CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2022; 82(06): 610-618
DOI: 10.1055/a-1749-5226
GebFra Science
Original Article

Evaluation of Intraoperative Frozen Section Analysis with Final Histopathology Results for Sentinel Lymph Node Biopsy: Z0011 Criteria Eligible Versus Ineligible Breast Cancer Patients

Bedeutung von intraoperativer Gefrierschnittanalyse und histopathologischen Ergebnissen von Wächterlymphknotenbiopsien: Vergleich von Z0011-Studie-geeigneten mit ungeeigneten Brustkrebspatientinnen
Florian Reinhardt
1   Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Anna Fiedler
1   Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Felix Borgmeier
1   Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Petra Reinecke
2   Institute of Pathology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Irene Esposito
2   Institute of Pathology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Katalin Mattes-György
3   Department of Nuclear Medicine, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Mardjan Dabir
3   Department of Nuclear Medicine, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Verena Friebe
1   Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Natalia Krawczyk
1   Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Thomas Kaleta
1   Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Jürgen Hoffmann
1   Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Eugen Ruckhäberle
1   Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Tanja Fehm
1   Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Katrin S. Roth
4   Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany
5   Department of Diagnostic and Interventional Radiology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
,
Svjetlana Mohrmann
1   Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
› Author Affiliations
› Further Information
   Permissions and Reprints

Abstract

Background Intraoperative frozen section analysis (FSA) of sentinel lymph nodes (SLNs) declined in the post American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial era. However, for those patients who do not meet the ACOSOG Z0011 criteria, FSA continues to be a valuable tool in intraoperative decision-making for axillary lymph node dissection (ALND). The aim of this study was therefore to retrospectively evaluate the benefit and accuracy of FSA of Z0011 criteria eligible versus ineligible patients and identify possible predictive factors for false negative results.

Methods Intraoperative FSA was performed on SLNs of 522 cT1–T3 breast cancer patients between 2008 and 2013. Clinicopathologic characteristics were retrospectively assessed by chart review.

Results Overall FSA sensitivity and specificity was 67.8% and 100%. Sensitivity was generally higher for macrometastasis than for micrometastasis. The Z0011 eligible group showed a sensitivity and specificity of 72.7% and 100% versus 62.1% and 100% in the Z0011 ineligible group. Importantly, subgroup analysis of ≤ 2 versus > 2 positive SLNs of the Z0011 eligible group demonstrated both a 100% specificity and sensitivity. Several clinicopathologic factors were associated with a higher rate of false negative results in the Z0011 ineligible patient group. FSA was beneficial for 22.2% of Z0011 ineligible patients and for only 0.6% of Z0011 eligible patients regarding intraoperative decision-making for ALND.

Conclusions FSA continues to be especially beneficial in the intraoperative assessment of SLNs in the Z0011 ineligible group to prevent second stage ALND. Despite an overall lower FSA sensitivity in the Z0011 eligible patient group, FSA offers in both groups a comparable high sensitivity and diagnostic accuracy for macrometastasis.

Zusammenfassung

Hintergrund Nach der Veröffentlichung der American College of Surgeons Oncology Group Z0011-Studie (ACOSOG Z0011) ist die Analyse der intraoperativen Gefrierschnitte von Wächterlymphknoten zurückgegangen. Aber für Patientinnen, welche die ACOSOG Z0011-Kriterien nicht erfüllen, bleibt die Gefrierschnittanalyse ein wichtiges Instrument für die intraoperative Entscheidungsfindung im Hinblick auf eine Axilladissektion. Ziel dieser Studie war es, eine retrospektive Evaluierung der Vorteile und der diagnostischen Genauigkeit von Gefrierschnittanalysen bei Brustkrebspatientinnen durchzuführen, welche die Kriterien der Z0011-Studie erfüllten oder nicht erfüllten, und dabei mögliche prädiktive Faktoren für falsch negative Ergebnisse festzustellen.

Methoden Zwischen 2008 und 2013 wurde eine intraoperative Gefrierschnittanalyse der Wächterlymphknoten bei 522 cT1–T3-Brustkrebspatientinnen durchgeführt. Die klinisch-pathologischen Merkmale wurden retrospektiv mithilfe der Krankenakten evaluiert.

Ergebnisse Insgesamt betrug die Sensitivität und Spezifität für alle Gefrierschnittanalysen 67,8% bzw. 100%. Generell war die Sensitivität für Makrometastasen höher als für Mikrometastasen. Bei der Gruppe, welche die Kriterien der Z0011-Studie erfüllte, betrugen die Sensitivität und Spezifität 72,7% bzw. 100%, verglichen mit 62,1% bzw. 100% für die Gruppe, welche die Z0011-Kriterien nicht erfüllte. In der Gruppe, welche die Z0011-Kriterien erfüllte, wurde eine Untergruppenanalyse durchgeführt, und die Ergebnisse für ≤ 2 positiven Wächterlymphknoten wurden mit den Ergebnissen für > 2 verglichen. Bei beiden Untergruppen betrugen Spezifität und Sensitivität jeweils 100%. In der Patientinnengruppe, welche die Z0011-Kriterien nicht erfüllte, waren mehrere klinisch-pathologische Faktoren mit einer höheren Rate an falsch positiven Ergebnissen assoziiert. Im Hinblick auf die intraoperative Entscheidungsfindung für eine Axilladissektion brachte die Durchführung einer intraoperativen Gefrierschnittanalyse Vorteile für 22,2% der Patientinnen, welche die Z0011-Kriterien nicht erfüllten, aber nur für 0,6% der Patientinnen, welche die Z0011-Kriterien erfüllten.

Schlussfolgerungen Die Gefrierschnittanalyse ist besonders für die intraoperative Evaluierung von Wächterlymphknoten bei Patientinnen, welche die Z0011-Kriterien nicht erfüllen, vorteilhaft, da dadurch eine Zweitoperation zur Axilladissektion vermieden werden kann. Obwohl die Sensitivität der Gefrierschnittanalyse in der Gruppe, welche die Z0011-Kriterien erfüllte, insgesamt niedriger war, hat die Gefrierschnittanalyse in beiden Gruppen eine vergleichbar hohe Sensitivität und diagnostische Genauigkeit für Makrometastasen.

Key words

breast cancer - sentinel lymph node - frozen section analysis

Schlüsselwörter

Brustkrebs - Wächterlymphknoten - Gefrierschnittanalyse


Publication History

Received: 28 September 2021

Accepted after revision: 24 January 2022

Article published online:
03 June 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Canavese G, Catturich A, Vecchio C. et al. Sentinel node biopsy compared with complete axillary dissection for staging early breast cancer with clinically negative lymph nodes: results of randomized trial. Ann Oncol 2009; 20: 1001-1007 DOI: 10.1093/annonc/mdn746.
    CrossrefPubMedGoogle Scholar
  • 2 Krag DN, Anderson SJ, Julian TB. et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol 2010; 11: 927-933 DOI: 10.1016/S1470-2045(10)70207-2.
    CrossrefPubMedGoogle Scholar
  • 3 Mansel RE, Fallowfield L, Kissin M. et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst 2006; 98: 599-609 DOI: 10.1093/jnci/djj158.
    CrossrefPubMedGoogle Scholar
  • 4 Veronesi U, Paganelli G, Viale G. et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003; 349: 546-553 DOI: 10.1056/NEJMoa012782.
    CrossrefPubMedGoogle Scholar
  • 5 Veronesi U, Viale G, Paganelli G. et al. Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg 2010; 251: 595-600 DOI: 10.1097/SLA.0b013e3181c0e92a.
    CrossrefPubMedGoogle Scholar
  • 6 Zavagno G, De Salvo GL, Scalco G. et al. A Randomized clinical trial on sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer: results of the Sentinella/GIVOM trial. Ann Surg 2008; 247: 207-213 DOI: 10.1097/SLA.0b013e31812e6a73.
    CrossrefPubMedGoogle Scholar
  • 7 Galimberti V, Cole BF, Viale G. et al. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial. Lancet Oncol 2018; 19: 1385-1393 DOI: 10.1016/S1470-2045(18)30380-2.
    CrossrefPubMedGoogle Scholar
  • 8 Giuliano AE, Hunt KK, Ballman KV. et al. Axillary dissection vs. no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 2011; 305: 569-575 DOI: 10.1001/jama.2011.90.
    CrossrefPubMedGoogle Scholar
  • 9 Jorns JM, Kidwell KM. Sentinel Lymph Node Frozen-Section Utilization Declines After Publication of American College of Surgeons Oncology Group Z0011 Trial Results With No Change in Subsequent Surgery for Axillary Lymph Node Dissection. Am J Clin Pathol 2016; 146: 57-66 DOI: 10.1093/ajcp/aqw078.
    CrossrefPubMedGoogle Scholar
  • 10 Weber WP, Barry M, Stempel MM. et al. A 10-year trend analysis of sentinel lymph node frozen section and completion axillary dissection for breast cancer: are these procedures becoming obsolete?. Ann Surg Oncol 2012; 19: 225-232 DOI: 10.1245/s10434-011-1823-z.
    CrossrefPubMedGoogle Scholar
  • 11 Liu LC, Lang JE, Lu Y. et al. Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer patients: a meta-analysis and single-institution experience. Cancer 2011; 117: 250-258 DOI: 10.1002/cncr.25606.
    CrossrefPubMedGoogle Scholar
  • 12 Fillion MM, Glass KE, Hayek J. et al. Healthcare Costs Reduced After Incorporating the Results of the American College of Surgeons Oncology Group Z0011 Trial into Clinical Practice. Breast J 2017; 23: 275-281 DOI: 10.1111/tbj.12728.
    CrossrefPubMedGoogle Scholar
  • 13 Lester SC, Bose S, Chen YY. et al. Protocol for the examination of specimens from patients with invasive carcinoma of the breast. Arch Pathol Lab Med 2009; 133: 1515-1538 DOI: 10.1043/1543-2165-133.10.1515.
    CrossrefPubMedGoogle Scholar
  • 14 Tew K, Irwig L, Matthews A. et al. Meta-analysis of sentinel node imprint cytology in breast cancer. Br J Surg 2005; 92: 1068-1080 DOI: 10.1002/bjs.5139.
    CrossrefPubMedGoogle Scholar
  • 15 Lyman GH, Giuliano AE, Somerfield MR. et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 2005; 23: 7703-7720 DOI: 10.1200/JCO.2005.08.001.
    CrossrefPubMedGoogle Scholar
  • 16 Layfield DM, Agrawal A, Roche H. et al. Intraoperative assessment of sentinel lymph nodes in breast cancer. Br J Surg 2011; 98: 4-17 DOI: 10.1002/bjs.7229.
    CrossrefPubMedGoogle Scholar
  • 17 Veronesi U, Paganelli G, Viale G. et al. Sentinel lymph node biopsy and axillary dissection in breast cancer: results in a large series. J Natl Cancer Inst 1999; 91: 368-373 DOI: 10.1093/jnci/91.4.368.
    CrossrefPubMedGoogle Scholar
  • 18 Cipolla C, Graceffa G, Cabibi D. et al. Current Role of Intraoperative Frozen Section Examination of Sentinel Lymph Node in Early Breast Cancer. Anticancer Res 2020; 40: 1711-1717 DOI: 10.21873/anticanres.14124.
    CrossrefPubMedGoogle Scholar
  • 19 Wada N, Imoto S, Hasebe T. et al. Evaluation of intraoperative frozen section diagnosis of sentinel lymph nodes in breast cancer. Jpn J Clin Oncol 2004; 34: 113-117 DOI: 10.1093/jjco/hyh023.
    CrossrefPubMedGoogle Scholar
  • 20 Lu Q, Tan EY, Ho B. et al. Achieving breast cancer surgery in a single setting with intraoperative frozen section analysis of the sentinel lymph node. Clin Breast Cancer 2013; 13: 140-145 DOI: 10.1016/j.clbc.2012.11.005.
    CrossrefPubMedGoogle Scholar
  • 21 Takei H, Kurosumi M, Yoshida T. et al. Axillary lymph node dissection can be avoided in women with breast cancer with intraoperative, false-negative sentinel lymph node biopsies. Breast Cancer 2010; 17: 9-16 DOI: 10.1007/s12282-009-0154-4.
    CrossrefPubMedGoogle Scholar
  • 22 Qiao G, Cong Y, Zou H. et al. False-negative Frozen Section of Sentinel Lymph Node Biopsy in a Chinese Population with Breast Cancer. Anticancer Res 2016; 36: 1331-1337
    Google Scholar
  • 23 Yoon KH, Park S, Kim JY. et al. Is the frozen section examination for sentinel lymph node necessary in early breast cancer patients?. Ann Surg Treat Res 2019; 97: 49-57 DOI: 10.4174/astr.2019.97.2.49.
    CrossrefPubMedGoogle Scholar
  • 24 Barakat FH, Sulaiman I, Sughayer MA. Reliability of frozen section in breast sentinel lymph node examination. Breast Cancer 2014; 21: 576-582 DOI: 10.1007/s12282-012-0431-5.
    CrossrefPubMedGoogle Scholar
  • 25 Sams SB, Wisell JA. Discordance Between Intraoperative Consultation by Frozen Section and Final Diagnosis. Int J Surg Pathol 2017; 25: 41-50 DOI: 10.1177/1066896916662152.
    CrossrefPubMedGoogle Scholar