Skip to main content

Advertisement

SpringerLink
Log in

Clinical significance of axillary nodal ratio in stage II/III breast cancer treated with neoadjuvant chemotherapy

  • Clinical Trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose Neoadjuvant chemotherapy may modify the yield of involved axillary lymph nodes. The purpose of this study was to identify the clinical significance of the involved nodal ratios in patients with stage II/III breast cancer treated with neoadjuvant chemotherapy. Methods Two hundred and five stage II and III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this prospective study. The patients received three cycles of neoadjuvant chemotherapy followed by curative surgery, either breast-conserving surgery or mastectomy with axillary lymph node dissection, and received three additional cycles of docetaxel/doxorubicin chemotherapy as adjuvant. Adjuvant radiotherapy and hormonal therapy were given after adjuvant chemotherapy when indicated. Results The median follow-up duration was 28.9 months. The overall response rate (RR) for neoadjuvant chemotherapy was 77.6%. The mean nodal ratio was 0.29 (range, 0–1.0; nodal ratio ≤0.25, 121 [59.0%] vs. >0.25, 84 [41.0%]). Relapse free survival (RFS) of the patients who had a nodal ratio >0.25 was significantly shorter (Hazard Ratio (HR) = 2.701, P = 0.001). A nodal ratio >0.25 was also associated with a shorter overall survival (OS) (HR = 4.109, P = 0.006). However, RFS and OS were not different according to the absolute number of involved nodes (ANIN) (P = 0.166, P = 0.248, respectively). In multivariate analysis, the nodal ratio was an independent prognostic factor for RFS and OS (HR = 4.246, P < 0.001; HR = 7.764, P < 0.001). Conclusion Axillary nodal ratios have an independent prognostic value in stage II/III breast cancer treated with neoadjuvant chemotherapy. Nodal ratio might be a useful tool to identify the patients at high risk of relapse in the neoadjuvant setting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kaufmann M, von Minckwitz G, Smith R et al (2003) International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol 21(13):2600–2608. doi:10.1200/JCO.2003.01.136

    Article  PubMed  Google Scholar 

  2. Estevez LG, Gradishar WJ (2004) Evidence-based use of neoadjuvant taxane in operable and inoperable breast cancer. Clin Cancer Res 10(10):3249–3261. doi:10.1158/1078-0432.CCR-03-0133

    Article  PubMed  CAS  Google Scholar 

  3. Shimizu C, Ando M, Kouno T, Katsumata N, Fujiwara Y et al (2007) Current trends and controversies over pre-operative chemotherapy for women with operable breast cancer. Jpn J Clin Oncol 37(1):1–8. doi:10.1093/jjco/hyl122

    Article  PubMed  Google Scholar 

  4. Fitzgibbons PL, Page DL, Weaver D et al (2000) Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 124(7):966–978

    PubMed  CAS  Google Scholar 

  5. Atkinson EN, Brown BW, Montague ED (1986) Tumor volume, nodal status, and metastasis in breast cancer in women. J Natl Cancer Inst 76(2):171–178

    PubMed  CAS  Google Scholar 

  6. 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. doi :10.1002/1097-0142(19890101)63:1<181::AID-CNCR2820630129>3.0.CO;2-H

    Article  PubMed  CAS  Google Scholar 

  7. Gray RJ (1992) Flexible methods for analyzing survival data using splines, with application to breast cancer prognosis. J Am Stat Assoc 87:942–951. doi:10.2307/2290630

    Article  Google Scholar 

  8. Hilsenbeck SG, Ravdin PM, de Moor CA et al (1998) Time-dependence of hazard ratios for prognostic factors in primary breast cancer. Breast Cancer Res Treat 52(1–3):227–237. doi:10.1023/A:1006133418245

    Article  PubMed  CAS  Google Scholar 

  9. Sauerbrei W, Royston P, Bojar H et al (1999) Modelling the effects of standard prognostic factors in node positive breast cancer. German Breast Cancer Study Group (GBSG). Br J Cancer 79(11–12):1752–1760. doi:10.1038/sj.bjc.6690279

    Article  PubMed  CAS  Google Scholar 

  10. Greene FL, Page DL, Fleming ID et al (2002) AJCC cancer staging manual, 6th edn. Springer, New York

    Google Scholar 

  11. Woodward WA, Vinh-Hung V, Ueno NT et al (2006) Prognostic value of nodal ratios in node-positive breast cancer. J Clin Oncol 24(18):2910–2916. doi:10.1200/JCO.2005.03.1526

    Article  PubMed  Google Scholar 

  12. Truong PT, Berthelet E, Lee J et al (2005) Prognostic significance of the percentage of positive/dissected axillary nodes in breast cancer relapse and survival in patients with 1–3 positive axillary nodes. Cancer 103(10):2006–2014. doi:10.1002/cncr.20969

    Article  PubMed  Google Scholar 

  13. Vinh-Hung V, Verschraegen C, Promish DI et al (2004) Ratios of involved nodes in early breast cancer. Breast Cancer Res 6(6):R680–R688. doi:10.1186/bcr934

    Article  PubMed  Google Scholar 

  14. van der Wal BC, Butzelaar RM, van der Meij S et al (2002) 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 28(5):481–489. doi:10.1053/ejso.2002.1239

    Article  PubMed  Google Scholar 

  15. Voordeckers M, Vinh-Hung V, Van de Steene J et al (2004) The lymph node ratio as prognostic factor in node-positive breast cancer. Radiother Oncol 70(3):225–230. doi:10.1016/j.radonc.2003.10.015

    Article  PubMed  Google Scholar 

  16. Knoop AS, Bentzen SM, Nielsen MM et al (2001) Value of epidermal growth factor receptor, HER2, p53, and steroid receptors in predicting the efficacy of tamoxifen in high-risk postmenopausal breast cancer patients. J Clin Oncol 19(14):3376–3384

    PubMed  CAS  Google Scholar 

  17. Tai P, Joseph K, Sadikov E et al (2007) Nodal ratios in node-positive breast cancer—long-term study to clarify discrepancy of role of supraclavicular and axillary regional radiotherapy. Int J Radiat Oncol Biol Phys 68(3):662–666. doi:10.1016/j.ijrobp.2007.01.057

    PubMed  Google Scholar 

  18. Baslaim MM, Al Malik OA, Al Sobhi SS et al (2002) Decreased axillary lymph node retrieval in patients after neoadjuvant chemotherapy. Am J Surg 184(4):299–301. doi:10.1016/S0002-9610(02)00959-5

    Article  PubMed  Google Scholar 

  19. Keam B, Im SA, Kim HJ et al (2007) Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer. BMC Cancer 7(1):203–213. doi:10.1186/1471-2407-7-203

    Article  PubMed  Google Scholar 

  20. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216. doi:10.1093/jnci/92.3.205

    Article  PubMed  CAS  Google Scholar 

  21. Han S, Kim SB, Kang SS et al (2006) A phase II study of neoadjuvant docetaxel plus doxorubicin (KBCS-01) in stage II, III breast cancer. Breast Cancer Res Treat 98(1):57–61. doi:10.1007/s10549-005-9131-6

    Article  PubMed  CAS  Google Scholar 

  22. Recht A, Edge SB, Solin LJ et al (2001) Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 19(5):1539–1569

    PubMed  CAS  Google Scholar 

  23. Lee KH, Im SA, Oh DY et al (2007) Prognostic significance of bcl-2 expression in stage III breast cancer patients who had received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy. BMC Cancer 12(7):63–71. doi:10.1186/1471-2407-7-63

    Article  Google Scholar 

  24. Vinh-Hung V, Vlastos G, Fioretta G et al (2007) Nodal ratios as an alternative to pN-staging in node-positive breast cancer: a validation study. Breast Cancer Res Treat 106(Suppl 1):S215 (abst 5027)

    Google Scholar 

  25. Martinez-Trufero J, Artal-Cortes A, Zorrilla M et al (2001) New distinctive features on the study of prognostic factors in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (NAC). Proc Am Soc Clin Oncol 20 (abst 3069)

  26. Schmoor C, Sauerbrei W, Bastert G et al (2001) Long-term prognosis of breast cancer patients with 10 or more positive lymph nodes treated with CMF. Eur J Cancer 37(9):1123–1131. doi:10.1016/S0959-8049(01)00090-9

    Article  PubMed  CAS  Google Scholar 

  27. Somner JE, Dixon JM, Thomas JS (2004) Node retrieval in axillary lymph node dissections: recommendations for minimum numbers to be confident about node negative status. J Clin Pathol 57(8):845–848. doi:10.1136/jcp.2003.015560

    Article  PubMed  CAS  Google Scholar 

  28. Schaapveld M, Otter R, de Vries EG et al (2004) Variability in axillary lymph node dissection for breast cancer. J Surg Oncol 87(1):4–12. doi:10.1002/jso.20061

    Article  PubMed  Google Scholar 

  29. Graversen HP, Blichert-Toft M, Andersen JA et al (1988) Breast cancer: risk of axillary recurrence in node-negative patients following partial dissection of the axilla. Eur J Surg Oncol 14(5):407–412

    PubMed  CAS  Google Scholar 

  30. Fowble B, Solin LJ, Schultz DJ et al (1989) Frequency, sites of relapse, and outcome of regional node failures following conservative surgery and radiation for early breast cancer. Int J Radiat Oncol Biol Phys 17(4):703–710

    PubMed  CAS  Google Scholar 

  31. Fisher B, Wolmark N, Bauer M et al (1981) The accuracy of clinical nodal staging and of limited axillary dissection as a determinant of histologic nodal status in carcinoma of the breast. Surg Gynecol Obstet 152(6):765–772

    PubMed  CAS  Google Scholar 

  32. Rostgaard K, Mouridsen HT, Vaeth M et al (2001) A modified Nottingham prognostic index for breast cancer patients diagnosed in Denmark 1978–1994. Acta Oncol 40(7):838–843. doi:10.1080/02841860152703463

    Article  PubMed  CAS  Google Scholar 

  33. Pierga JY, Mouret E, Diéras V, Laurence V, Beuzeboc P, Dorval T, Palangié T, Jouve M, Vincent-Salomon A, Scholl S, Extra JM, Asselain B, Pouillart P et al (2000) Prognostic value of persistent node involvement after neoadjuvant chemotherapy in patients with operable breast cancer. Br J Cancer 83(11):1480–1487. doi:10.1054/bjoc.2000.1461

    Article  PubMed  CAS  Google Scholar 

  34. Hennessy BT, Hortobagyi GN, Rouzier R et al (2005) Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy. J Clin Oncol 23(36):9304–9311. doi:10.1200/JCO.2005.02.5023

    Article  PubMed  Google Scholar 

  35. Buchholz TA, Tucker SL, Masullo L et al (2002) Predictors of local-regional recurrence after neoadjuvant chemotherapy and mastectomy without radiation. J Clin Oncol 20(1):17–23. doi:10.1200/JCO.20.1.17

    Article  PubMed  CAS  Google Scholar 

  36. Kuerer HM, Sahin AA, Hunt KK et al (1999) Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg 230(1):72–78. doi:10.1097/00000658-199907000-00011

    Article  PubMed  CAS  Google Scholar 

  37. Gonzalez-Angulo AM, McGuire SE, Buchholz TA et al (2005) Factors predictive of distant metastases in patients with breast cancer who have a pathologic complete response after neoadjuvant chemotherapy. J Clin Oncol 23(28):7098–7104. doi:10.1200/JCO.2005.11.124

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a Korean Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2006-531-E00034), a grant from the Seoul National University Hospital Research Fund (05-800-20050148). We would like to thank our clinical research nurse Kyung-Hee Lee for her assistance of clinical trial. We also thank Dr. Cunningham, English editor of BioMed Proofreading for his assistance. This study was presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 30th–June 3rd, 2008.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, Republic of Korea

    Bhumsuk Keam, Seock-Ah Im, Hee-Jun Kim, Do-Youn Oh, Jee Hyun Kim, Se-Hoon Lee, Dong-Wan Kim, Tae-You Kim, Dae Seog Heo & Yung-Jue Bang

  2. Cancer Research Institute, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea

    Seock-Ah Im, Do-Youn Oh, Jee Hyun Kim, Se-Hoon Lee, Eui Kyu Chie, Wonshik Han, Dong-Wan Kim, Tae-You Kim, In Ae Park, Dong-Young Noh, Dae Seog Heo, Sung Whan Ha & Yung-Jue Bang

  3. Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea

    Eui Kyu Chie & Sung Whan Ha

  4. Department of Surgery, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea

    Wonshik Han & Dong-Young Noh

  5. Department of Radiology, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea

    Nariya Cho & Woo Kyung Moon

  6. Department of Pathology, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea

    In Ae Park

Authors
  1. Bhumsuk Keam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seock-Ah Im
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hee-Jun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Do-Youn Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jee Hyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Se-Hoon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eui Kyu Chie
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wonshik Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dong-Wan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nariya Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Woo Kyung Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Tae-You Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. In Ae Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Dong-Young Noh
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Dae Seog Heo
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Sung Whan Ha
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Yung-Jue Bang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seock-Ah Im.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keam, B., Im, SA., Kim, HJ. et al. Clinical significance of axillary nodal ratio in stage II/III breast cancer treated with neoadjuvant chemotherapy. Breast Cancer Res Treat 116, 153–160 (2009). https://doi.org/10.1007/s10549-008-0160-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-008-0160-9

Keywords

Search

Navigation