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

Recruiting
Conditions
Node-positive Breast Cancer
Breast Cancer
Registration Number
NCT05462457
Lead Sponsor
Kliniken Essen-Mitte
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
150
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
False-negative rate (FNR) of TAD in patients with ycN0 statusPostoperatively immediately after histopathological evaluation of LNs

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.

Secondary Outcome Measures
NameTimeMethod
Detection rate of sentinel lymph node biopsy (SLNB)At the time of surgery

Successful intraoperative identification of SLN(s)

Detection rate of preoperative ultrasoundPreoperatively

Preoperative detection rate (DR) of initially marked target lymph nodes (TLNs) on ultrasound images after the end of NST

Localization of TLNsPreoperatively or during NST

Successful localization with e.g. wire, magnetic marker, or reflector clip of the marked TLNs

Detection rate of TADAt the time of surgery

Successful intraoperative identification of at least one SLN and one TLN, including cases with TLN = SLN

Detection rate of target lymph node biopsy (TLNB)At the time of surgery

Successful intraoperative identification of TLN(s)

FNR of TLNBPostoperatively immediately after histopathological evaluation of LNs

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.

FNR of preoperative ultrasoundPostoperatively immediately after histopathological evaluation of LNs

False-negative is defined as preoperative ycN0 status on axillary ultrasound images and pathological ypN+ after surgery

Rate of local recurrence5 years after surgery, interim analysis: 2 years after surgery

Proportion of patients with ipsilateral or contralateral recurrence in the breast and/or axilla occurring at any time after surgery.

FNR of SLNBPostoperatively immediately after histopathological evaluation of LNs

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.

Rate of distant recurrence5 years after surgery, interim analysis: 2 years after surgery

Proportion of patients with distant recurrence occurring at any time after surgery.

Overall survival (OS)5 years after surgery, interim analysis: 2 years after surgery

OS is calculated as the time from surgery to death from any cause

Invasive disease-free-survival (iDFS)5 years after surgery, interim analysis: 2 years after surgery

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.

Trial Locations

Locations (1)

Kliniken Essen-Mitte (KEM)

🇩🇪

Essen, Germany

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