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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02031042
• Other study ID #: 2010/441-31/4
• Status: Completed
• Start date: October 2010
• Est. completion date: December 2015

Study information

• Verified date: October 2019
• Source: Stockholm South General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 224
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Locations

Country	Name	City	State
Sweden	Falu lasarett	Falun
Sweden	Sahlgrenska Universitetssjukhuset, Sahlgrenska	Göteborg
Sweden	Länssjukhuset i Halmstad	Halmstad
Sweden	Helsingborgs lasarett	Helsingborg
Sweden	Blekingesjukhuset Karlskrona	Karlskrona
Sweden	Centralsjukhuset i Karlstad	Karlstad
Sweden	Centralsjukhuset i Kristianstad	Kristianstad
Sweden	Universitetssjukhuset i Linköping	Linköping
Sweden	Skånes Universitetssjukhus, Lund	Lund
Sweden	Skånes Universitetssjukhus, Malmö	Malmö
Sweden	Universitetssjukhuset i Örebro	Örebro
Sweden	Capio St Görans Sjukhus	Stockholm
Sweden	Karolinska Universitetssjukhuset i Solna	Stockholm
Sweden	Södersjukhuset/Stockholm South General Hospital	Stockholm
Sweden	Länssjukhuset Sundsvall-Härnösand	Sundsvall
Sweden	NU-sjukvården, Uddevalla sjukhus	Uddevalla
Sweden	Norrlands Universitetssjukhus	Umeå
Sweden	Akademiska sjukhuset i Uppsala	Uppsala
Sweden	Centrallasarettet i Västerås	Västerås
Sweden	Centrallasaretttet i Växjö	Växjö

Sponsors (2)

Lead Sponsor	Collaborator
Stockholm South General Hospital	Swedish Breast Cancer Group

Country where clinical trial is conducted

Sweden, 

References & Publications (8)

Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N; National Surgical Adjuvant Breast and Bowel Project Protocol B-27. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003 Nov 15;21(22):4165-74. Epub 2003 Oct 14. — View 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. — View 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. — View Citation

Kuerer HM, Sahin AA, Hunt KK, Newman LA, Breslin TM, Ames FC, Ross MI, Buzdar AU, Hortobagyi GN, Singletary SE. Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg. 1999 Jul;230(1):72-8. — View Citation

Mamounas EP, Brown A, Anderson S, Smith R, Julian T, Miller B, Bear HD, Caldwell CB, Walker AP, Mikkelson WM, Stauffer JS, Robidoux A, Theoret H, Soran A, Fisher B, Wickerham DL, Wolmark N. Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2005 Apr 20;23(12):2694-702. Erratum in: J Clin Oncol. 2005 Jul 20;23(21):4808. Sovan, Atilla [corrected to Soran, Atilla]. — View 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. — View 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. — View Citation

Xing Y, Foy M, Cox DD, Kuerer HM, Hunt KK, Cormier JN. Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer. Br J Surg. 2006 May;93(5):539-46. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	False negative rate	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	Identification rate	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

External Links

•   Homepage for the Swedish Breast Surgical Association