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Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today?

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Abstract

Evaluation of axillary lymph node status by sentinel lymph node biopsy (SLNB) and complete axillary lymph node dissection (ALND) are an inherent part of breast cancer treatment. Increased understanding of tumor biology has changed the prognostic and therapeutic impact of lymph node status. Non-invasive imaging techniques like axillary ultrasound, FDG-PET, or MRI revealed moderate sensitivity and high specificity in evaluation of lymph node status. Therefore, they are not sufficient for lymph node staging. Otherwise, the impact of remaining micrometastases and even macrometastases for prognosis and treatment decisions is overestimated. Considering tumor biology, the distinction of axillary metastases in isolated tumor cells (ITC, pN0(i+)); micrometastases (pN1mi), and macrometastases (pN1a) is not comprehensible. Increasing data support the thesis that remaining axillary metastases neither increase the axillary recurrence rate nor decrease overall survival. It is doubtful that axillary tumor cells are capable to complete the complex multistep metastatic process. If applied, axillary metastases are sensitive to systemic treatment and are targeted by postoperative tangential breast irradiation. Therefore, the controversy about the clinical relevance of tumor cell clusters or micrometastases in SLN is a sophisticated but not contemporary discussion. Currently, there is no indication for axillary surgery in elderly patients with favorable tumors and clinically tumor-free lymph nodes. Nonetheless, a rational and evidence-based approach to the management of clinically and sonographically N0 patients with planned breast-conserving surgery and limited tumor size is needed now.

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References

  1. Schwartz GF, Guiliano AE, Veronesi U (2002) Proceeding of the consensus conference of the role of sentinel lymph node biopsy in carcinoma or the breast April 19–22, 2001, Philadelphia, PA, USA. Breast J 8:124–138

    Article  PubMed  Google Scholar 

  2. Lyman GH, Giuliano AE, Somerfield MR et al (2005) American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 23:7703–7720

    Article  PubMed  Google Scholar 

  3. Krag DN, Anderson SJ, Julian TB et al (2010) Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol 11:927–933

    Article  PubMed  Google Scholar 

  4. Crane-Okada R, Wascher RA, Elashoff D et al (2008) Long-term morbidity of sentinel node biopsy versus complete axillary dissection for unilateral breast cancer. Ann Surg Oncol 15:1996–2005

    Article  PubMed  Google Scholar 

  5. AGO (2011) Diagnostic and treatment of early and metastatic breast cancer. http://www.ago-online.org

  6. NCCN (National Comprehensive Cancer Network) (2011). NCCN practice guidelines in oncology: breast cancer. Version 02.2011. http://www.nccn.org

  7. Cochrane Collaboration (2010) http://www.cochrane.org

  8. Lanng C, Hoffmann J, Galatius H et al (2007) Assessment of clinical palpation of the axilla as a criterion for performing the sentinel node procedure in breast cancer. Eur J Surg Oncol 33:281–284

    Article  PubMed  CAS  Google Scholar 

  9. Specht MC, Fey JV, Borgen PI et al (2005) Is the clinically positive axilla in breast cancer really a contraindication to sentinel lymph node biopsy? J Am Coll Surg 200:10–14

    Article  PubMed  Google Scholar 

  10. Mathijssen IM, Strijdhorst H, Kiestra SK et al (2006) Added value of ultrasound in screening the clinically negative axilla in breast cancer. J Surg Oncol 94:364–367

    Article  PubMed  CAS  Google Scholar 

  11. Zgajnar J, Hocevar M, Podkrajsek M et al (2006) Patients with preoperatively ultrasonically uninvolved axillary lymph nodes: a distinct subgroup of early breast cancer patients. Breast Cancer Res Treat 97:293–299

    Article  PubMed  Google Scholar 

  12. Boughey JC, Moriarty JP, Degnim AC et al (2010) Cost modeling of preoperative axillary ultrasound and fine-needle aspiration to guide surgery for invasive breast cancer. Ann Surg Oncol 17:953–958

    Article  PubMed  Google Scholar 

  13. Park SH, Kim MJ, Park BW et al (2011) Impact of preoperative ultrasonography and fine-needle aspiration of axillary lymph nodes on surgical management of primary breast cancer. Ann Surg Oncol 18:738–744

    Article  PubMed  Google Scholar 

  14. Baruah BP, Goyal A, Young P et al (2010) Axillary node staging by ultrasonography and fine-needle aspiration cytology in patients with breast cancer. Br J Surg 97:680–683

    Article  PubMed  CAS  Google Scholar 

  15. Alvarez S, Anorbe E, Alcorta P et al (2006) Role of sonography in the diagnosis of axillary lymph node metastases in breast cancer: a systematic review. AJR Am J Roentgenol 186:1342–1348

    Article  PubMed  Google Scholar 

  16. Garcia Fernandez A, Fraile M, Gimenez N et al (2011) Use of axillary ultrasound, ultrasound-fine needle aspiration biopsy and magnetic resonance imaging in the preoperative triage of breast cancer patients considered for sentinel node biopsy. Ultrasound Med Biol 37:16–22

    Article  PubMed  Google Scholar 

  17. Mainiero MB, Cinelli CM, Koelliker SL et al (2010) Axillary ultrasound and fine-needle aspiration in the preoperative evaluation of the breast cancer patient: an algorithm based on tumor size and lymph node appearance. AJR Am J Roentgenol 195:1261–1267

    Article  PubMed  Google Scholar 

  18. Cho N, Moon WK, Han W et al (2009) Preoperative sonographic classification of axillary lymph nodes in patients with breast cancer: node-to-node correlation with surgical histology and sentinel node biopsy results. AJR Am J Roentgenol 193:1731–1737

    Article  PubMed  Google Scholar 

  19. Steppan I, Reimer D, Muller-Holzner E et al (2010) Breast cancer in women: evaluation of benign and malignant axillary lymph nodes with contrast-enhanced ultrasound. Ultraschall Med 31:63–67

    Article  PubMed  CAS  Google Scholar 

  20. Sloka JS, Hollett PD, Mathews M (2007) A quantitative review of the use of FDG-PET in the axillary staging of breast cancer. Med Sci Monit 13:RA37–RA46

    PubMed  Google Scholar 

  21. Peare R, Staff RT, Heys SD (2010) The use of FDG-PET in assessing axillary lymph node status in breast cancer: a systematic review and meta-analysis of the literature. Breast Cancer Res Treat 123:281–290

    Article  PubMed  Google Scholar 

  22. Straver ME, Aukema TS, Olmos RA et al (2010) Feasibility of FDG PET/CT to monitor the response of axillary lymph node metastases to neoadjuvant chemotherapy in breast cancer patients. Eur J Nucl Med Mol Imaging 37:1069–1076

    Article  PubMed  Google Scholar 

  23. Ahn JH, Son EJ, Kim JA et al (2010) The role of ultrasonography and FDG-PET in axillary lymph node staging of breast cancer. Acta Radiol 51:859–865

    Article  PubMed  Google Scholar 

  24. Harada T, Tanigawa N, Matsuki M et al (2007) Evaluation of lymph node metastases of breast cancer using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging. Eur J Radiol 63:401–407

    Article  PubMed  Google Scholar 

  25. Stadnik TW, Everaert H, Makkat S et al (2006) Breast imaging. Preoperative breast cancer staging: comparison of USPIO-enhanced MR imaging and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging for axillary lymph node staging—initial findings. Eur Radiol 16:2153–2160

    Article  PubMed  Google Scholar 

  26. Murray AD, Staff RT, Redpath TW et al (2002) Dynamic contrast enhanced MRI of the axilla in women with breast cancer: comparison with pathology of excised nodes. Br J Radiol 75:220–228

    PubMed  CAS  Google Scholar 

  27. Michel SC, Keller TM, Frohlich JM et al (2002) Preoperative breast cancer staging: MR imaging of the axilla with ultrasmall superparamagnetic iron oxide enhancement. Radiology 225:527–536

    Article  PubMed  Google Scholar 

  28. Memarsadeghi M, Riedl CC, Kaneider A et al (2006) Axillary lymph node metastases in patients with breast carcinomas: assessment with nonenhanced versus uspio-enhanced MR imaging. Radiology 241:367–377

    Article  PubMed  Google Scholar 

  29. Suzuma T, Sakurai T, Yoshimura G et al (2002) MR-axillography oriented surgical sampling for assessment of nodal status in the selection of patients with breast cancer for axillary lymph nodes dissection. Breast Cancer 9:69–74

    Article  PubMed  Google Scholar 

  30. Stets C, Brandt S, Wallis F et al (2002) Axillary lymph node metastases: a statistical analysis of various parameters in MRI with USPIO. J Magn Reson Imaging 16:60–68

    Article  PubMed  Google Scholar 

  31. Kitagawa K, Sakuma H, Ishida N et al (2004) Contrast-enhanced high-resolution MRI of invasive breast cancer: correlation with histopathologic subtypes. AJR Am J Roentgenol 183:1805–1809

    PubMed  Google Scholar 

  32. Bathen TF, Jensen LR, Sitter B et al (2007) MR-determined metabolic phenotype of breast cancer in prediction of lymphatic spread, grade, and hormone status. Breast Cancer Res Treat 104:181–189

    Article  PubMed  Google Scholar 

  33. Gelmon KA (2010) The ongoing debate about nodes. Clin Breast Cancer 10:265–266

    Article  PubMed  Google Scholar 

  34. Tai P, Yu E, Joseph K (2010) Prognostic significance of number of positive nodes: a long-term study of one to two nodes versus three nodes in breast cancer patients. Int J Radiat Oncol Biol Phys 77:180–187

    Article  PubMed  Google Scholar 

  35. Hatoum HA, Jamali FR, El Saghir NS et al (2009) 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 16:3388–3395

    Article  PubMed  Google Scholar 

  36. Crabb SJ, Cheang MC, Leung S et al (2008) Basal breast cancer molecular subtype predicts for lower incidence of axillary lymph node metastases in primary breast cancer. Clin Breast Cancer 8:249–256

    Article  PubMed  Google Scholar 

  37. Van Calster B, Vanden Bempt I, Drijkoningen M et al (2009) Axillary lymph node status of operable breast cancers by combined steroid receptor and HER-2 status: triple positive tumours are more likely lymph node positive. Breast Cancer Res Treat 113:181–187

    Article  PubMed  CAS  Google Scholar 

  38. Wildiers H, Van Calster B, van de Poll-Franse LV et al (2009) Relationship between age and axillary lymph node involvement in women with breast cancer. J Clin Oncol 27:2931–2937

    Article  PubMed  Google Scholar 

  39. Botteri E, Bagnardi V, Goldhirsch A et al (2010) Axillary lymph node involvement in women with breast cancer: does it depend on age? Clin Breast Cancer 10:318–321

    Article  PubMed  Google Scholar 

  40. Kennecke H, Yerushalmi R, Woods R et al (2010) Metastatic behavior of breast cancer subtypes. J Clin Oncol 28:3271–3277

    Article  PubMed  Google Scholar 

  41. Voduc KD, Cheang MC, Tyldesley S et al (2010) Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 28:1684–1691

    Article  PubMed  Google Scholar 

  42. Foulkes WD, Grainge MJ, Rakha EA et al (2009) Tumor size is an unreliable predictor of prognosis in basal-like breast cancers and does not correlate closely with lymph node status. Breast Cancer Res Treat 117:199–204

    Article  PubMed  Google Scholar 

  43. Blows FM, Driver KE, Schmidt MK et al (2010) Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10, 159 cases from 12 studies. PLoS Med 7:e1000279

    Article  PubMed  Google Scholar 

  44. Huber KE, Carey LA, Wazer DE (2009) Breast cancer molecular subtypes in patients with locally advanced disease: impact on prognosis, patterns of recurrence, and response to therapy. Semin Radiat Oncol 19:204–210

    Article  PubMed  Google Scholar 

  45. van de Vijver MJ, He YD, van’t Veer LJ et al (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999–2009

    Article  PubMed  Google Scholar 

  46. Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874

    Article  PubMed  CAS  Google Scholar 

  47. Reimer T, Fietkau R, Markmann S et al (2008) How important is the axillary nodal status for adjuvant treatment decisions at a breast cancer multidisciplinary tumor board? A survival analysis. Ann Surg Oncol 15:472–477

    Article  PubMed  Google Scholar 

  48. Martin M, Segui MA, Anton A et al (2010) Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med 363:2200–2210

    Article  PubMed  CAS  Google Scholar 

  49. Untch M, Gelber RD, Jackisch C et al (2008) Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial. Ann Oncol 19:1090–1096

    Article  PubMed  CAS  Google Scholar 

  50. Engel J, Lebeau A, Sauer H et al (2006) Are we wasting our time with the sentinel technique? Fifteen reasons to stop axilla dissection. Breast 15:452–455

    Article  PubMed  CAS  Google Scholar 

  51. Moon HG, Han W, Noh DY (2010) Comparable survival between pN0 breast cancer patients undergoing sentinel node biopsy and extensive axillary dissection: a report from the Korean Breast Cancer Society. J Clin Oncol 28:1692–1699

    Article  PubMed  Google Scholar 

  52. Kell MR, Burke JP, Barry M et al (2010) Outcome of axillary staging in early breast cancer: a meta-analysis. Breast Cancer Res Treat 120:441–447

    Article  PubMed  Google Scholar 

  53. Land SR, Kopec JA, Julian TB et al (2010) Patient-reported outcomes in sentinel node-negative adjuvant breast cancer patients receiving sentinel-node biopsy or axillary dissection: National Surgical Adjuvant Breast and Bowel Project phase III protocol B-32. J Clin Oncol 28:3929–3936

    Article  PubMed  Google Scholar 

  54. Rudenstam CM, Zahrieh D, Forbes JF et al (2006) Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group Trial 10–93. J Clin Oncol 24:337–344

    Article  PubMed  Google Scholar 

  55. Martelli G, Boracchi P, De Palo M et al (2005) A randomized trial comparing axillary dissection to no axillary dissection in older patients with T1N0 breast cancer: results after 5 years of follow-up. Ann Surg 242:1–6

    Article  PubMed  Google Scholar 

  56. Veronesi U, Orecchia R, Zurrida S et al (2005) Avoiding axillary dissection in breast cancer surgery: a randomized trial to assess the role of axillary radiotherapy. Ann Oncol 16:383–388

    Article  PubMed  CAS  Google Scholar 

  57. Martelli G, Miceli R, Daidone MG et al (2011) Axillary dissection versus no axillary dissection in elderly patients with breast cancer and no palpable axillary nodes: results after 15 years of follow-up. Ann Surg Oncol 18:125–133

    Article  PubMed  Google Scholar 

  58. Fredriksson I, Liljegren G, Arnesson LG et al (2002) Consequences of axillary recurrence after conservative breast surgery. Br J Surg 89:902–908

    Article  PubMed  CAS  Google Scholar 

  59. Louis-Sylvestre C, Clough K, Asselain B et al (2004) Axillary treatment in conservative management of operable breast cancer: dissection or radiotherapy? Results of a randomized study with 15 years of follow-up. J Clin Oncol 22:97–101

    Article  PubMed  Google Scholar 

  60. Bourez R, Rutgers E, van de Velde C (2002) Will we need lymph node dissection at all in the future? Clin Breast Cancer 3:315–322

    Article  PubMed  Google Scholar 

  61. Straver ME, Meijnen P, van Tienhoven G et al (2010) Sentinel node identification rate and nodal involvement in the EORTC 10981–22023 AMAROS trial. Ann Surg Oncol 17:1854–1861

    Article  PubMed  Google Scholar 

  62. Evans SB, Gass J, Wazer DE (2008) Management of the axilla after the finding of a positive sentinel lymph node: a proposal for an evidence-based risk-adapted algorithm. Am J Clin Oncol 31:293–299

    Article  PubMed  Google Scholar 

  63. Krag DN, Anderson SJ, Julian TB et al (2007) Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. Lancet Oncol 8:881–888

    Article  PubMed  CAS  Google Scholar 

  64. Canavese G, Catturich A, Vecchio C et al (1998) Prognostic role of lymph-node level involvement in patients undergoing axillary dissection for breast cancer. Eur J Surg Oncol 24:104–109

    Article  PubMed  CAS  Google Scholar 

  65. Erb KM, Julian TB (2009) Completion of axillary dissection for a positive sentinel node: necessary or not? Curr Oncol Rep 11:15–20

    Article  PubMed  Google Scholar 

  66. Wo JY, Taghian AG, Nguyen PL et al (2010) The association between biological subtype and isolated regional nodal failure after breast-conserving therapy. Int J Radiat Oncol Biol Phys 77:188–196

    Article  PubMed  Google Scholar 

  67. Wapnir IL, Anderson SJ, Mamounas EP et al (2006) Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol 24:2028–2037

    Article  PubMed  Google Scholar 

  68. Giuliano AE, McCall L, Beitsch P et al (2010) 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 252:426–432

    PubMed  Google Scholar 

  69. Giuliano AE, Hunt KK, Ballman KV et al (2011) Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis. JAMA 305:569–575

    Article  PubMed  CAS  Google Scholar 

  70. Yi M, Giordano SH, Meric-Bernstam F et al (2010) Trends in and outcomes from sentinel lymph node biopsy (SLNB) alone vs. SLNB with axillary lymph node dissection for node-positive breast cancer patients: experience from the SEER database. Ann Surg Oncol 17:S343–S351

    Article  Google Scholar 

  71. Bilimoria KY, Bentrem DJ, Hansen NM et al (2009) Comparison of sentinel lymph node biopsy alone and completion axillary lymph node dissection for node-positive breast cancer. J Clin Oncol 27:2946–2953

    Article  PubMed  Google Scholar 

  72. Veronesi U, Marubini E, Mariani L et al (1999) The dissection of internal mammary nodes does not improve the survival of breast cancer patients. 30-year results of a randomised trial. Eur J Cancer 35:1320–1325

    Article  PubMed  CAS  Google Scholar 

  73. Janni W, Rack B, Sommer H et al (2003) Intra-mammary tumor location does not influence prognosis but influences the prevalence of axillary lymph-node metastases. J Cancer Res Clin Oncol 129:503–510

    Article  PubMed  Google Scholar 

  74. Sinha PS, Thrush S, Bendall S et al (2002) Does radical surgery to the axilla give a survival advantage in more severe breast cancer? Eur J Cancer 38:1474–1477

    Article  PubMed  CAS  Google Scholar 

  75. Van Zee KJ, Manasseh DM, Bevilacqua JL et al (2003) A nomogram for predicting the likelihood in breast cancer patients with a positive sentinel node biopsy. Ann Surg Oncol 10:1140–1151

    Article  PubMed  Google Scholar 

  76. Bevilacqua JL, Kattan MW, Fey JV et al (2007) Doctor, what are my chances of having a positive sentinel node? A validated nomogram for risk estimation. J Clin Oncol 25:3670–3679

    Article  PubMed  Google Scholar 

  77. Specht MC, Kattan MW, Fey J et al (2005) Predicting nonsentinel node status after positive sentinel lymph node biopsy for breast cancer: clinicians versus nomogram. Ann Surg Oncol 12:654–659

    Article  PubMed  Google Scholar 

  78. Alran S, De Rycke Y, Fourchotte V et al (2007) Validation and limitations of use of a breast cancer nomogram predicting the likelihood of non-sentinel node involvement after positive sentinel node biopsy. Ann Surg Oncol 14:2195–2201

    Article  PubMed  Google Scholar 

  79. Cserni G, Gregori D, Merletti F et al (2004) Meta-analysis of non-sentinel node metastases associated with micrometastatic sentinel nodes in breast cancer. Br J Surg 91:1245–1252

    Article  PubMed  CAS  Google Scholar 

  80. Langer I, Guller U, Viehl CT et al (2009) Axillary lymph node dissection for sentinel lymph node micrometastases may be safely omitted in early-stage breast cancer patients: long-term outcomes of a prospective study. Ann Surg Oncol 16:3366–3374

    Article  PubMed  Google Scholar 

  81. Sahin AA, Guray M, Hunt KK (2009) Identification and biologic significance of micrometastases in axillary lymph nodes in patients with invasive breast cancer. Arch Pathol Lab Med 133:869–878

    PubMed  Google Scholar 

  82. Cserni G, Amendoeira I, Apostolikas N et al (2003) Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines. Eur J Cancer 39:1654–1667

    Article  PubMed  CAS  Google Scholar 

  83. Turner RR, Weaver DL, Cserni G et al (2008) Nodal stage classification for breast carcinoma: improving interobserver reproducibility through standardized histologic criteria and image-based training. J Clin Oncol 26:258–263

    Article  PubMed  Google Scholar 

  84. Klauber-DeMore N, Van Zee KJ, Linkov I et al (2001) Biological behavior of human breast cancer micrometastases. Clin Cancer Res 7:2434–2439

    PubMed  CAS  Google Scholar 

  85. de Mascarel I, MacGrogan G, Debled M et al (2008) Distinction between isolated tumor cells and micrometastases in breast cancer: is it reliable and useful? Cancer 112:1672–1678

    Article  PubMed  Google Scholar 

  86. Tan LK, Giri D, Hummer AJ et al (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 26:1803–1809

    Article  PubMed  Google Scholar 

  87. Yegiyants S, Romero LM, Haigh PI et al (2010) Completion axillary lymph node dissection not required for regional control in patients with breast cancer who have micrometastases in a sentinel node. Arch Surg 145:564–569

    Article  PubMed  Google Scholar 

  88. Gerber B, Krause A, Muller H et al (2001) Simultaneous immunohistochemical detection of tumor cells in lymph nodes and bone marrow aspirates in breast cancer and its correlation with other prognostic factors. J Clin Oncol 19:960–971

    PubMed  CAS  Google Scholar 

  89. de Boer M, van Deurzen CH, van Dijck JA et al (2009) Micrometastases or isolated tumor cells and the outcome of breast cancer. N Engl J Med 361:653–663

    Article  PubMed  Google Scholar 

  90. van Diest PJ, de Boer M, van Deurzen CH et al (2010) Micrometastases and isolated tumor cells in breast cancer are indeed associated with poorer outcome. J Clin Oncol 28:e140–e142

    Article  PubMed  Google Scholar 

  91. Hansen NM, Grube B, Ye X et al (2009) Impact of micrometastases in the sentinel node of patients with invasive breast cancer. J Clin Oncol 27:4679–4684

    Article  PubMed  Google Scholar 

  92. Reed J, Rosman M, Verbanac KM et al (2009) Prognostic implications of isolated tumor cells and micrometastases in sentinel nodes of patients with invasive breast cancer: 10-year analysis of patients enrolled in the prospective East Carolina University/Anne Arundel Medical Center Sentinel Node Multicenter Study. J Am Coll Surg 208:333–340

    Article  PubMed  Google Scholar 

  93. van der Ploeg I, Nieweg OE, van Rijk MC et al (2008) Axillary recurrence after a tumour-negative sentinel node biopsy in breast cancer patients: a systematic review and meta-analysis of the literature. Eur J Surg Oncol 34:1277–1284

    Article  PubMed  Google Scholar 

  94. Masci G, Di Tommaso L, Del Prato I et al (2010) Sinusal localization of nodal micrometastases is a prognostic factor in breast cancer. Ann Oncol 21:1228–1232

    Article  PubMed  CAS  Google Scholar 

  95. de Boer M, van Dijck JA, Bult P et al (2010) Breast cancer prognosis and occult lymph node metastases, isolated tumor cells, and micrometastases. J Natl Cancer Inst 102:410–425

    Article  PubMed  Google Scholar 

  96. Weaver DL, Ashikaga T, Krag DN et al (2011) Effect of occult metastases on survival in node-negative breast cancer. N Engl J Med 364:412–421

    Article  PubMed  CAS  Google Scholar 

  97. Maaskant-Braat AJ, van de Poll-Franse LV, Voogd AC et al (2010) Sentinel node micrometastases in breast cancer do not affect prognosis: a population-based study. Breast Cancer Res Treat. doi:10.1007/s10549-010-1086-6

  98. Montagna E, Viale G, Rotmensz N et al (2009) Minimal axillary lymph node involvement in breast cancer has different prognostic implications according to the staging procedure. Breast Cancer Res Treat 118:385–394

    Article  PubMed  CAS  Google Scholar 

  99. Gobardhan PD, Elias SG, Madsen EV et al (2009) Prognostic value of micrometastases in sentinel lymph nodes of patients with breast carcinoma: a cohort study. Ann Oncol 20:41–48

    Article  PubMed  CAS  Google Scholar 

  100. Cox CE, Kiluk JV, Riker AI et al (2008) Significance of sentinel lymph node micrometastases in human breast cancer. J Am Coll Surg 206:261–268

    Article  PubMed  Google Scholar 

  101. Nagashima T, Sakakibara M, Nakano S et al (2006) Sentinel node micrometastasis and distant failure in breast cancer patients. Breast Cancer 13:186–191

    Article  PubMed  Google Scholar 

  102. Imoto S, Ochiai A, Okumura C et al (2006) Impact of isolated tumor cells in sentinel lymph nodes detected by immunohistochemical staining. Eur J Surg Oncol 32:1175–1179

    Article  PubMed  CAS  Google Scholar 

  103. Fan YG, Tan YY, Wu CT et al (2005) The effect of sentinel node tumor burden on non-sentinel node status and recurrence rates in breast cancer. Ann Surg Oncol 12:705–711

    Article  PubMed  Google Scholar 

  104. Cyr A, Gillanders WE, Aft RL et al (2010) Micrometastatic disease and isolated tumor cells as a predictor for additional breast cancer axillary metastatic burden. Ann Surg Oncol 17:S303–S311

    Article  Google Scholar 

  105. Tait CR, Dodwell D, Horgan K (2004) Do metastases metastasize? J Pathol 203:515–518

    Article  PubMed  Google Scholar 

  106. Bernards R, Weinberg RA (2002) A progression puzzle. Nature 418:823

    Article  PubMed  CAS  Google Scholar 

  107. Lu X, Yan CH, Yuan M et al (2010) In vivo dynamics and distinct functions of hypoxia in primary tumor growth and organotropic metastasis of breast cancer. Cancer Res 70:3905–3914

    Article  PubMed  CAS  Google Scholar 

  108. Lu X, Kang Y (2007) Organotropism of breast cancer metastasis. J Mammary Gland Biol Neoplasia 12:153–162

    Article  PubMed  Google Scholar 

  109. Smid M, Wang Y, Zhang Y et al (2008) Subtypes of breast cancer show preferential site of relapse. Cancer Res 68:3108–3114

    Article  PubMed  CAS  Google Scholar 

  110. Ran S, Volk L, Hall K et al (2010) Lymphangiogenesis and lymphatic metastasis in breast cancer. Pathophysiology 17:229–251

    Article  PubMed  Google Scholar 

  111. Fisher B, Fisher ER (1966) Transmigration of lymph nodes by tumor cells. Science 152:1397–1398

    Article  PubMed  CAS  Google Scholar 

  112. Krishnan J, Kirkin V, Steffen A et al (2003) Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in tumors and its relationship to lymphatic metastasis in immunocompetent rats. Cancer Res 63:713–722

    PubMed  CAS  Google Scholar 

  113. Hirakawa S, Brown LF, Kodama S et al (2007) VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood 109:1010–1017

    Article  PubMed  CAS  Google Scholar 

  114. Mohammed RA, Green A, El Shikh S et al (2007) Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis. Br J Cancer 96:1092–1100

    Article  PubMed  CAS  Google Scholar 

  115. Nakamura Y, Yasuoka H, Tsujimoto M et al (2005) Lymph vessel density correlates with nodal status, VEGF-C expression, and prognosis in breast cancer. Breast Cancer Res Treat 91:125–132

    Article  PubMed  CAS  Google Scholar 

  116. Yasuoka H, Tsujimoto M, Yoshidome K et al (2008) Cytoplasmic CXCR4 expression in breast cancer: induction by nitric oxide and correlation with lymph node metastasis and poor prognosis. BMC Cancer 8:340

    Article  PubMed  CAS  Google Scholar 

  117. Cabioglu N, Yazici MS, Arun B et al (2005) CCR7 and CXCR4 as novel biomarkers predicting axillary lymph node metastasis in T1 breast cancer. Clin Cancer Res 11:5686–5693

    Article  PubMed  CAS  Google Scholar 

  118. Aitken SJ, Thomas JS, Langdon SP et al (2010) Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases. Ann Oncol 21:1254–1261

    Article  PubMed  CAS  Google Scholar 

  119. Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3:453–458

    Article  PubMed  CAS  Google Scholar 

  120. Wong SY, Hynes RO (2006) Lymphatic or hematogenous dissemination: how does a metastatic tumor cell decide? Cell Cycle 5:812–817

    Article  PubMed  CAS  Google Scholar 

  121. Pantel K, Cote RJ, Fodstad O (1999) Detection and clinical importance of micrometastatic disease. J Natl Cancer Inst 91:1113–1124

    Article  PubMed  CAS  Google Scholar 

  122. Wiedswang G, Borgen E, Schirmer C et al (2006) Comparison of the clinical significance of occult tumor cells in blood and bone marrow in breast cancer. Int J Cancer 118:2013–2019

    Article  PubMed  CAS  Google Scholar 

  123. Bidard FC, Mathiot C, Delaloge S et al (2010) Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann Oncol 21:729–733

    Article  PubMed  Google Scholar 

  124. Bidard FC, Vincent-Salomon A, Sigal-Zafrani B et al (2008) Prognosis of women with stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells. Ann Oncol 19:496–500

    Article  PubMed  Google Scholar 

  125. Schmidt-Kittler O, Ragg T, Daskalakis A et al (2003) From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. Proc Natl Acad Sci USA 100:7737–7742

    Article  PubMed  CAS  Google Scholar 

  126. Schardt JA, Meyer M, Hartmann CH et al (2005) Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancer. Cancer Cell 8:227–239

    Article  PubMed  CAS  Google Scholar 

  127. Theodoropoulos PA, Polioudaki H, Agelaki S et al (2010) Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer. Cancer Lett 288:99–106

    Article  PubMed  CAS  Google Scholar 

  128. Liu S, Wicha MS (2010) Targeting breast cancer stem cells. J Clin Oncol 28:4006–4012

    Article  PubMed  CAS  Google Scholar 

  129. McDermott SP, Wicha MS (2010) Targeting breast cancer stem cells. Mol Oncol 4(5):404–419

    Google Scholar 

  130. Kakarala M, Wicha MS (2008) Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol 26:2813–2820

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Rostock, Suedring 81, 18059, Rostock, Germany

    Bernd Gerber, Kristin Heintze, Johannes Stubert, Max Dieterich, Steffi Hartmann, Angrit Stachs & Toralf Reimer

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  1. Bernd Gerber
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  2. Kristin Heintze
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  3. Johannes Stubert
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  4. Max Dieterich
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  6. Angrit Stachs
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  7. Toralf Reimer
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Correspondence to Bernd Gerber.

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Gerber, B., Heintze, K., Stubert, J. et al. Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today?. Breast Cancer Res Treat 128, 613–624 (2011). https://doi.org/10.1007/s10549-011-1532-0

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  • DOI: https://doi.org/10.1007/s10549-011-1532-0

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