TAD in Primary Breast Cancer With Initially ≥ 3 Suspicious Lymph Nodes

Breast Cancer Clinical Trial

— SenTa2  

Official title:

Prospective, Multicentric Registry Study Evaluating the False-negative Rate of Targeted Axillary Dissection (TAD) in Primary Breast Cancer With Initially ≥ 3 Suspicious Lymph Nodes Under Neoadjuvant Systemic Therapy (SenTa 2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05462457
• Other study ID #: Version 1.0_16.08.2021
• Status: Recruiting
• Start date: March 7, 2022
• Est. completion date: March 2032

Study information

• Verified date: February 2023
• Source: Kliniken Essen-Mitte
• Contact: Oliver Halfmann
• Phone: +49201174
• Email: O.Halfmann[@]kem-med.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Due to high pathological complete remission (pCR) rates in both breast and lymph nodes (ypT0/Tis, ypN0) following neoadjuvant systemic therapy (NST) in many patients with initially clinically node-positive (cN+) breast cancer, the standard treatment of the axilla has changed from axillary lymph node dissection (ALND), which is associated with high morbidity, to less invasive, surgical approaches. In several studies, targeted axillary dissection (TAD) has presented with false-negative rates (FNRs) less than 5%, however, in patients with high initial lymph node involvement (≥ 3 clinically suspicious lymph nodes) TAD has not been thoroughly investigated. The present prospective registry study aims to evaluate the FNR of TAD in patients with ≥ 3 initially suspicious lymph nodes and clinically node-negative status (ycN0) after NST in comparison to ALND.

Description:

Patients with triple-negative breast cancer (TNBC) or human epidermal growth factor receptor 2 (HER2) positive breast cancer achieved pCR rates of 50-70% following NST. In the multicenter prospective SenTa study (NCT03102307), the axillary pCR rate after the end of NST in 473 initially cN+ patients was 60.3%. Therefore, less invasive surgical techniques have been investigated to avoid the morbidity associated with ALND. One of these minimally invasive methods called TAD involves the combined intraoperative excision of the pre-NST marked most suspicious lymph node (target lymph node, TLN) and sentinel lymph nodes (SLNs). In a pooled analysis of 13 studies including 521 patients who had undergone TAD, the FNR of TAD was 5.2%. The FNR of TAD in breast cancer patients with high initial lymph node (LN) involvement (≥ 3 clinically suspicious LNs) has so far hardly been investigated. In a very small cohort, a FNR of 0% was obtained for patients with 1-3 suspicious LNs (cN1, n = 10), 33% for patients with 4-9 suspicious LNs (cN2, n = 3) and 100% for patients with 10 or more suspicious LNs (cN3, n = 2). In addition, patients with high lymph node involvement are often excluded from some larger studies evaluating TAD or other axillary surgical approaches. In consequence, the FNR of TAD LNs in comparison to LNs obtained during ALND in the patient group with ≥ 3 clinically positive LNs needs to be evaluated in a larger cohort, since extensive initial LN involvement is associated with a higher probability that a false-negative result of TAD could cause one or more involved LNs to be left in the axilla, if only TAD and not ALND is performed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: March 2032
• Est. primary completion date: March 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• signed informed consent form
• female/male patient aged = 18 years
• clinical (c) tumor stage T1-4c, bilateral breast cancer and multifocal tumor allowed
• invasive breast cancer confirmed by core biopsy
• clinically node positive (cN+) (by means of axillary ultrasound or other imaging methods) with = 3 clinically suspicious lymph nodes
• biopsy-proven axillary lymph node involvement
• marking (e.g. with a clip, magnetic seed, carbon suspension) of the clinically suspicious lymph node(s) before the start of NST
• without distant metastases
• indication for NST including chemotherapy
• TAD + ALND planned
• at least 7 lymph nodes (TAD + ALND) planned for histological analysis

Exclusion Criteria:

• cN0 or cN+ with = 2 clinically suspicious lymph nodes
• patients without indication for NST or NST < 12 weeks
• NST without chemotherapy
• adjuvant/ neoadjuvant therapy already started prior to inclusion in the study
• patients for whom only ALND is planned
• ycN+ (by means of axillary ultrasound or other imaging methods)
• recurrent breast cancer
• larger surgery of the breast (starting from quadrant resection) or the axilla prior to the study
• previous radiotherapy of the breast or axilla
• inflammatory breast cancer
• extramammary breast cancer
• pregnant women
• not able to undergo surgery
• inability to understand the purpose of the clinical study or to comply with study conditions

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Node-positive Breast Cancer

Intervention

Procedure:
• Targeted axilllary dissection (TAD) followed by axillary lymph node dissection (ALND)
Intraoperative excision of TAD lymph nodes followed by ALND in the same surgical session or secondary surgical intervention

Locations

Country	Name	City	State
Germany	Kliniken Essen-Mitte (KEM)	Essen

Sponsors (1)

Lead Sponsor	Collaborator
Kliniken Essen-Mitte

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Kuemmel S, Heil J, Rueland A, Seiberling C, Harrach H, Schindowski D, Lubitz J, Hellerhoff K, Ankel C, Grasshoff ST, Deuschle P, Hanf V, Belke K, Dall P, Dorn J, Kaltenecker G, Kuehn T, Beckmann U, Potenberg J, Blohmer JU, Kostara A, Breit E, Holtschmidt J, Traut E, Reinisch M. A Prospective, Multicenter Registry Study to Evaluate the Clinical Feasibility of Targeted Axillary Dissection (TAD) in Node-positive Breast Cancer Patients. Ann Surg. 2022 Nov 1;276(5):e553-e562. doi: 10.1097/SLA.0000000000004572. Epub 2020 Nov 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	False-negative rate (FNR) of TAD in patients with ycN0 status	The FNR of TAD is calculated as the number of patients with histologically negative TAD lymph nodes (LNs) who were found to have positive LNs in the ALND specimen, divided by the total number of patients with positive LNs.	Postoperatively immediately after histopathological evaluation of LNs
Secondary	Detection rate of preoperative ultrasound	Preoperative detection rate (DR) of initially marked target lymph nodes (TLNs) on ultrasound images after the end of NST	Preoperatively
Secondary	Localization of TLNs	Successful localization with e.g. wire, magnetic marker, or reflector clip of the marked TLNs	Preoperatively or during NST
Secondary	Detection rate of TAD	Successful intraoperative identification of at least one SLN and one TLN, including cases with TLN = SLN	At the time of surgery
Secondary	Detection rate of target lymph node biopsy (TLNB)	Successful intraoperative identification of TLN(s)	At the time of surgery
Secondary	Detection rate of sentinel lymph node biopsy (SLNB)	Successful intraoperative identification of SLN(s)	At the time of surgery
Secondary	FNR of TLNB	The FNR of TLNB is calculated as the number of patients with histologically negative TLNs who were found to have positive SLNs and/or positive LNs in the ALND specimen, divided by the total number of patients with positive LNs.	Postoperatively immediately after histopathological evaluation of LNs
Secondary	FNR of SLNB	The FNR of SLNB is calculated as the number of patients with negative SLNs who were found to have positive TLNs and/or positive LNs in the ALND specimen, divided by the total number of patients with positive LNs.	Postoperatively immediately after histopathological evaluation of LNs
Secondary	FNR of preoperative ultrasound	False-negative is defined as preoperative ycN0 status on axillary ultrasound images and pathological ypN+ after surgery	Postoperatively immediately after histopathological evaluation of LNs
Secondary	Rate of local recurrence	Proportion of patients with ipsilateral or contralateral recurrence in the breast and/or axilla occurring at any time after surgery.	5 years after surgery, interim analysis: 2 years after surgery
Secondary	Rate of distant recurrence	Proportion of patients with distant recurrence occurring at any time after surgery.	5 years after surgery, interim analysis: 2 years after surgery
Secondary	Invasive disease-free-survival (iDFS)	iDFS is calculated as the time from surgery to the occurrence of either local recurrence, distant recurrence, second malignant disease (breast or different origin), or death from any cause.	5 years after surgery, interim analysis: 2 years after surgery
Secondary	Overall survival (OS)	OS is calculated as the time from surgery to death from any cause	5 years after surgery, interim analysis: 2 years after surgery