Clinical trial NCT02240472: Sentinel Node Biopsy in Breast Cancer: Omission of Axillary Clearance After Macrometastases. A Randomized Trial.
Official title: Survival and Axillary Recurrence Following Sentinel Node-positive Breast Cancer Without Completion Axillary Lymph Node Dissection - a Randomized Study of Patients With Macrometastases in the Sentinel Node
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: sentinel node biopsy, lymph node metastasis, survival
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: The Swedish Research Council
name: Swedish Cancer Foundation
name: Nordic Cancer Union
First posted: 2014-09-15
Enrollment: 2700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Since the introduction of sentinel node biopsy in breast cancer, it has become clear that its use is reliable and reproducible. Today, it is clinical routine to not remove further lymph nodes from the axilla (arm pit) in case the sentinel node (which is the first lymph node/s reached by lymphatic flow from the breast) is free of tumor deposits. It is also routine to leave remaining lymph nodes behind in case the sentinel node contains a minimal cluster of tumor cells, called isolated tumor cells (formerly submicrometastasis). Even in slightly larger tumor deposits, so called micrometastasis (up to 2 mm in size), it has been shown that a completion axillary clearance (removal of further lymph nodes from the arm pit) does not contribute to a better survival. Data from a randomized study indicate that it seems safe to omit axillary clearance even if the sentinel node biopsy shows up to 2 nodes with tumor deposits over 2 mm in size (macrometastasis). These studies have changed clinical practice in many countries, however, it is still debated whether it is safe to omit axillary clearance in the case of sentinel node macrometastasis due to under-recruitment in the aforementioned study. The rationale for omitting extensive axillary surgery is the avoidance of postoperative morbidity such as arm lymphedema, loss of sensation, pain and swelling.

The hypothesis is that refraining from axillary clearance in breast cancer patients with 1-2 sentinel nodes with macrometastasis will not worsen breast cancer-specific survival by more than a maximum of 2.5% after 5 years.

This study is a prospective international randomized trial including 3500 patients.

Breast cancer patients without signs of axillary nodal involvement will be eligible for sentinel node biopsy. Those who are found to have up to two sentinel node containing macrometastasis will be informed about this trial Those wishing to participate will be randomized to either undergo further axillary surgery (clearance) or not. Outcome measures are breast cancer-specific survival, disease-free survival, axillary recurrence rate and overall survival.

Detailed description: Details can be found on www.senomac.se

Eligibility criteria: Inclusion Criteria:

* Patients with invasive breast cancer (T1-T3)
* N0 on palpation
* Preoperative ultrasound performed
* Pathology report shows macrometastasis in 1-2 sentinel lymph nodes
* Patients undergo breast-conserving therapy or mastectomy
* The patient must have provided oral and written consent
* Age ≥ 18 years

Exclusion Criteria:

* Metastases outside of the ipsilateral axilla
* Prior history of invasive breast cancer
* Pregnancy
* Bilateral breast cancer if one side meets exclusion criteria
* Medical contraindication for radiotherapy or systemic treatment
* Inability to absorb or understand the meaning of the study information; for example, through disability, inadequate language skills or dementia.

Primary outcomes:
measure: breast cancer-specific survival
timeFrame: up to 15 years
Secondary outcomes:
measure: disease-free survival
timeFrame: 5, 10 and 15 years
measure: axillary recurrence rate
timeFrame: 5, 10 and 15 years
measure: overall survival
timeFrame: 5, 10 and 15 years
Other outcomes:
Locations:
city: Aabenraa
country: Denmark
facility: Sygehus Sonderjylland
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Esbjerg
country: Denmark
facility: Sydvestjysk Sygehus
city: Lillebaelt
country: Denmark
facility: Sygehus Lillebaelt
city: Odense
country: Denmark
facility: Odense University Hospital
city: Randers
country: Denmark
facility: Randers Regionshospitalet
city: Viborg
country: Denmark
facility: Regionshospitalet Viborg
city: Athens
country: Greece
facility: Athens University Hospital
city: Gävle
country: Sweden
facility: Gävle sjukhus
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Halmstad
country: Sweden
facility: Hallands sjukhus
city: Helsingborg
country: Sweden
facility: Helsingborg lasarett
city: Jönköping
country: Sweden
facility: Länssjukhuset Ryhov
city: Kalmar
country: Sweden
facility: Kalmar sjukhus
city: Karlskrona
country: Sweden
facility: Blekinge sjukhuset
city: Karlstad
country: Sweden
facility: Karlstad sjukhus
city: Kristianstad
country: Sweden
facility: Central Hospital Kristianstad
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Lund
country: Sweden
facility: Malmö/Lund University Hospital
city: Skövde/Lidköping
country: Sweden
facility: Skaraborgs sjukhus
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Southern Gerenal Hospital
city: Stockholm
country: Sweden
facility: St. Görans Hospital
city: Sundsvall
country: Sweden
facility: Sundsvall länssjukhus
city: Uddevalla
country: Sweden
facility: Uddevalla sjukhus
city: Umeå
country: Sweden
facility: Umeå University Hospital
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Varberg
country: Sweden
facility: Varbergs sjukhus
city: Västervik
country: Sweden
facility: Västervik Hospital
city: Västerås
country: Sweden
facility: Västerås Central Hospital
city: Örebro
country: Sweden
facility: Örebro University Hospital
Study officials:
affiliation: Karolinska Institutet
name: Jana de Boniface, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska University Hospital
name: Jan Frisell, Professor
role: STUDY_CHAIR
affiliation: Central Hospital Västerås
name: Leif Bergkvist, Professor
role: STUDY_CHAIR
affiliation: Central Hospital Västerås
name: Yvette Andersson, PhD
role: STUDY_CHAIR
affiliation: Lund University
name: Lisa Ryden, Professor
role: STUDY_CHAIR
affiliation: Umeå University Hospital
name: Malin Sund, Professor
role: STUDY_CHAIR
affiliation: Sahlgrenska University Hospital
name: Olofsson Roger, PhD
role: STUDY_CHAIR
affiliation: Region Örebro County
name: Johan Ahlgren, PhD
role: STUDY_CHAIR
affiliation: Sahlgrenska University Hospital
name: Dan Lundstedt, PhD
role: STUDY_CHAIR
affiliation: Aarhus University Hospital, Denmark
name: Peer Christiansen, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet Copenhagen, Dnmark
name: Tove Tvedskov Filtenborg, MD
role: STUDY_CHAIR
affiliation: University of Athens
name: Michalis Kontos, PhD
role: STUDY_CHAIR
affiliation: University of Aarhus
name: Birgitte Offersen, Professor
role: STUDY_CHAIR
affiliation: Klinikum Esslingen
name: Thorsten Kühn, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Universität Rostock
name: Toralf Reimer, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: San Raffaele Hospital, Milano
name: Oreste Gentilini
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Salzburg
name: Roland Reitsamer
role: PRINCIPAL_INVESTIGATOR
References:
citation: Appelgren M, Sackey H, Wengstrom Y, Johansson K, Ahlgren J, Andersson Y, Bergkvist L, Frisell J, Lundstedt D, Ryden L, Sund M, Alkner S, Vrou Offersen B, Filtenborg Tvedskov T, Christiansen P, de Boniface J; SENOMAC Trialists' Group. Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial. Breast. 2022 Jun;63:16-23. doi: 10.1016/j.breast.2022.02.013. Epub 2022 Mar 1.
citation: de Boniface J, Ahlgren J, Andersson Y, Bergkvist L, Frisell J, Lundstedt D, Olofsson Bagge R, Ryden L, Sund M; SENOMAC Trialists' Group. The generalisability of randomised clinical trials: an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer. Breast Cancer Res Treat. 2020 Feb;180(1):167-176. doi: 10.1007/s10549-020-05537-1. Epub 2020 Jan 27.
citation: de Boniface J, Frisell J, Andersson Y, Bergkvist L, Ahlgren J, Ryden L, Olofsson Bagge R, Sund M, Johansson H, Lundstedt D; SENOMAC Trialists' Group. Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial. BMC Cancer. 2017 May 26;17(1):379. doi: 10.1186/s12885-017-3361-y.