazzarol G, Pruneri G, Luini A, Intra M, Veronesi P, Galimberti V et al (2005) Size of breast cancer metastases in axillary lymph nodes: clinical relevance of minimal lymph node involvement. J Clin Oncol 23(7):1379–1389CrossRefPubMed
13.
Gobardhan PD, Elias SG, Madsen EV, van Wely B, van den Wildenberg F, Theunissen EB, Ernst MF, Kokke MC, van der Pol C, Borel Rinkes IH et al (2011) Prognostic value of lymph node micrometastases in breast cancer: a multicenter cohort study. Ann Surg Oncol 18(6):1657–1664CrossRefPubMed
14.
de Boer M, van Dijck JA, Bult P, Borm GF, Tjan-Heijnen VC (2010) Breast cancer prognosis and occult lymph node metastases, isolated tumor cells, and micrometastases. J Natl Cancer Inst 102(6):410–425CrossRefPubMed
15.
Wada N, Imoto S (2008) Clinical evidence of breast cancer micrometastasis in the era of sentinel node biopsy. Int J Clin Oncol 13(1):24–32CrossRefPubMed
16.
Tsuda H (2015) Histological examination of sentinel lymph nodes: significance of macrometastasis, micrometastasis, and isolated tumor cells. Breast Cancer 22(3):221–229CrossRefPubMed
17.
Demicheli R, Abbattista A, Miceli R, Valagussa P, Bonadonna G (1996) Time distribution of the recurrence risk for breast cancer patients undergoing mastectomy: further support about the concept of tumor dormancy. Breast Cancer Res Treat 41(2):177–185CrossRefPubMed
18.
19.
Andersson Y, Frisell J, Sylvan M, de Boniface J, Bergkvist L (2010) Breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes. J Clin Oncol 28(17):2868–2873CrossRefPubMed
20.
Bergkvist L, de Boniface J, Jonsson PE, Ingvar C, Liljegren G, Frisell J (2008) Axillary recurrence rate after negative sentinel node biopsy in breast cancer: three-year follow-up of the Swedish Multicenter Cohort Study. Ann Surg 247(1):150–156CrossRefPubMed
21.
Andersson Y, Frisell J, Sylvan M, de Boniface J, Bergkvist L (2013) Causes of false-negative sentinel node biopsy in patients with breast cancer. Br J Surg 100(6):775–783CrossRefPubMed
22.
Singletary SE, Allred C, Ashley P, Bassett LW, Berry D, Bland KI, Borgen PI, Clark G, Edge SB, Hayes DF et al (2002) Revision of the American Joint Committee on Cancer Staging System for Breast Cancer. J Clin Oncol 20(17):3628–3636CrossRefPubMed
23.
Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ (2011) 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 22(9):1736–1747CrossRefPubMedPubMedCentral
24.
Cox CE, Kiluk JV, Riker AI, Cox JM, Allred N, Ramos DC, Dupont EL, Vrcel V, Diaz N, Boulware D (2008) Significance of sentinel lymph node micrometastases in human breast cancer. J Am Coll Surg 206(2):261–268CrossRefPubMed
25.
Grabau D, Jensen MB, Rank F, Blichert-Toft M (2007) Axillary lymph node micrometastases in invasive breast cancer: national figures on incidence and overall survival. APMIS 115(7):828–837CrossRefPubMed
26.
Kuijt GP, Voogd AC, van de Poll-Franse LV, Scheijmans LJ, van Beek MW, Roumen RM (2005) The prognostic significance of axillary lymph-node micrometastases in breast cancer patients. Eur J Surg Oncol 31(5):500–505CrossRefPubMed
27.
Tan LK, Giri D, Hummer AJ, Panageas KS, Brogi E, Norton L, Hudis C, Borgen PI, Cody III HS (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(11):1803–1809CrossRefPubMed
28.
Truong PT, Vinh-Hung V, Cserni G, Woodward WA, Tai P, Vlastos G (2008) 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 44(12):1670–1677CrossRefPubMed
29.
Iqbal J, Ginsburg O, Giannakeas V, Rochon PA, Semple JL, Narod SA (2017) The impact of nodal micrometastasis on mortality among women with early-stage breast cancer. Breast Cancer Res Treat 161(1):103–115CrossRefPubMed
30.
Giuliano AE, Hawes D, Ballman KV, Whitworth PW, Blumencranz PW, Reintgen DS, Morrow M, Leitch AM, Hunt KK, McCall LM et al (2011) Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer. JAMA 306(4):385–393CrossRefPubMedPubMedCentral
31.
Maaskant-Braat AJ, van de Poll-Franse LV, Voogd AC, Coebergh JW, Roumen RM, Nolthenius-Puylaert MC, Nieuwenhuijzen GA (2011) Sentinel node micrometastases in breast cancer do not affect prognosis: a population-based study. Breast Cancer Res Treat 127(1):195–203CrossRefPubMed
32.
Meattini I, Desideri I, Saieva C, Francolini G, Scotti V, Bonomo P, Greto D, Mangoni M, Nori J, Orzalesi L et al (2014) Impact of sentinel node tumor burden on outcome of invasive breast cancer patients. Eur J Surg Oncol 40(10):1195–1202CrossRefPubMed
33.
Rovera F, Fachinetti A, Rausei S, Chiappa C, Lavazza M, Arlant V, Marelli M, Boni L, Dionigi G, Dionigi R (2013) Prognostic role of micrometastases in sentinel lymph node in patients with invasive breast cancer. Int J Surg 11(1):60022–60029
34.
Weaver DL, Ashikaga T, Krag DN, Skelly JM, Anderson SJ, Harlow SP, Julian TB, Mamounas EP, Wolmark N (2011) Effect of occult metastases on survival in node-negative breast cancer. N Engl J Med 364(5):412–421CrossRefPubMedPubMedCentral
35.
Maibenco DC, Dombi GW, Kau TY, Severson RK (2006) Significance of micrometastases on the survival of women with T1 breast cancer. Cancer 107(6):1234–1239CrossRefPubMed
36.
Montagna E, Viale G, Rotmensz N, Maisonneuve P, Galimberti V, Luini A, Intra M, Veronesi P, Mazzarol G, Pruneri G et al (2009) Minimal axillary lymph node involvement in breast cancer has different prognostic implications according to the staging procedure. Breast Cancer Res Treat 118(2):385–394CrossRefPubMed
37.
Parise CA, Caggiano V (2014) Breast cancer survival defined by the ER/PR/HER2 subtypes and a surrogate classification according to tumor grade and immunohistochemical biomarkers. J Cancer Epidemiol 2014(10):26
38.
Prat A, Pineda E, Adamo B, Galvan P, Fernandez A, Gaba L, Diez M, Viladot M, Arance A, Munoz M (2015) Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast 24(2):5CrossRef
39.
Reis-Filho JS, Pusztai L (2011) Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet 378(9805):1812–1823CrossRefPubMed
40.
Yang ZJ, Yu Y, Hou XW, Chi JR, Ge J, Wang X, Cao XC (2017) The prognostic value of node status in different breast cancer subtypes. OncoTarget 8(3):4563–4571PubMed
41.
42.
Nixon AJ, Neuberg D, Hayes DF, Gelman R, Connolly JL, Schnitt S, Abner A, Recht A, Vicini F, Harris JR (1994) Relationship of patient age to pathologic features of the tumor and prognosis for patients with stage I or II breast cancer. J Clin Oncol 12(5):888–894CrossRefPubMed
43.
de Boer M, van Deurzen CH, van Dijck JA, Borm GF, van Diest PJ, Adang EM, Nortier JW, Rutgers EJ, Seynaeve C, Menke-Pluymers MB et al (2009) Micrometastases or isolated tumor cells and the outcome of breast cancer. N Engl J Med 361(7):653–663CrossRefPubMed
44.
Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, Peto R, Pritchard KI, Bergh J, Dowsett M et al (2017) 20-Year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med 377(19):1836–1846CrossRefPubMedPubMedCentral
Metadata
Title
Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes
Authors
Yvette Andersson
L. Bergkvist
J. Frisell
J. de Boniface
Publication date
01-09-2018
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-018-4820-0

Other articles of this Issue 2/2018

Breast Cancer Research and Treatment 2/2018 Go to the issue

Clinical trial

Intratumoral heterogeneity on dedicated breast positron emission tomography predicts malignancy grade of breast cancer

Epidemiology

Impact of change in body mass index during neoadjuvant chemotherapy and survival among breast cancer subtypes

Preclinical study

Validation of the newly proposed American Joint Committee on Cancer (AJCC) breast cancer prognostic staging group and proposing a new staging system using the National Cancer Database

Clinical trial

Phase I study of alpelisib (BYL-719) and trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC) after trastuzumab and taxane therapy

Epidemiology

Risk-reducing mastectomy rates in the US: a closer examination of the Angelina Jolie effect

Epidemiology

Total and out-of-pocket expenditures among women with metastatic breast cancer in low-deductible versus high-deductible health plans
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits