Advertisement

Annals of Surgical Oncology

, Volume 23, Issue 10, pp 3310–3316 | Cite as

Lymph Node Ratio Analysis After Neoadjuvant Chemotherapy is Prognostic in Hormone Receptor-Positive and Triple-Negative Breast Cancer

  • Jacqueline Tsai
  • Danielle Bertoni
  • Tina Hernandez-Boussard
  • Melinda L. Telli
  • Irene L. WapnirEmail author
Breast Oncology

Abstract

Background

Lymph node ratios (LNR), the proportion of positive lymph nodes over the number excised, both defined as ranges and single ratio values are prognostic of outcome. Little is known of the prognostic value of LNR after neoadjuvant chemotherapy (NAC) according to molecular subtype.

Methods

From 2003 to 2014, patients who underwent definitive surgery after NAC were identified. LNR was calculated for node-positive patients who received axillary dissection or had at least 6 nodes removed. DFS was calculated using the Kaplan-Meier log rank test for yp N0-3 status, LNR categories (LNRC) ≤0.20 (low), 0.21–0.65 (intermediate), >0.65 (high), and single LNR values.

Results

Of 428 NAC recipients, 263 were node negative and 165 (38.6 %) node positive: ypN1 = 97 (58.8 %), ypN2 = 43 (26.1 %), and ypN3 = 25 (15.2 %). Among node-positive cancers, the median number of LN removed was 14 (range, 6–51) and the median LNR was 0.22 (range, 0.03–1.0). Nodal stage was inversely associated with 5-year DFS: 91.5 % (ypN0), 74.5 % (ypN1), 49.8 % (ypN2), and 50.7 % (ypN3) (p < 0.001). LNRC was similarly inversely associated with DFS: 69.1 % (low), 71.4 % (intermediate), 49.3 % (high) (p < 0.001). Significant associations between LNRC and DFS were demonstrated in hormone receptor (HR)-positive and triple negative breast cancer (TNBC) subtypes, p = 0.02 and p = 0.003. A single-value LNR ≤ 0.15 in node-positive, HR-positive (94.1 vs 67.7 %; p = 0.04) and TNBC (94.1 vs 47.8 %; p = 0.001) groups was also significant.

Conclusions

Residual nodal disease after NAC, analyzed by LNRC or LNR = 0.15 cutoff value, is prognostic and can discriminate between favorable and unfavorable outcomes for HR-positive and TNBC cancers.

Keywords

Axillary Node Dissection Triple Negative Breast Cancer Lymph Node Ratio Residual Cancer Burden Triple Negative Breast Cancer Subtype 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Supplementary material

10434_2016_5319_MOESM1_ESM.docx (63 kb)
Supplementary material 1 (DOCX 64 kb)

References

  1. 1.
    Fisher B, Bauer M, Wickerham DL, et al. Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer. 1983;52:1551–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989;63:181–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72. doi: 10.1016/S0140-6736(13)62422-8.CrossRefPubMedGoogle Scholar
  4. 4.
    Bear HD, Anderson S, Smith RE, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006;24:2019–27. doi: 10.1200/JCO.2005.04.1665.CrossRefPubMedGoogle Scholar
  5. 5.
    Greene FL, Balch CM, Fleming ID, et al. Cancer AJCO. AJCC cancer staging handbook. New York: Springer; 2002.Google Scholar
  6. 6.
    Carey LA, Metzger R, Dees EC, et al. American Joint Committee on Cancer tumor-node-metastasis stage after neoadjuvant chemotherapy and breast cancer outcome. J Natl Cancer Inst. 2005;97:1137–42. doi: 10.1093/jnci/dji206.CrossRefPubMedGoogle Scholar
  7. 7.
    Sosa JA, Diener-West M, Gusev Y, Choti MA, Lange JR, Dooley WC, Zeiger MA. Association between extent of axillary lymph node dissection and survival in patients with stage I breast cancer. Ann Surg Oncol. 1998;5:140–9.CrossRefPubMedGoogle Scholar
  8. 8.
    van der Wal BCH, Butzelaar RMJM, van der Meij S, Boermeester MA. Axillary lymph node ratio and total number of removed lymph nodes: predictors of survival in stage I and II breast cancer. Eur J Surg Oncol. 2002;28:481–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Voordeckers M, Vinh-Hung V, van de Steene J, Lamote J, Storme G. The lymph node ratio as prognostic factor in node-positive breast cancer. Radiother Oncol. 2004;70:225–30. doi: 10.1016/j.radonc.2003.10.015.CrossRefPubMedGoogle Scholar
  10. 10.
    Schiffman SC, McMasters KM, Scoggins CR, Martin RC, Chagpar AB. Lymph node ratio: a proposed refinement of current axillary staging in breast cancer patients. J Am Coll Surg. 2011;213:45–52; discussion 52–3. doi: 10.1016/j.jamcollsurg.2011.04.024.
  11. 11.
    Wiznia LE, Lannin DR, Evans SB, et al. The number of lymph nodes dissected in breast cancer patients influences the accuracy of prognosis. Ann Surg Oncol. 2014;21:389–94. doi: 10.1245/s10434-013-3308-8.CrossRefPubMedGoogle Scholar
  12. 12.
    Vinh-Hung V, Verkooijen HM, Fioretta G, et al. Lymph node ratio as an alternative to pN staging in node-positive breast cancer. J Clin Oncol. 2009;27:1062–8. doi: 10.1200/JCO.2008.18.6965.CrossRefPubMedGoogle Scholar
  13. 13.
    Truong PT, Vinh-Hung V, Cserni G, et al. 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. 2008;44:1670–7. doi: 10.1016/j.ejca.2008.05.011.CrossRefPubMedGoogle Scholar
  14. 14.
    Vinh-Hung V, Verschraegen C. Breast-conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst. 2004;96:115–21.CrossRefPubMedGoogle Scholar
  15. 15.
    Danko ME, Bennett KM, Zhai J, Marks JR, Olson JA. Improved staging in node-positive breast cancer patients using lymph node ratio: results in 1,788 patients with long-term follow-up. J Am Coll Surg. 2010;210:797–805.e1–805–7. doi: 10.1016/j.jamcollsurg.2010.02.045.
  16. 16.
    Keam B, Im S-A, Kim H-J, et al. Clinical significance of axillary nodal ratio in stage II/III breast cancer treated with neoadjuvant chemotherapy. Breast Cancer Res Treat. 2009;116:153–60. doi: 10.1007/s10549-008-0160-9.CrossRefPubMedGoogle Scholar
  17. 17.
    Wu S-G, Li Q, Zhou J, et al. Using the lymph node ratio to evaluate the prognosis of stage II/III breast cancer patients who received neoadjuvant chemotherapy and mastectomy. Cancer Res Treat. 2015;47:757–64. doi: 10.4143/crt.2014.039.CrossRefPubMedGoogle Scholar
  18. 18.
    Jayasinghe UW, Pathmanathan N, Elder E, Boyages J. Prognostic value of the lymph node ratio for lymph-node-positive breast cancer—is it just a denominator problem? Springerplus. 2015;4:121. doi: 10.1186/s40064-015-0865-2.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Vinh-Hung V, Cserni G, Burzykowski T, van de Steene J, Voordeckers M, Storme G. Effect of the number of uninvolved nodes on survival in early breast cancer. Oncol Rep. 2003;10:363–8.PubMedGoogle Scholar
  20. 20.
    Axelsson CK, Mouridsen HT, Zedeler K. Axillary dissection of level I and II lymph nodes is important in breast cancer classification. The Danish Breast Cancer Cooperative Group (DBCG). Eur J Cancer. 1992;28A:1415–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Karlsson P, Cole BF, Price KN, et al. The role of the number of uninvolved lymph nodes in predicting locoregional recurrence in breast cancer. J Clin Oncol. 2007;25:2019–26. doi: 10.1200/JCO.2006.09.8152.CrossRefPubMedGoogle Scholar
  22. 22.
    Olaya W, Wong J, Wong J, Morgan J, Kazanjian K, Lum S. When is a lymph node dissection a lymph node dissection? The number of lymph nodes resected in sentinel and axillary lymph node dissections. Ann Surg Oncol. 2013;20:627–32. doi: 10.1245/s10434-012-2642-6.CrossRefPubMedGoogle Scholar
  23. 23.
    Fisher B, Slack NH. Number of lymph nodes examined and the prognosis of breast carcinoma. Surg Gynecol Obstet. 1970;131:79–88.PubMedGoogle Scholar
  24. 24.
    Swisher SK, Vila J, Tucker SL, et al. Locoregional control according to breast cancer subtype and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast-conserving therapy. Ann Surg Oncol. 2016;23:749–56. doi: 10.1245/s10434-015-4921-5.CrossRefPubMedGoogle Scholar
  25. 25.
    de Azambuja E, Holmes AP, Piccart-Gebhart M, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014;15:1137–46. doi: 10.1016/S1470-2045(14)70320-1.CrossRefPubMedGoogle Scholar
  26. 26.
    Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014;15:640–7. doi: 10.1016/S1470-2045(14)70080-4.CrossRefPubMedGoogle Scholar
  27. 27.
    Vinh-Hung V, Burzykowski T, Cserni G, Voordeckers M, van de Steene J, Storme G. Functional form of the effect of the numbers of axillary nodes on survival in early breast cancer. Int J Oncol. 2003;22:697–704.PubMedGoogle Scholar
  28. 28.
    Tausch C, Taucher S, Dubsky P, et al. Prognostic value of number of removed lymph nodes, number of involved lymph nodes, and lymph node ratio in 7502 breast cancer patients enrolled onto trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG). Ann Surg Oncol. 2012;19:1808–17. doi: 10.1245/s10434-011-2189-y.CrossRefPubMedGoogle Scholar
  29. 29.
    Liao GS, Chou YC, Hsu HM, Dai MS, Yu JC. The prognostic value of lymph node status among breast cancer subtypes. Am J Surg. 2015;209:717–24.CrossRefPubMedGoogle Scholar
  30. 30.
    Saxena N, Hartman M, Aziz R, et al. Prognostic value of axillary lymph node status after neoadjuvant chemotherapy. Results from a multicentre study. Eur J Cancer. 2011;47:1186–92. doi: 10.1016/j.ejca.2010.12.009.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • Jacqueline Tsai
    • 1
  • Danielle Bertoni
    • 1
  • Tina Hernandez-Boussard
    • 1
  • Melinda L. Telli
    • 2
  • Irene L. Wapnir
    • 1
  1. 1.Department of SurgeryStanford University School of MedicineStanfordUSA
  2. 2.Department of MedicineStanford University School of MedicineStanfordUSA

Personalised recommendations