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Breast Cancer Research and Treatment

, Volume 116, Issue 1, pp 153–160 | Cite as

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

  • Bhumsuk Keam
  • Seock-Ah ImEmail author
  • Hee-Jun Kim
  • Do-Youn Oh
  • Jee Hyun Kim
  • Se-Hoon Lee
  • Eui Kyu Chie
  • Wonshik Han
  • Dong-Wan Kim
  • Nariya Cho
  • Woo Kyung Moon
  • Tae-You Kim
  • In Ae Park
  • Dong-Young Noh
  • Dae Seog Heo
  • Sung Whan Ha
  • Yung-Jue Bang
Clinical Trial

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.

Keywords

Nodal ratio Neoadjuvant chemotherapy Prognosis Breast cancer Nodal stage 

Notes

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.

References

  1. 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 PubMedCrossRefGoogle Scholar
  2. 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 PubMedCrossRefGoogle Scholar
  3. 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 PubMedCrossRefGoogle Scholar
  4. 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):966–978PubMedGoogle Scholar
  5. 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):171–178PubMedGoogle Scholar
  6. 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-HPubMedCrossRefGoogle Scholar
  7. 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 CrossRefGoogle Scholar
  8. 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 PubMedCrossRefGoogle Scholar
  9. 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 PubMedCrossRefGoogle Scholar
  10. 10.
    Greene FL, Page DL, Fleming ID et al (2002) AJCC cancer staging manual, 6th edn. Springer, New YorkGoogle Scholar
  11. 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 PubMedCrossRefGoogle Scholar
  12. 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 PubMedCrossRefGoogle Scholar
  13. 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 PubMedCrossRefGoogle Scholar
  14. 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 PubMedCrossRefGoogle Scholar
  15. 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 PubMedCrossRefGoogle Scholar
  16. 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):3376–3384PubMedGoogle Scholar
  17. 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 PubMedGoogle Scholar
  18. 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 PubMedCrossRefGoogle Scholar
  19. 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 PubMedCrossRefGoogle Scholar
  20. 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 PubMedCrossRefGoogle Scholar
  21. 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 PubMedCrossRefGoogle Scholar
  22. 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):1539–1569PubMedGoogle Scholar
  23. 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 CrossRefGoogle Scholar
  24. 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. 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)Google Scholar
  26. 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 PubMedCrossRefGoogle Scholar
  27. 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 PubMedCrossRefGoogle Scholar
  28. 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 PubMedCrossRefGoogle Scholar
  29. 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):407–412PubMedGoogle Scholar
  30. 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):703–710PubMedGoogle Scholar
  31. 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):765–772PubMedGoogle Scholar
  32. 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 PubMedCrossRefGoogle Scholar
  33. 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 PubMedCrossRefGoogle Scholar
  34. 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 PubMedCrossRefGoogle Scholar
  35. 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 PubMedCrossRefGoogle Scholar
  36. 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 PubMedCrossRefGoogle Scholar
  37. 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 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Bhumsuk Keam
    • 1
  • Seock-Ah Im
    • 1
    • 2
    Email author
  • Hee-Jun Kim
    • 1
  • Do-Youn Oh
    • 1
    • 2
  • Jee Hyun Kim
    • 1
    • 2
  • Se-Hoon Lee
    • 1
    • 2
  • Eui Kyu Chie
    • 2
    • 3
  • Wonshik Han
    • 2
    • 4
  • Dong-Wan Kim
    • 1
    • 2
  • Nariya Cho
    • 5
  • Woo Kyung Moon
    • 5
  • Tae-You Kim
    • 1
    • 2
  • In Ae Park
    • 2
    • 6
  • Dong-Young Noh
    • 2
    • 4
  • Dae Seog Heo
    • 1
    • 2
  • Sung Whan Ha
    • 2
    • 3
  • Yung-Jue Bang
    • 1
    • 2
  1. 1.Department of Internal MedicineSeoul National University College of MedicineSeoulRepublic of Korea
  2. 2.Cancer Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea
  3. 3.Department of Radiation OncologySeoul National University College of MedicineSeoulRepublic of Korea
  4. 4.Department of SurgerySeoul National University College of MedicineSeoulRepublic of Korea
  5. 5.Department of RadiologySeoul National University College of MedicineSeoulRepublic of Korea
  6. 6.Department of PathologySeoul National University College of MedicineSeoulRepublic of Korea

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