Clinical trial NCT02031042: Sentinel Node Biopsy Before and/or After Neoadjuvant Chemotherapy in Breast Cancer
Official title: Sentinel Node Biopsy Before and/or After Neoadjuvant Chemotherapy in Breast Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Keywords: neoadjuvant chemotherapy
breast cancer
sentinel lymph node biopsy
false negative rate
identification rate
Lead sponsor: Stockholm South General Hospital
Sponsor class: OTHER
Collaborators: name: Swedish Breast Cancer Group
First posted: 2014-01-09
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with histologically verified breast cancer planned for neoadjuvant chemotherapy

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: False negative rate
timeFrame: Up to two years
Secondary outcomes:
measure: Identification rate
timeFrame: Up to two years
Other outcomes:
Locations:
city: Falun
country: Sweden
facility: Falu lasarett
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset, Sahlgrenska
city: Halmstad
country: Sweden
facility: Länssjukhuset i Halmstad
city: Helsingborg
country: Sweden
facility: Helsingborgs lasarett
city: Karlskrona
country: Sweden
facility: Blekingesjukhuset Karlskrona
city: Karlstad
country: Sweden
facility: Centralsjukhuset i Karlstad
city: Kristianstad
country: Sweden
facility: Centralsjukhuset i Kristianstad
city: Linköping
country: Sweden
facility: Universitetssjukhuset i Linköping
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus, Lund
city: Malmö
country: Sweden
facility: Skånes Universitetssjukhus, Malmö
city: Stockholm
country: Sweden
facility: Capio St Görans Sjukhus
city: Stockholm
country: Sweden
facility: Södersjukhuset/Stockholm South General Hospital
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset i Solna
city: Sundsvall
country: Sweden
facility: Länssjukhuset Sundsvall-Härnösand
city: Uddevalla
country: Sweden
facility: NU-sjukvården, Uddevalla sjukhus
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset i Uppsala
city: Västerås
country: Sweden
facility: Centrallasarettet i Västerås
city: Växjö
country: Sweden
facility: Centrallasaretttet i Växjö
city: Örebro
country: Sweden
facility: Universitetssjukhuset i Örebro
Study officials:
affiliation: Dep. of Medical Research and Education, Karolinska Institutet (KI), Stockholm, Sweden
name: Linda H Zetterlund, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Medical Research and Education, KI, Stockholm, Sweden
name: Fuat Celebioglu, PhD
role: STUDY_CHAIR
affiliation: Dep. of Molecular Medicine and Surgery, KI, Stockholm, Sweden
name: Jan Frisell, Professor
role: STUDY_CHAIR
References:
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citation: Schrenk P, Hochreiner G, Fridrik M, Wayand W. Sentinel node biopsy performed before preoperative chemotherapy for axillary lymph node staging in breast cancer. Breast J. 2003 Jul-Aug;9(4):282-7. doi: 10.1046/j.1524-4741.2003.09406.x.
citation: Papa MZ, Zippel D, Kaufman B, Shimon-Paluch S, Yosepovich A, Oberman B, Sadetzki S. Timing of sentinel lymph node biopsy in patients receiving neoadjuvant chemotherapy for breast cancer. J Surg Oncol. 2008 Nov 1;98(6):403-6. doi: 10.1002/jso.21128.
citation: Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, Lebeau A, Liedtke C, von Minckwitz G, Nekljudova V, Schmatloch S, Schrenk P, Staebler A, Untch M. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013 Jun;14(7):609-18. doi: 10.1016/S1470-2045(13)70166-9. Epub 2013 May 15.
citation: Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, Leitch AM, Kuerer HM, Bowling M, Flippo-Morton TS, Byrd DR, Ollila DW, Julian TB, McLaughlin SA, McCall L, Symmans WF, Le-Petross HT, Haffty BG, Buchholz TA, Nelson H, Hunt KK; Alliance for Clinical Trials in Oncology. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013 Oct 9;310(14):1455-61. doi: 10.1001/jama.2013.278932.
citation: Zetterlund L, Celebioglu F, Axelsson R, de Boniface J, Frisell J. Swedish prospective multicenter trial on the accuracy and clinical relevance of sentinel lymph node biopsy before neoadjuvant systemic therapy in breast cancer. Breast Cancer Res Treat. 2017 May;163(1):93-101. doi: 10.1007/s10549-017-4163-2. Epub 2017 Feb 17.