Clinical trial NCT05462457: TAD in Primary Breast Cancer With Initially ≥ 3 Suspicious Lymph Nodes
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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Cancer
Node-positive Breast Cancer
Keywords: Targeted axillary dissection
TAD
False-negative rate
Lead sponsor: Kliniken Essen-Mitte
Sponsor class: OTHER
First posted: 2022-07-18
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with primary breast cancer and ≥ 3 (initially) clinically positive lymph nodes with an indication for NST and in whom TAD + ALND is planned when ycN0 status is achieved after the end of NST.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: False-negative rate (FNR) of TAD in patients with ycN0 status
timeFrame: Postoperatively immediately after histopathological evaluation of LNs
Secondary outcomes:
measure: Detection rate of preoperative ultrasound
timeFrame: Preoperatively
measure: Localization of TLNs
timeFrame: Preoperatively or during NST
measure: Detection rate of TAD
timeFrame: At the time of surgery
measure: Detection rate of target lymph node biopsy (TLNB)
timeFrame: At the time of surgery
measure: Detection rate of sentinel lymph node biopsy (SLNB)
timeFrame: At the time of surgery
measure: FNR of TLNB
timeFrame: Postoperatively immediately after histopathological evaluation of LNs
measure: FNR of SLNB
timeFrame: Postoperatively immediately after histopathological evaluation of LNs
measure: FNR of preoperative ultrasound
timeFrame: Postoperatively immediately after histopathological evaluation of LNs
measure: Rate of local recurrence
timeFrame: 5 years after surgery, interim analysis: 2 years after surgery
measure: Rate of distant recurrence
timeFrame: 5 years after surgery, interim analysis: 2 years after surgery
measure: Invasive disease-free-survival (iDFS)
timeFrame: 5 years after surgery, interim analysis: 2 years after surgery
measure: Overall survival (OS)
timeFrame: 5 years after surgery, interim analysis: 2 years after surgery
Other outcomes:
Locations:
city: Essen
country: Germany
facility: Kliniken Essen-Mitte (KEM)
Study officials:
affiliation: Breast Unit, Kliniken Essen-Mitte, Essen, Germany
name: Sherko Kuemmel, Prof. Dr.
role: STUDY_CHAIR
affiliation: Breast Unit, Kliniken Essen-Mitte, Essen, Germany
name: Mattea Reinisch, Dr.
role: STUDY_CHAIR
References:
citation: 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.