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Published in: Annals of Surgical Oncology 10/2016

01-10-2016 | Breast Oncology

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

Authors: Jacqueline Tsai, MD, Danielle Bertoni, MD, Tina Hernandez-Boussard, PhD, Melinda L. Telli, MD, Irene L. Wapnir, MD

Published in: Annals of Surgical Oncology | Issue 10/2016

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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.
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Literature
1.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
2.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference Greene FL, Balch CM, Fleming ID, et al. Cancer AJCO. AJCC cancer staging handbook. New York: Springer; 2002. Greene FL, Balch CM, Fleming ID, et al. Cancer AJCO. AJCC cancer staging handbook. New York: Springer; 2002.
6.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
7.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
8.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
10.
go back to reference 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. 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.
13.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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. 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.
17.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
19.
go back to reference 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.PubMed 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.PubMed
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
22.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
23.
go back to reference Fisher B, Slack NH. Number of lymph nodes examined and the prognosis of breast carcinoma. Surg Gynecol Obstet. 1970;131:79–88.PubMed Fisher B, Slack NH. Number of lymph nodes examined and the prognosis of breast carcinoma. Surg Gynecol Obstet. 1970;131:79–88.PubMed
24.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
25.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
26.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
27.
go back to reference 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.PubMed 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.PubMed
28.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
29.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
Lymph Node Ratio Analysis After Neoadjuvant Chemotherapy is Prognostic in Hormone Receptor-Positive and Triple-Negative Breast Cancer
Authors
Jacqueline Tsai, MD
Danielle Bertoni, MD
Tina Hernandez-Boussard, PhD
Melinda L. Telli, MD
Irene L. Wapnir, MD
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 10/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5319-8

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