Sentinel Node Biopsy Before and/or After Neoadjuvant Chemotherapy in Breast Cancer

October 24, 2019 updated by: Linda Zetterlund, Stockholm South General Hospital
The purpose of this study is to investigate if sentinel lymph node biopsy is a reliable staging tool for breast cancer patients planned for neoadjuvant chemotherapy (=before breast surgery) and if, in that case, it is safe to omit axillary lymph node dissection if the sentinel lymph node is free of metastasis.

Study Overview

Status

Completed

Conditions

Detailed Description

Sentinel lymph node biopsy (SLNB) was introduced in the late 1990´s and has become standard procedure for staging of the axilla in early stage breast cancer associated with significantly less arm morbidity than axillary lymph node dissection (ALND).

Neoadjuvant chemotherapy (NAC) given before breast surgery is indicated for locally advanced breast cancer but is increasingly used for early stage breast cancer with the purpose of downstaging the tumor and thereby possibly enabling breast conserving surgery. Traditionally, the standard axillary staging tool has been ALND although up to 50 per cent of the patients at diagnosis do not have any metastases in their axillary lymph nodes. In addition, NAC can eradicate metastases in the axillary lymph nodes in up to 40 per cent of the patients.

SLNB has therefore been evaluated in the neoadjuvant setting both before and after NAC but is still controversial and the timing debated.

This is a Swedish prospective multi-institutional study without any comparison goup. The comparison is between the findings in the SLNB and the following ALND performed after NAC in all patients.

If the patient is clinically node-negative at diagnosis a SLNB is performed before (without frozen section) and after NAC (substudy I). The reasons for repeating SLNB both before and after NAC are 1) to find out what happens during NAC 2) if it is possible to identify a repeat SLNB and 3) if it is reliable.

If the patient is node-positive at diagnosis (cytologically verified lymph node metastasis) SLNB is performed after NAC together with the breast operation and ALND (substudy II). When SLNB is performed after NAC, the sentinel lymph nodes are also analysed with frozen section in order to validate the method after chemotherapy. Both blue dye and radiolabelled isotope for localisation of the sentinel lymph node is recommended but lymphoscintigraphy is optional.

All consecutive clinically node-negative (or with unclear nodal status after ultrasound and cytology) patients planned for NAC will have oral and written information about the study by the responsible surgeon. After accepting to participate, the patient is asked to sign a written consent. Patients with a cytologically verified lymph node metastasis/es at diagnosis will be informed and asked to participate in substudy II after completion of NAC.

According to the statistical analysis, and with an expected loss of 10 per cent, a sample size of 220 patients is needed in substudy I to show that the false negative rate is less than 10 per cent. If we include 200 patients and 50 per cent are lymph node positive at diagnosis then the estimation of false negative rate will be based on 100 individuals. If we estimate the true false negative rate to be 8 per cent, then the precision with 80 per cent power will be +/- 7 per cent units (2-sided test with 95 per cent confidence interval).

The Central Contact (PI) is responsible for data collection, management and analysis. Each protocol will be sent together with a written consent and copies of all relevant histopathological reports to the PI, who will control for missing or incongruent data and if so, ask the responsible investigator on that institution/hospital to complement the missing data from the patients journal (copies of medical records or histopathological reports).

Study Type

Observational

Enrollment (Actual)

224

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Falun, Sweden, 791 85
        • Falu Lasarett
      • Göteborg, Sweden, 413 45
        • Sahlgrenska Universitetssjukhuset, Sahlgrenska
      • Halmstad, Sweden, 301 85
        • Länssjukhuset i Halmstad
      • Helsingborg, Sweden, 251 87
        • Helsingborgs Lasarett
      • Karlskrona, Sweden, 371 81
        • Blekingesjukhuset Karlskrona
      • Karlstad, Sweden, 651 85
        • Centralsjukhuset i Karlstad
      • Kristianstad, Sweden, 291 85
        • Centralsjukhuset i Kristianstad
      • Linköping, Sweden, 581 85
        • Universitetssjukhuset i Linköping
      • Lund, Sweden, 221 85
        • Skånes Universitetssjukhus, Lund
      • Malmö, Sweden, 205 02
        • Skånes Universitetssjukhus, Malmö
      • Stockholm, Sweden, 171 76
        • Karolinska Universitetssjukhuset i Solna
      • Stockholm, Sweden, 112 81
        • Capio St Görans sjukhus
      • Stockholm, Sweden, 118 83
        • Södersjukhuset/Stockholm South General Hospital
      • Sundsvall, Sweden, 851 86
        • Länssjukhuset Sundsvall-Härnösand
      • Uddevalla, Sweden, 451 80
        • NU-sjukvården, Uddevalla sjukhus
      • Umeå, Sweden, 901 85
        • Norrlands universitetssjukhus
      • Uppsala, Sweden, 751 85
        • Akademiska sjukhuset i Uppsala
      • Västerås, Sweden, 721 89
        • Centrallasarettet i Västerås
      • Växjö, Sweden, 351 85
        • Centrallasaretttet i Växjö
      • Örebro, Sweden, 701 85
        • Universitetssjukhuset I Orebro

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with histologically verified breast cancer planned for neoadjuvant chemotherapy

Description

Inclusion Criteria:

  • clinically node-negative (or unclear nodal status) substudy I
  • signed consent from the study participant

Exclusion Criteria:

  • inflammatory breast cancer
  • cytologically verified lymph node metastasis/es at diagnosis (substudy I), but these patients can be included in substudy II
  • patients not able to give an informed consent
  • hypersensitivity or allergy against blue dye or isotope

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
False negative rate
Time Frame: Up to two years
The rate of patients with no metastasis/ses in their sentinel lymph node/s before neoadjuvant chemotherapy (NAC) but metastasis/ses in the nodes from the axillary lymph node dissection performed after NAC will be analysed. In substudy II we also investigate the false negative rate in sentinel lymph node biopsies performed after NAC if the patient had positive lymph nodes at diagnosis.
Up to two years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification rate
Time Frame: Up to two years
The number of successful sentinel lymph node biopsies among the total number of attempted biopsies. Will be analyses both before and after neoadjuvant chemotherapy.
Up to two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stockholm South General Hospital

Collaborators

Swedish Breast Cancer Group

Investigators

  • Principal Investigator: Linda H Zetterlund, PhD, Dep. of Medical Research and Education, Karolinska Institutet (KI), Stockholm, Sweden
  • Study Chair: Fuat Celebioglu, PhD, Dep. of Medical Research and Education, KI, Stockholm, Sweden
  • Study Chair: Jan Frisell, Professor, Dep. of Molecular Medicine and Surgery, KI, Stockholm, Sweden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2010

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

December 19, 2013

First Submitted That Met QC Criteria

January 7, 2014

First Posted (Estimate)

January 9, 2014

Study Record Updates

Last Update Posted (Actual)

October 28, 2019

Last Update Submitted That Met QC Criteria

October 24, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010/441-31/4

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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