Breast Cancer Research and Treatment

, Volume 125, Issue 3, pp 893–902 | Cite as

A 10-year follow-up of treatment outcomes in patients with early stage breast cancer and clinically negative axillary nodes treated with tangential breast irradiation following sentinel lymph node dissection or axillary clearance

  • A. Gabriella Wernicke
  • Robert L. Goodman
  • Bruce C. Turner
  • Lydia T. Komarnicky
  • Walter J. Curran
  • Paul J. Christos
  • Imraan Khan
  • Katherine Vandris
  • Bhupesh Parashar
  • Dattatreyudu Nori
  • K. S. Clifford Chao
Brief Report


We compare long-term outcomes in patients with node negative early stage breast cancer treated with breast radiotherapy (RT) without the axillary RT field after sentinel lymph node dissection (SLND) or axillary lymph node dissection (ALND). We hypothesize that though tangential RT was delivered to the breast tissue, it at least partially sterilized occult axillary nodal metastases thus providing low nodal failure rates. Between 1995 and 2001, 265 patients with AJCC stages I–II breast cancer were treated with lumpectomy and either SLND (cohort SLND) or SLND and ALND (cohort ALND). Median follow-up was 9.9 years (range 8.3–15.3 years). RT was administered to the whole breast to the median dose of 48.2 Gy (range 46.0–50.4 Gy) plus boost without axillary RT. Chi-square tests were employed in comparing outcomes of two groups for axillary and supraclavicular failure rates, ipsilateral in-breast tumor recurrence (IBTR), distant metastases (DM), and chronic complications. Progression-free survival (PFS) was compared using log-rank test. There were 136/265 (51%) and 129/265 (49%) patients in the SLND and ALND cohorts, respectively. The median number of axillary lymph nodes assessed was 2 (range 1–5) in cohort SLND and 18 (range 7–36) in cohort ALND (P < 0.0001). Incidence of AFR and SFR in both cohorts was 0%. The rates of IBTR and DM in both cohorts were not significantly different. Median PFS in the SLND cohort is 14.6 years and 10-year PFS is 88.2%. Median PFS in the ALND group is 15.0 years and 10-year PFS is 85.7%. At a 10-year follow-up chronic lymphedema occurred in 5/108 (4.6%) and 40/115 (34.8%) in cohorts SLND and ALND, respectively (P = 0.0001). This study provides mature evidence that patients with negative nodes, treated with tangential breast RT and SLND alone, experience low AFR or SFR. Our findings, while awaiting mature long-term data from NSABP B-32, support that in patients with negative axillary nodal status such treatment provides excellent long-term cure rates while avoiding morbidities associated with ALND or addition of axillary RT field.


Sentinel lymph node sampling Axillary lymph node dissection Breast cancer Tangential breast radiotherapy Radiotherapy 



Axillary failure rates


Sentinel lymph node


Axillary lymph node


Sentinel lymph node dissection


Axillary lymph node dissection


Ipsilateral breast tumor recurrence


Distant metastases


Breast conserving therapy


Supraclavicular failure rates




Estrogen receptor


Progesterone receptor




Modified radical mastectomy



Dr. Paul Christos was partially supported by the following grant: Clinical Translational Science Center (CTSC) (UL1-RR024996).

Conflict of interest



  1. 1.
    Fisher B, Jeong JH, 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):567–575CrossRefPubMedGoogle Scholar
  2. 2.
    Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N (2002) Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347(16):1233–1241CrossRefPubMedGoogle Scholar
  3. 3.
    Veronesi U, Galimberti V, Paganelli G, Maisonneuve P, Viale G, Orecchia R, Luini A, Intra M, Veronesi P, Caldarella P, Renne G, Rotmensz N, Sangalli C, De Brito Lima L, Tullii M, Zurrida S (2009) Axillary metastases in breast cancer patients with negative sentinel nodes: a follow-up of 3548 cases. Eur J Cancer 45(8):1381–1388CrossRefPubMedGoogle Scholar
  4. 4.
    Larson D, Weinstein M, Goldberg I, Silver B, Recht A, Cady B, Silen W, Harris JR (1986) Edema of the arm as a function of the extent of the axillary surgery inpatients with Stage I-II carcinoma of the breast treated with primary radiotherapy. Int J Radiat Oncol Biol Phys 12:1575–1583CrossRefPubMedGoogle Scholar
  5. 5.
    Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM, Yiangou C, Horgan K, Bundred N, Monypenny I, England D, Sibbering M, Abdullah TI, Barr L, Chetty U, Sinnett DH, Fleissig A, Clarke D, Ell PJ (2006) Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: The ALMANAC Trial. J Natl Cancer Inst 98:599–609CrossRefPubMedGoogle Scholar
  6. 6.
    Olson JA Jr, McCall LM, Beitsch P, Whitworth PW, Reintgen DS, Blumencranz PW, Leitch AM, Saha S, Hunt KK (2008) Giuliano AE: Impact of immediate versus delayed axillary node dissection on surgical outcomes in breast cancer patients with positive sentinel nodes: results from American College of Surgeons Oncology Group Trials Z0010 and Z0011. J Clin Oncol 26:3530–3535CrossRefPubMedGoogle Scholar
  7. 7.
    Petrek JA, Heelan MC (1998) Incidence of breast carcinoma-related lymphedema. Cancer 83:2776–2781CrossRefPubMedGoogle Scholar
  8. 8.
    Lucci A, McCall LM, Beitsch PD, Whitworth PW, Reintgen DS, Blumencanz PW, Leitch AM, Saha S, Hunt KK, Giuliano A (2007) Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group Trial Z0011. J Clin Oncol 25:3657–3663CrossRefPubMedGoogle Scholar
  9. 9.
    Goyal A, Newcombe RG, Chhabra A, Mansel RE (2008) Morbidity in breast cancer patients with sentinel node metastases undergoing delayed axillary lymph node dissection (ALND) compared with immediate ALND. Ann Surg Oncol 15(1):262–267CrossRefPubMedGoogle Scholar
  10. 10.
    Giuliano AE, Kirgan DM, Guenther JM, Morton DL (1994) Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 220(3):391–398, 398–401Google Scholar
  11. 11.
    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):335–339CrossRefPubMedGoogle Scholar
  12. 12.
    Veronesi U, Paganelli G, Galimberti V, Viale G, Zurrida S, Bedoni M, Costa A, de Cicco C, Geraghty JG, Luini A, Sacchini V, Veronesi P (1997) Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet 349(9069):1864–1867CrossRefPubMedGoogle Scholar
  13. 13.
    Goodman RL, Grann A, Saracco P, Needham MF (2001) The relationship between radiation fields and regional lymph nodes in carcinoma of the breast. Int J Radiat Oncol Biol Phys 50(1):99–105CrossRefPubMedGoogle Scholar
  14. 14.
    Ribeiro G, Magee B, Swindell R, Harris M, Banerjee SS (1993) The Christie Hospital breast conservation trial: an update at 8 years from inception. Clin Oncol 5:278–283CrossRefGoogle Scholar
  15. 15.
    Wong J, Recht A, Beard CJ, Busse PM, Cady B, Chaffey JT, Come S, Fam S, Kaelin C, Lingos TI, Nixon AJ, Shulman LN, Troyan S, Silver B, Harris JR (1997) Treatment outcome after tangential radiation therapy without axillary dissection in patients with early-stage breast cancer and clinically negative axillary nodes. Int J Radiat Oncol Biol Phys 39:915–920CrossRefPubMedGoogle Scholar
  16. 16.
    Recht A, Houlihan MJ (1995) Axillary lymph nodes and breast cancer. Cancer 76(9):1491–1512CrossRefPubMedGoogle Scholar
  17. 17.
    Berg JW (1955) The significance of axillary node levels in the study of breast carcinoma. Cancer 8(4):776–778CrossRefPubMedGoogle Scholar
  18. 18.
    Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y (2005) Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomized trials. Lancet 366:2087–2106PubMedGoogle Scholar
  19. 19.
    Veronesi U, Marubini E, Del Vecchio M, Manzari A, Andreola S, Greco M, Luini A, Merson M, Saccozzi R, Rilke F (1995) Local recurrences and distant metastases after conservative breast cancer treatments: partly independent events. J Natl Cancer Inst 87:19–27CrossRefPubMedGoogle Scholar
  20. 20.
    Carter CL, Allen C, Henson DE (1989) Relation of tumor size, lymph node status, and survival in 24, 740 breast cancer cases. Cancer 63:181–187CrossRefPubMedGoogle Scholar
  21. 21.
    Orr RK (1999) The impact of prophylactic axillary node dissection on breast cancer survival: a Bayesian meta-analysis. Ann Surg Oncol 6:109–116CrossRefPubMedGoogle Scholar
  22. 22.
    Giuliano AE, Kirgan DM, Guenther JM, Morton DL (1994) Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 220(3):391–398CrossRefPubMedGoogle Scholar
  23. 23.
    Albertini JJ, Lyman GH, Cox C, Yeatman T, Balducci L, Ku N, Shivers S, Berman C, Wells K, Rapaport D, Shons A, Horton J, Greenberg H, Nicosia S, Clark R, Cantor A, Reintgen DS (1996) Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. JAMA 276:1818–1822CrossRefPubMedGoogle Scholar
  24. 24.
    Suami H, Taylor GI, Pan WR (2007) The lymphatic territories of the upper limb: anatomical study and clinical implications. Plast Reconstr Surg 119(6):1813–1822CrossRefPubMedGoogle Scholar
  25. 25.
    Suami H, Pan W-R, Mann B, Taylor GI (2008) The lymphatic anatomy of the breast and its implications for sentinel lymph node biopsy: a human cadaver study. Ann Surg Oncol 15(3):863–871CrossRefPubMedGoogle Scholar
  26. 26.
    Olivier JB, Verhaeghe JL, Butarelli M, Marchal F, Houvenaeghel G (2006) Functional anatomy of the lymphatic drainage of the breast: contribution of sentinel lymph node biopsy. Ann Chir 131(10):608–615CrossRefPubMedGoogle Scholar
  27. 27.
    Pinder SE, Ellis IO, Galea M, O’Rouke S, Blamey RW, Elston CW (1994) Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology 24:41–47CrossRefPubMedGoogle Scholar
  28. 28.
    de Bock GH, van der Hage JA, Putter H, Bonnema J, Bartelink H, van de Velde CJ (2006) Isolated loco-regional recurrence of breast cancer is more common in young patients and following breast conserving therapy: long-term results of European Organization for Research and Treatment of Cancer studies. Eur J Cancer 42(3):351–356CrossRefPubMedGoogle Scholar
  29. 29.
    Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, Intra M, Veronesi P, Robertson C, Maisonneuve P, Renne G, De Cicco C, De Lucia F, Gennari R (2003) A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 349:546–553CrossRefPubMedGoogle Scholar
  30. 30.
    Veronesi U, Viale G, Paganelli G, Zurrida S, Luini A, Galimberti V, Veronesi P, Intra M, Maisonneuve P, Zucca F, Gatt G, Mazzaro G, De Cicco C (2010) Sentinel lymph node biopsy in breast cancer ten-year results of a randomized controlled study. Ann Surg 251:595–600CrossRefPubMedGoogle Scholar
  31. 31.
    Zavagno G, De Salvo GL, Scalco G, Bozza F, Barutta L, Del Bianco P, Renier M, Racano C, Carraro P, Nitti D (2008) A randomized clinical trial on sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer: results of the sentinella/GIVOM trial. Ann Surg 247:207–213CrossRefPubMedGoogle Scholar
  32. 32.
    Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Ashikaga T, Weaver DL, Miller BJ, Jalovec LM, Frazier TG, Noyes RD, Robidoux A, Scarth HM, Mammolito DM, McCready DR, Mamounas EP, Costantino JP, Wolmark N (2007) National Surgical Adjuvant Breast and Bowel Project. 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):881–888CrossRefPubMedGoogle Scholar
  33. 33.
    Harlow SP, Krag DN, Julian TB, Ashikaga T, Weaver DL, Feldman SA, Klimberg VS, Kusminsky R, Moffat FL Jr, Noyes RD, Beitsch PD (2005) Prerandomization Surgical Training for the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial: a randomized phase III clinical trial to compare sentinel node resection to conventional axillary dissection in clinically node-negative breast cancer. Ann Surg 241(1):48–54PubMedGoogle Scholar
  34. 34.
    Ashikaga T, Krag DN, Land SR, Julian TB, Anderson SJ, Brown AM, Skelly JM, Harlow SP, Weaver DL, Mamounas EP, Costantino JP, Wolmark N (2010) National Surgical Adjuvant Breast Bowel Project. Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection. J Surg Oncol 102(2):111–118CrossRefPubMedGoogle Scholar
  35. 35.
    Land SR, Kopec JA, Julian TB, Brown AM, Anderson SJ, Krag DN, Christian NJ, Costantino JP, Wolmark N, Ganz PA (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(25):3929–3936Google Scholar
  36. 36.
    Mansi JL, Gogas H, Bliss JM, Gazet JC, Berger U, Coombes RC (1999) Outcome of primary-breast- cancer patients with micrometastases: a long-term follow-up study. Lancet 354:197–202CrossRefPubMedGoogle Scholar
  37. 37.
    Veronesi U, Orecchia R, Zurrida S, Galimberti V, Luini A, Veronesi P, Gatti G, D’Aiuto G, Cataliotti L, Paolucci R, Piccolo P, Massaioli N, Sismondi P, Rulli A, Lo Sardo F, Recalcati A, Terribile D, Acerbi A, Rotmensz N, Maisonneuve P (2005) Avoiding axillary dissection in breast cancer surgery: a randomized trial to assess the role of axillary radiotherapy. Ann Oncol 16:259–262CrossRefPubMedGoogle Scholar
  38. 38.
    Veronesi U, Galimberti V, Mariani L, Gatti G, Paganelli G, Viale G, Zurrida S, Veronesi P, Intra M, Gennari R, Rita Vento A, Luini A, Tullii M, Bassani G, Rotmensz N (2005) Sentinel node biopsy in breast cancer: early results in 953 patients with negative sentinel node biopsy and no axillary dissection. Eur J Cancer 41:231–237CrossRefPubMedGoogle Scholar
  39. 39.
    Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988CrossRefPubMedGoogle Scholar
  40. 40.
    Hayward JL (1983) New surgical and radiotherapeutic techniques. In: Harris I et al (eds) Conservative management of breast cancer. Lippincott Company, PhiladelphiaGoogle Scholar
  41. 41.
    Smitt M, Goffinet D (1999) Utility of three-dimensional planning for axillary node coverage with breast-conserving radiation therapy: early experience. Radiology 210:221–226PubMedGoogle Scholar
  42. 42.
    Takeda A, Shigematsu N, Kondo M, Amemiya A, Kawaguchi O, Sato M, Kutsuki S, Toya K, Ishibashi R, Kawase T, Tsukamoto N, Kubo A (2000) The modified tangential irradiation technique for breast cancer: how to cover the entire axillary region. Int J Radiat Oncol Biol Phys 46:815–822CrossRefPubMedGoogle Scholar
  43. 43.
    Krasin M, McCall A, King S, Olson M, Emami B (2000) Evaluation of a standard breast tangent technique: a dose-volume analysis of tangential irradiation using three-dimensional tools. Int J Radiat Oncol Biol Phys 47:327–333CrossRefPubMedGoogle Scholar
  44. 44.
    Aristei C, Chionne F, Marsella A, Alessandro M, Rulli A, Lemmi A, Perrucci E, Latini P (2001) Evaluation of level I and II axillary nodes included in the standard breast tangential fields and calculation of the administered dose: results of a prospective study. Int J Radiat Oncol Biol Phys 51:69–73PubMedGoogle Scholar
  45. 45.
    Schlembach PJ, Buchholz TA, Ross MI, Kirsner SM, Salas GJ, Strom EA, McNeese MD, Perkins GH, Hunt KK (2001) Relationship of sentinel and axillary level I-II lymph nodes to tangential fields used in breast irradiation. Int J Radiat Oncol Biol Phys 51:671–678CrossRefPubMedGoogle Scholar
  46. 46.
    Takeda A, Shigematsu N, Ikeda T, Kawaguchi O, Kutsuki S, Ishibashi R, Kunieda E, Takemasa K, Ito H, Uno T, Jinno H, Kubo A (2004) Evaluation of novel modified tangential irradiation technique for breast cancer patients using dose-volume histograms. Int J Radiat Oncol Biol Phys 58(4):1280–1288CrossRefPubMedGoogle Scholar
  47. 47.
    Orecchia R, Huscher A, Leonardi MC, Gennari R, Galimberti C, Garibaldi C, Rondi E, Bianchi LC, Zurrida S, Franzetti S (2005) Irradiation with standard tangential breast fields in patients treated with conservative surgery and sentinel node biopsy: using a three-dimensional tool to evaluate the first level coverage of the axillary nodes. Br J Radiol 78:51–54CrossRefPubMedGoogle Scholar
  48. 48.
    Wong JS, Taghian AG, Bellon JR, Keshaviah A, Smith BL, Winer EP, Silver B, Harris JR (2008) Tangential radiotherapy without axillary surgery in early-stage breast cancer: results of a prospective trial. Int J Radiat Oncol Biol Phys 72(3):866–870CrossRefPubMedGoogle Scholar
  49. 49.
    Rabinovitch R, Ballonoff A, Newman F, Finlayson C (2008) Evaluation of breast sentinel lymph node coverage by standard radiation therapy fields. Int J Radiat Oncol Biol Phys 70(5):1468–1471CrossRefPubMedGoogle Scholar
  50. 50.
    Ohashi T, Takeda A, Shigematsu N, Fukada J, Sanuki N, Amemiya A, Kubo A (2009) Dose distribution analysis of axillary lymph nodes for three-dimensional conformal radiotherapy with a field-in-field technique for breast cancer. Int J Radiat Oncol Biol Phys 73(1):80–87CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • A. Gabriella Wernicke
    • 1
  • Robert L. Goodman
    • 2
  • Bruce C. Turner
    • 3
  • Lydia T. Komarnicky
    • 4
  • Walter J. Curran
    • 5
  • Paul J. Christos
    • 6
  • Imraan Khan
    • 7
  • Katherine Vandris
    • 8
  • Bhupesh Parashar
    • 1
  • Dattatreyudu Nori
    • 1
  • K. S. Clifford Chao
    • 1
  1. 1.Department of Radiation Oncology, Stich Radiation OncologyWeil Cornell Medical College of Cornell UniversityNew YorkUSA
  2. 2.Department of Radiation OncologySaint Barnabas Medical CenterLivingstonUSA
  3. 3.Department of Radiation OncologyThomas Jefferson University HospitalPhiladelphiaUSA
  4. 4.Department of Radiation OncologyDrexel University HospitalPhiladelphiaUSA
  5. 5.Department of Radiation OncologyEmory University School of MedicineAtlantaUSA
  6. 6.Division of Biostatistics and Epidemiology, Department of Public HealthWeill Cornell Medical College of Cornell UniversityNew YorkUSA
  7. 7.Department of Biological SciencesState University of New YorkStony BrookUSA
  8. 8.Division of Hematology/Medical Oncology, Department of MedicineWeill Cornell Medical College of Cornell UniversityNew YorkUSA

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