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Management of the Clinically Node-Negative Axilla in Primary Breast Cancer

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Personalized Treatment of Breast Cancer
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Abstract

Axillary lymph node status is an important prognostic factor in patients with primary breast cancer. Yet, management of the axilla in these patients has been controversial. Sentinel lymph node biopsy (SLNB) is a less morbid procedure with similar survival and recurrence when compared to axillary lymph node dissection (ALND) and has emerged as the standard of care for staging patients with clinically node-negative disease. The results of three randomized trials seem to suggest that completion ALND may not be necessary in all women with T1/T2 tumors that have sentinel node-positive tumors and a low burden of axillary disease. However, while patients with isolated tumor cells or micrometastatic disease in the sentinel node may forego further axillary treatment, we believe that those with macrometastatic disease on SLNB should undergo additional axillary treatment (either ALND or radiotherapy) until further evidence defining which patients may benefit from observation alone emerges.

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References

  1. Sakorafas GH, Safioleas M (2009) Breast cancer surgery: an historical narrative. Part I. From prehistoric times to Renaissance. Eur J Cancer Care 18(6):530–544

    Article  Google Scholar 

  2. Sakorafas G, Safioleas M (2010) Breast cancer surgery: an historical narrative. Part II. 18th and 19th centuries. Eur J Cancer Care 19(1):6–29

    Article  CAS  Google Scholar 

  3. Virchow R (1863) Cellular pathology (transl. Chance F). Philadelphia, JB Lippincott

    Google Scholar 

  4. Halsted WS (1894) I. The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June, 1889, to January, 1894. Ann Surg 20(5):497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bonadonna G, Valagussa P (1988) The contribution of medicine to the primary treatment of breast cancer. Cancer Res 48(9):2314–2324

    CAS  PubMed  Google Scholar 

  6. Jatoi I, Kaufmann M (2010) Management of breast diseases. Springer, Heidelberg. xvii, 671 p. p

    Book  Google Scholar 

  7. Travis K (2005) Bernard Fisher reflects on a half-century’s worth of breast cancer research. J Natl Cancer Inst 97(22):1636–1637

    Article  PubMed  Google Scholar 

  8. Mittra I (1993) Axillary lymph node metastasis in breast cancer: prognostic indicator or lead-time bias? Eur J Cancer 29(3):300–302

    Article  Google Scholar 

  9. Patani N, Dwek M, Douek M (2007) Predictors of axillary lymph node metastasis in breast cancer: a systematic review. Eur J Surg Oncol (EJSO) 33(4):409–419

    Article  CAS  Google Scholar 

  10. Yoshihara E, Smeets A, Laenen A, Reynders A, Soens J, Van Ongeval C et al (2013) Predictors of axillary lymph node metastases in early breast cancer and their applicability in clinical practice. Breast 22(3):357–361

    Article  PubMed  Google Scholar 

  11. Jatoi I, Hilsenbeck SG, Clark GM, Osborne CK (1999) Significance of axillary lymph node metastasis in primary breast cancer. J Clin Oncol 17(8):2334

    CAS  PubMed  Google Scholar 

  12. Gangi A, Mirocha J, Leong T, Giuliano AE (2014) Triple-negative breast cancer is not associated with increased likelihood of nodal metastases. Ann Surg Oncol 21(13):4098–4103

    Article  PubMed  Google Scholar 

  13. Smeets A, Ryckx A, Belmans A, Wildiers H, Neven P, Floris G et al (2013) Impact of tumor chronology and tumor biology on lymph node metastasis in breast cancer. SpringerPlus 2(1):1–7

    Article  Google Scholar 

  14. Specht MC, Fey JV, Borgen PI, Cody HS 3rd (2005) Is the clinically positive axilla in breast cancer really a contraindication to sentinel lymph node biopsy? J Am Coll Surg 200(1):10–14

    Article  PubMed  Google Scholar 

  15. Sacks N, Baum M (1993) Primary management of carcinoma of the breast. Lancet 342(8884):1402–1408

    Article  CAS  PubMed  Google Scholar 

  16. Harbeck N, Thomssen C (2011) A new look at node-negative breast cancer. Oncologist 16(Suppl 1):51–60

    Article  PubMed  Google Scholar 

  17. Voogd A, Coebergh J-W, Driel OR, Roumen RH, Beek MPM, Vreugdenhil A et al (2000) The risk of nodal metastases in breast cancer patients with clinically negative lymph nodes: a population-based analysis. Breast Cancer Res Treat 62(1):63–69

    Article  CAS  PubMed  Google Scholar 

  18. Nori J, Vanzi E, Bazzocchi M, Bufalini FN, Distante V, Branconi F et al (2007) Role of axillary ultrasound examination in the selection of breast cancer patients for sentinel node biopsy. Am J Surg 193(1):16–20

    Article  PubMed  Google Scholar 

  19. Rajesh Y, Ellenbogen S, Banerjee B (2002) Preoperative axillary ultrasound scan: its accuracy in assessing the axillary nodal status in carcinoma breast. Breast 11(1):49–52

    Article  CAS  PubMed  Google Scholar 

  20. Sapino A, Cassoni P, Zanon E, Fraire F, Croce S, Coluccia C et al (2003) Ultrasonographically-guided fine-needle aspiration of axillary lymph nodes: role in breast cancer management. Br J Cancer 88(5):702–706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cooper KL et al (2011) Positron emission tomography (PET) for assessment of axillary lymph node status in early breast cancer: a systematic review and meta-analysis. Eur J Surg Oncol 37(3):187–198

    Article  CAS  PubMed  Google Scholar 

  22. Harnan SE, Cooper KL, Meng Y, Ward SE, Fitzgerald P, Papaioannou D et al (2011) Magnetic resonance for assessment of axillary lymph node status in early breast cancer: a systematic review and meta-analysis. Eur J Surg Oncol: J Eur Soc Surg Oncol Br Assoc Surg Oncol 37(11):928–936

    Article  CAS  Google Scholar 

  23. Kodama H, Nio Y, Iguchi C, Kan N (2006) Ten-year follow-up results of a randomised controlled study comparing level-I vs level-III axillary lymph node dissection for primary breast cancer. Br J Cancer 95(7):811–816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tominaga T, Takashima S, Danno M (2004) Randomized clinical trial comparing level II and level III axillary node dissection in addition to mastectomy for breast cancer. Br J Surg 91(1):38–43

    Article  CAS  PubMed  Google Scholar 

  25. Axelsson CK, During M, Christiansen PM, Wamberg PA, Soe KL, Moller S (2009) Impact on regional recurrence and survival of axillary surgery in women with node-negative primary breast cancer. Br J Surg 96(1):40–46

    Article  CAS  PubMed  Google Scholar 

  26. Axelsson CK, Mouridsen HT, Zedeler K (1992) Axillary dissection of level I and II lymph nodes is important in breast cancer classification. Eur J Cancer 28(8–9):1415–1418

    Article  Google Scholar 

  27. Party CRCW (1980) Cancer research campaign (King’s/Cambridge) trial for early breast cancer: a detailed update at the tenth year. Lancet 316(8185):55–60

    Google Scholar 

  28. Fisher B, Jeong J-H, Anderson S, Bryant J, Fisher ER, Wolmark N (2002) Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med 347(8):567–575

    Article  PubMed  Google Scholar 

  29. Buchholz TA, Tucker SL, Erwin J, Mathur D, Strom EA, McNeese MD et al (2001) Impact of systemic treatment on local control for patients with lymph node-negative breast cancer treated with breast-conservation therapy. J Clin Oncol: Off J Am Soc Clin Oncol 19(8):2240–2246

    CAS  Google Scholar 

  30. Weaver DL, Rosenberg RD, Barlow WE, Ichikawa L, Carney PA, Kerlikowske K et al (2006) Pathologic findings from the breast cancer surveillance consortium. Cancer 106(4):732–742

    Article  PubMed  Google Scholar 

  31. Rivadeneira DE, Simmons RM, Christos PJ, Hanna K, Daly JM, Osborne MP (2000) Predictive factors associated with axillary lymph node metastases in T1a and T1b breast carcinomas: analysis in more than 900 patients. J Am Coll Surg 191(1):1–6; discussion -8

    Article  CAS  PubMed  Google Scholar 

  32. Bleyer A, Welch HG (2012) Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med 367(21):1998–2005

    Article  CAS  PubMed  Google Scholar 

  33. 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):181–187

    Article  CAS  PubMed  Google Scholar 

  34. Group EBCTC (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365(9472):1687–1717

    Article  Google Scholar 

  35. Kaplan HG, Malmgren JA, Atwood M (2009) T1N0 triple negative breast cancer: risk of recurrence and adjuvant chemotherapy. Breast J 15(5):454–460

    Article  PubMed  Google Scholar 

  36. Nagashima T, Sakakibara M, Nakano S, Tanabe N, Nakamura R, Nakatani Y et al (2006) Sentinel node micrometastasis and distant failure in breast cancer patients. Breast Cancer 13(2):186–191

    Article  PubMed  Google Scholar 

  37. Krag DN, Weaver DL, Alex JC, Fairbank JT (1993) Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol 2(6):335–339; discussion 40

    Article  CAS  PubMed  Google Scholar 

  38. Giuliano AE, Kirgan DM, Guenther JM, Morton DL (1994) Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 220(3):391–398; discussion 8-401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Morrow M, Rademaker AW, Bethke KP, Talamonti MS, Dawes LG, Clauson J et al (1999) Learning sentinel node biopsy: results of a prospective randomized trial of two techniques. Surgery 126(4):714–720; discussion 20-2

    Article  CAS  PubMed  Google Scholar 

  40. Derossis AM, Fey J, Yeung H, Yeh SDJ, Heerdt AS, Petrek J et al (2001) A trend analysis of the relative value of blue dye and isotope localization in 2,000 consecutive cases of sentinel node biopsy for breast cancer1. J Am Coll Surg 193(5):473–478

    Article  CAS  PubMed  Google Scholar 

  41. Cody HS III, Fey J, Akhurst T, Fazzari M, Mazumdar M, Yeung H et al (2001) Complementarity of blue dye and isotope in sentinel node localization for breast cancer: univariate and multivariate analysis of 966 procedures. Ann Surg Oncol 8(1):13–19

    Article  PubMed  Google Scholar 

  42. Linehan DC, Hill AD, Akhurst T, Yeung H, Yeh SD, Tran KN et al (1999) Intradermal radiocolloid and intraparenchymal blue dye injection optimize sentinel node identification in breast cancer patients. Ann Surg Oncol 6(5):450–454

    Article  CAS  PubMed  Google Scholar 

  43. Hung W, Chan C, Ying M, Chong S, Mak K, Yip A (2005) Randomized clinical trial comparing blue dye with combined dye and isotope for sentinel lymph node biopsy in breast cancer. Br J Surg 92(12):1494–1497

    Article  CAS  PubMed  Google Scholar 

  44. McMasters KM, Tuttle TM, Carlson DJ, Brown CM, Noyes RD, Glaser RL et al (2000) Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used. J Clin Oncol 18(13):2560–2566

    CAS  PubMed  Google Scholar 

  45. Hladiuk M, Huchcroft S, Temple W, Schnurr BE (1992) Arm function after axillary dissection for breast cancer: a pilot study to provide parameter estimates. J Surg Oncol 50(1):47–52

    Article  CAS  PubMed  Google Scholar 

  46. Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V et al (2003) A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 349(6):546–553

    Article  PubMed  Google Scholar 

  47. Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Ashikaga T 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(10):881–888

    Article  CAS  PubMed  Google Scholar 

  48. Tsai RJ, Dennis LK, Lynch CF, Snetselaar LG, Zamba GK, Scott-Conner C (2009) The risk of developing arm lymphedema among breast cancer survivors: a meta-analysis of treatment factors. Ann Surg Oncol 16(7):1959–1972

    Article  PubMed  Google Scholar 

  49. Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM et al (2006) Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst 98(9):599–609

    Article  PubMed  Google Scholar 

  50. Gill G (2009) Sentinel-lymph-node-based management or routine axillary clearance? One-year outcomes of Sentinel Node Biopsy Versus Axillary Clearance (SNAC): a randomized controlled surgical trial. Ann Surg Oncol 16(2):266–275

    Article  PubMed  Google Scholar 

  51. Kell MR, Burke JP, Barry M, Morrow M (2010) Outcome of axillary staging in early breast cancer: a meta-analysis. Breast Cancer Res Treat 120(2):441–447

    Article  PubMed  Google Scholar 

  52. Lyman GH, Temin S, Edge SB, Newman LA, Turner RR, Weaver DL et al (2014) Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 32(13):1365–1383

    Article  PubMed  Google Scholar 

  53. van der Ploeg IMC, Nieweg OE, van Rijk MC, Valdés Olmos RA, Kroon BBR (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(12):1277–1284

    Article  PubMed  Google Scholar 

  54. Kim T, Giuliano AE, Lyman GH (2006) Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis. Cancer 106(1):4–16

    Article  PubMed  Google Scholar 

  55. Lyman GH, Giuliano AE, Somerfield MR, Benson AB 3rd, Bodurka DC, Burstein HJ et al (2005) American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol: Off J Am Soc Clin Oncol 23(30):7703–7720

    Article  Google Scholar 

  56. Krag DN, Julian TB, Harlow SP, Weaver DL, Ashikaga T, Bryant J et al (2004) NSABP-32: Phase III, randomized trial comparing axillary resection with sentinal lymph node dissection: a description of the trial. Ann Surg Oncol 11(3):208S–210S

    Article  PubMed  Google Scholar 

  57. van der Ploeg IM, Nieweg OE, van Rijk MC, Valdes Olmos RA, Kroon BB (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: J Eur Soc Surg Oncol Br Assoc Surg Oncol 34(12):1277–1284

    Article  Google Scholar 

  58. Rönkä R, Smitten K, Sintonen H, Kotomäki T, Krogerus L, Leppänen E et al (2004) The impact of sentinel node biopsy and axillary staging strategy on hospital costs. Ann Oncol 15(1):88–94

    Article  PubMed  Google Scholar 

  59. Holck S, Galatius H, Engel U, Wagner F, Hoffmann J (2004) False-negative frozen section of sentinel lymph node biopsy for breast cancer. Breast (Edinb, Scotl) 13(1):42–48

    Article  CAS  Google Scholar 

  60. Classe J, Baffert S, Sigal-Zafrani B, Fall M, Rousseau C, Alran S et al (2012) Cost comparison of axillary sentinel lymph node detection and axillary lymphadenectomy in early breast cancer. A national study based on a prospective multi-institutional series of 985 patients ‘on behalf of the Group of Surgeons from the French Unicancer Federation’. Ann Oncol 23(5):1170–1177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17(6):1471–1474

    Article  PubMed  Google Scholar 

  62. Giuliano AE, Dale PS, Turner RR, Morton DL, Evans SW, Krasne DL (1995) Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg 222(3):394–401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Galimberti V, Cole BF, Zurrida S, Viale G, Luini A, Veronesi P et al (2013) Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol 14(4):297–305

    Article  PubMed  PubMed Central  Google Scholar 

  64. Viale G, Maiorano E, Mazzarol G, Zurrida S, Galimberti V, Luini A et al (2001) Histologic detection and clinical implications of micrometastases in axillary sentinel lymph nodes for patients with breast carcinoma. Cancer 92(6):1378–1384

    Article  CAS  PubMed  Google Scholar 

  65. Giuliano AE, Hawes D, Ballman KV, Whitworth PW, Blumencranz PW, Reintgen DS 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):385–393

    Article  CAS  PubMed  Google Scholar 

  66. Julian T, Anderson S, Krag D, (eds) (2013) 10-year follow-up results of occult detected sentinel node disease: NSABP B-32, a randomized phase III clinical trial to compare sentinel node resection to conventional axillary dissection in clinically node-negative breast cancer patients [Z]. 2013 San Antonio Breast Cancer Symposium, Texas, USA

    Google Scholar 

  67. Network NCC (2014) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): breast cancer. Version 3.2014. 1 Apr 2014

    Google Scholar 

  68. Pilewskie ML, Morrow M (2014) Management of the clinically node-negative axilla: what have we learned from the clinical trials? Oncology (Williston Park, NY) 28(5):371–378

    Google Scholar 

  69. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW et al (2011) Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 305(6):569–575

    Article  CAS  PubMed  Google Scholar 

  70. Shah-Khan M, Boughey JC (2012) Evolution of axillary nodal staging in breast cancer: clinical implications of the ACOSOG Z0011 trial. Cancer Control: J Moffitt Cancer Cent 19(4):267–276

    Google Scholar 

  71. Caudle AS, Hunt KK, Kuerer HM, Meric-Bernstam F, Lucci A, Bedrosian I et al (2011) Multidisciplinary considerations in the implementation of the findings from the American College of Surgeons Oncology Group (ACOSOG) Z0011 study: a practice-changing trial. Ann Surg Oncol 18(9):2407–2412

    Article  PubMed  PubMed Central  Google Scholar 

  72. Jagsi R, Chadha M, Moni J, Ballman K, Laurie F, Buchholz TA et al (2014) Radiation field design in the ACOSOG Z0011 (Alliance) trial. J Clin Oncol 56:5838

    Google Scholar 

  73. Giuliano AE, McCall L, Beitsch P, Whitworth PW, Blumencranz P, Leitch AM 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(3):426–433

    PubMed  Google Scholar 

  74. Zhang XH-F, Giuliano M, Trivedi MV, Schiff R, Osborne CK (2013) Metastasis dormancy in estrogen receptor-positive breast cancer. Clin Cancer Res 19(23):6389–6397

    Article  CAS  PubMed  Google Scholar 

  75. Haffty BG, Hunt KK, Harris JR, Buchholz TA (2011) Positive sentinel nodes without axillary dissection: implications for the radiation oncologist. J Clin Oncol 29(34):4479–4481

    Article  PubMed  Google Scholar 

  76. Straver ME, Meijnen P, van Tienhoven G, van de Velde CJ, Mansel RE, Bogaerts J et al (2010) Role of axillary clearance after a tumor-positive sentinel node in the administration of adjuvant therapy in early breast cancer. J Clin Oncol: Off J Am Soc Clin Oncol 28(5):731–737

    Article  Google Scholar 

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Alarhayem, A.Q., Jatoi, I. (2016). Management of the Clinically Node-Negative Axilla in Primary Breast Cancer. In: Toi, M., Winer, E., Benson, J., Klimberg, S. (eds) Personalized Treatment of Breast Cancer. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55552-0_8

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