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Breast Cancer Research and Treatment

, Volume 139, Issue 1, pp 87–93 | Cite as

Intraoperative molecular analysis of total tumor load in sentinel lymph node: a new predictor of axillary status in early breast cancer patients

  • Vicente Peg
  • Martín Espinosa-Bravo
  • Begoña Vieites
  • Felip Vilardell
  • José R. Antúnez
  • Magdalena Sancho de Salas
  • Julio J. Delgado-Sánchez
  • Willy Pinto
  • Francisco Gozalbo
  • Anna Petit
  • Irene Sansano
  • María del Mar Téllez
  • Isabel T. Rubio
Clinical Trial

Abstract

Objective To assess the intraoperative positive sentinel lymph node (SLN) total tumor load (TTL, defined as the amount of CK19 mRNA copies [copies/μL] in all positive SLNs) obtained by one-step nucleic acid amplification (OSNA) and to determine whether it is predictive of non-SLNs involvement. Summary background data The OSNA assay (Sysmex Corporation, Kobe, Japan) is a new diagnostic technique that uses molecular biological techniques to analyze SLN that has been validated as an accurate method for detection of positive SLN. Although the American College of Surgeons Oncology Group Z0011 trial has defined a select cohort of patients in whom a completion axillary lymph node dissection (cALND) may be safely omitted, there are a still a number of patients where prediction of non-SLN metastasis may be helpful for cALND decision making. Multiple studies suggest that specific pathologic characteristics of the primary tumor and the SLN metastases are associated with an increased likelihood of additional positive non-SLN. Methods This is a retrospective multicentric cohort study of 697 patients with cT1-3N0 breast cancer, who had had intraoperative SLN evaluation by OSNA assay with a cALND. TTL is defined as the amount of CK19 mRNA copies number in all positives SLN (copies/μL). Results Univariate logistic regression showed that, in addition to TTL (p < 0.001), the number of affected SLNs (p < 0.001), tumor size (p < 0.001), HER2 status (p = 0.007), and lymphovascular invasion (LVI, p < 0.001) were predictive of ALND status. The multivariate logistic regression analysis showed that TTL is an independent predictor of metastatic non-SLNs, after adjusting for the tumor size, HER2 status, LVI and, in particular, the number of affected SLNs. Conclusions TTL by OSNA is a newly standardized and automated tool that predicts axillary node status better and independently of the number of affected SLNs and the type of surgery. This value can then help clinicians to personalize surgical treatment. Prospective studies will be carried out to determine the clinical impact of this variable in the management of patients.

Keywords

Breast sentinel lymph node OSNA Total tumor load 

Notes

Acknowledgments

This study was supported by a Grant from the Sysmex España S.L. The sponsor had no role in the study design, analysis, or interpretation of the data.

Conflict of interest

All authors declare no conflict of interest.

Supplementary material

10549_2013_2524_MOESM1_ESM.docx (86 kb)
Supplementary material 1 (DOCX 86 kb)

References

  1. 1.
    Weaver DL, Ashikaga T, Krag DN, Skelly JM, Anderson SJ, Harlow SP, Julian TB, Mamounas EP, Wolmark N (2011) Effect of occult metastases on survival in node-negative breast cancer. N Engl J Med 364(5):412–421PubMedCrossRefGoogle Scholar
  2. 2.
    Fisher B, Bauer M, Wickerham DL, Redmond CK, Fisher ER, Cruz AB, Foster R, Gardner B, Lerner H, Margolese R et al (1983) Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer 52(9):1551–1557PubMedCrossRefGoogle Scholar
  3. 3.
    Michaelson JS, Silverstein M, Sgroi D, Cheongsiatmoy JA, Taghian A, Powell S, Hughes K, Comegno A, Tanabe KK, Smith B (2003) The effect of tumor size and lymph node status on breast carcinoma lethality. Cancer 98(10):2133–2143PubMedCrossRefGoogle Scholar
  4. 4.
    Lyman GH, Giuliano AE, Somerfield MR, Benson AB III, Bodurka DC, Burstein HJ, Cochran AJ, Cody HS III, Edge SB, Galper S et al (2005) American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 23(30):7703–7720PubMedCrossRefGoogle Scholar
  5. 5.
    Weaver DL (2010) Pathology evaluation of sentinel lymph nodes in breast cancer: protocol recommendations and rationale. Mod Pathol 23(Suppl 2):S26–S32PubMedCrossRefGoogle Scholar
  6. 6.
    Cserni G, Amendoeira I, Apostolikas N, Bellocq JP, Bianchi S, Bussolati G, Boecker W, Borisch B, Connolly CE, Decker T et al (2003) Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines. Eur J Cancer 39(12):1654–1667PubMedCrossRefGoogle Scholar
  7. 7.
    Tsujimoto M, Nakabayashi K, Yoshidome K, Kaneko T, Iwase T, Akiyama F, Kato Y, Tsuda H, Ueda S, Sato K et al (2007) One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res 13(16):4807–4816PubMedCrossRefGoogle Scholar
  8. 8.
    Tamaki Y, Akiyama F, Iwase T, Kaneko T, Tsuda H, Sato K, Ueda S, Mano M, Masuda N, Takeda M et al (2009) Molecular detection of lymph node metastases in breast cancer patients: results of a multicenter trial using the one-step nucleic acid amplification assay. Clin Cancer Res 15(8):2879–2884PubMedCrossRefGoogle Scholar
  9. 9.
    Visser M, Jiwa M, Horstman A, Brink AA, Pol RP, van Diest P, Snijders PJ, Meijer CJ (2008) Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer. Int J Cancer 122(11):2562–2567PubMedCrossRefGoogle Scholar
  10. 10.
    Tamaki Y, Sato N, Homma K, Takabatake D, Nishimura R, Tsujimoto M, Yoshidome K, Tsuda H, Kinoshita T, Kato H et al (2012) Routine clinical use of the one-step nucleic acid amplification assay for detection of sentinel lymph node metastases in breast cancer patients: results of a multicenter study in Japan. Cancer 118(14):3477–3483PubMedCrossRefGoogle Scholar
  11. 11.
    Snook KL, Layer GT, Jackson PA, de Vries CS, Shousha S, Sinnett HD, Nigar E, Singhal H, Chia Y, Cunnick G et al (2011) Multicentre evaluation of intraoperative molecular analysis of sentinel lymph nodes in breast carcinoma. Br J Surg 98(4):527–535PubMedCrossRefGoogle Scholar
  12. 12.
    Feldman S, Krishnamurthy S, Gillanders W, Gittleman M, Beitsch PD, Young PR, Streck CJ, Whitworth PW, Levine EA, Boolbol S et al (2011) A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes. Cancer 117(12):2599–2607PubMedCrossRefGoogle Scholar
  13. 13.
    Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, McCall LM, Morrow M (2011) Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 305(6):569–575PubMedCrossRefGoogle Scholar
  14. 14.
    Caudle AS, Hunt KK, Tucker SL, Hoffman K, Gainer SM, Lucci A, Kuerer HM, Meric-Bernstam F, Shah R, Babiera GV et al (2012) American College of Surgeons Oncology Group (ACOSOG) Z0011: impact on surgeon practice patterns. Ann Surg Oncol 19(10):3144–3151PubMedCrossRefGoogle Scholar
  15. 15.
    Gainer SM, Hunt KK, Beitsch P, Caudle AS, Mittendorf EA, Lucci A (2012) Changing Behavior in Clinical Practice in Response to the ACOSOG Z0011 Trial: a survey of the American Society of Breast Surgeons. Ann Surg Oncol 19(10):3152–3158PubMedCrossRefGoogle Scholar
  16. 16.
    van la Parra RF, Peer PG, Ernst MF, Bosscha K (2011) Meta-analysis of predictive factors for non-sentinel lymph node metastases in breast cancer patients with a positive SLN. Eur J Surg Oncol 37(4):290–299CrossRefGoogle Scholar
  17. 17.
    Van Zee KJ, Manasseh DM, Bevilacqua JL, Boolbol SK, Fey JV, Tan LK, Borgen PI, Cody HS III, Kattan MW (2003) A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy. Ann Surg Oncol 10(10):1140–1151PubMedCrossRefGoogle Scholar
  18. 18.
    Houvenaeghel G, Nos C, Giard S, Mignotte H, Esterni B, Jacquemier J, Buttarelli M, Classe JM, Cohen M, Rouanet P et al (2009) A nomogram predictive of non-sentinel lymph node involvement in breast cancer patients with a sentinel lymph node micrometastasis. Eur J Surg Oncol 35(7):690–695PubMedCrossRefGoogle Scholar
  19. 19.
    Mittendorf EA, Hunt KK, Boughey JC, Bassett R, Degnim AC, Harrell R, Yi M, Meric-Bernstam F, Ross MI, Babiera GV et al (2012) Incorporation of sentinel lymph node metastasis size into a nomogram predicting nonsentinel lymph node involvement in breast cancer patients with a positive sentinel lymph node. Ann Surg 255(1):109–115PubMedCrossRefGoogle Scholar
  20. 20.
    Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M et al (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28(16):2784–2795PubMedCrossRefGoogle Scholar
  21. 21.
    Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A et al (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25(1):118–145PubMedCrossRefGoogle Scholar
  22. 22.
    Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, Ellis M, Henry NL, Hugh JC, Lively T et al (2011) Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst 103(22):1656–1664PubMedCrossRefGoogle Scholar
  23. 23.
    Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, Members P (2011) Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22(8):1736–1747PubMedCrossRefGoogle Scholar
  24. 24.
    Rubio IT, Aznar F, Lirola J, Peg V, Xercavins J (2010) Intraoperative assessment of sentinel lymph nodes after neoadjuvant chemotherapy in patients with breast cancer. Ann Surg Oncol 17(1):235–239PubMedCrossRefGoogle Scholar
  25. 25.
    Edge SB, Byrd DR, Compton CC, Fritz AG et al (2010) AJCC cancer staging manual, 7th edn. Springer, New YorkGoogle Scholar
  26. 26.
    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):335–339; discussion 340Google Scholar
  27. 27.
    Cserni G, Amendoeira I, Apostolikas N, Bellocq JP, Bianchi S, Boecker W, Borisch B, Connolly CE, Decker T, Dervan P et al (2004) Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology. J Clin Pathol 57(7):695–701PubMedCrossRefGoogle Scholar
  28. 28.
    Cserni G (2012) Intraoperative analysis of sentinel lymph nodes in breast cancer by one-step nucleic acid amplification. J Clin Pathol 65(3):193–199PubMedCrossRefGoogle Scholar
  29. 29.
    Pepels MJ, de Boer M, Bult P, van Dijck JA, van Deurzen CH, Menke-Pluymers MB, van Diest PJ, Borm GF, Tjan-Heijnen VC (2012) Regional recurrence in breast cancer patients with sentinel node micrometastases and isolated tumor cells. Ann Surg 255(1):116–121PubMedCrossRefGoogle Scholar
  30. 30.
    Meretoja TJ, Leidenius MH, Heikkilä PS, Boross G, Sejben I, Regitnig P, Luschin-Ebengreuth G, Zgajnar J, Perhavec A, Gazic B et al (2012) International multicenter tool to predict the risk of nonsentinel node metastases in breast cancer. J Natl Cancer Inst 104(24):1888–1896. doi: 10.1093/jnci/djs455 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Vicente Peg
    • 1
    • 11
  • Martín Espinosa-Bravo
    • 12
  • Begoña Vieites
    • 2
  • Felip Vilardell
    • 3
  • José R. Antúnez
    • 4
  • Magdalena Sancho de Salas
    • 5
  • Julio J. Delgado-Sánchez
    • 6
  • Willy Pinto
    • 7
  • Francisco Gozalbo
    • 8
  • Anna Petit
    • 9
  • Irene Sansano
    • 1
    • 11
  • María del Mar Téllez
    • 10
  • Isabel T. Rubio
    • 12
  1. 1.Department of PathologyVall d’Hebron University HospitalBarcelonaSpain
  2. 2.Department of PathologyHospital Virgen del RocíoSevilleSpain
  3. 3.Department of PathologyHospital Arnau de VilanovaLéridaSpain
  4. 4.Department of PathologyComplejo Hospitalario Universitario de Santiago de CompostelaSantiago de CompostelaSpain
  5. 5.Department of PathologyHospital Clínico de SalamancaSalamancaSpain
  6. 6.Department of PathologyHospital 12 de OctubreMadridSpain
  7. 7.Department of PathologyHospital Dr. NegrínGran CanarySpain
  8. 8.Instituto Valenciano de OncologíaValenciaSpain
  9. 9.Department of PathologyHospital de BellvitgeBarcelonaSpain
  10. 10.SOLTI Breast Cancer Research GroupBarcelonaSpain
  11. 11.Department of Morphological SciencesUniversitat Autònoma de BarcelonaBarcelonaSpain
  12. 12.Breast Cancer CenterVall d’Hebron University HospitalBarcelonaSpain

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