Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04865549 |
| Other study ID # |
HCB/2016/0296 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2016 |
| Est. completion date |
January 1, 2021 |
Study information
| Verified date |
April 2021 |
| Source |
Hospital Clinic of Barcelona |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The status of the axillary lymph nodes is one of the main prognostic factors in breast cancer
(BC). SLNB is currently the standard staging method for patients with clinically
node-negative (cN0) breast cancer. In patients with a positive SLN and in those with affected
lymph nodes at the beginning (cN+), LND is the standard of treatment.
Description:
Breast cancer (BC) is the most common malignant tumor and the one that causes the highest
number of deaths among women around the world. In Spain some 25,000 new cases are diagnosed
per year, which represents almost 30% of all female tumors. In Catalonia, the incidence is
83.9 cases / 100,000 inhabitants, while the national average is 50.9 cases / 100,000
inhabitants.
Thanks to screening programs and the awareness of patients and professionals, the majority of
diagnosed cases are found in an early stage of the disease. In early stages, the prognosis is
excellent with a 5-year survival greater than 80%.
Lymph node staging: selective sentinel node biopsy (SLNB) vs axillary lymphadenectomy The
status of the axillary lymph nodes is one of the main prognostic factors. Knowing the lymph
node status allows the disease to be staged and modulates locoregional and systemic
treatment. Lymph node staging and management of axillary disease have changed dramatically in
recent decades.
SLNB is currently the standard staging method for patients with clinically node-negative
(cN0) breast cancer. When SLN is negative, axillary lymph node dissection (LND) can be
omitted without prejudice to patient survival or locoregional control of the disease. In
patients with a positive SLN and in those with affected lymph nodes at the beginning (cN+),
LND is the standard of treatment. Morbidity associated with this technique affects up to 80%
of patients and includes: chronic lymphedema of the upper limb (20-30%), seromas (50-60%)
that in many cases require repeated punctures for drainage, infection of the wound (5-15%)
that requires antibiotic treatment and sometimes drainage, decreased mobility of the arm or
"frozen shoulder" (up to 10%) that requires rehabilitation treatment, neuropathic pain due to
injury to the intercostobrachial nerve (5- 20%) and other less frequent ones such as hematoma
or section of the long thoracic nerves (which produces a scapula alata) or the latissimus
dorsi. It is obvious that all these complications affect the quality of life of patients and
their emotional state. LND lengthens the days of hospitalization and this, together with the
treatment of associated complications, substantially increases healthcare costs.
Current focus on the initial treatment of breast cancer: primary systemic treatment Advances
in biological knowledge of the disease and in systemic treatments have led to an increasing
number of patients with BC starting with systemic therapy, relegating surgery to a second
stage. This approach evaluates the tumor response in vivo to systemic treatment and provides
critical prognostic information. In addition, the decrease and even disappearance of the
tumor increases the chances of offering a conservative surgery in the breast. Response rates
vary according to the biological type of tumor and the treatment used, being higher for Her2+
tumors treated with chemotherapy combined with anti-Her2 antibodies.
In cN0 patients receiving neoadjuvant chemotherapy (NCT), SLNB can be performed before or
after. Performing it later, together with breast surgery, has the advantage of saving the
patient a surgical procedure. This strategy is supported by numerous studies that show
detection and false negative (FN) rates comparable to those of patients who undergo SLNB
before neoadjuvant treatment.
In those patients who present clinically positive lymph nodes (cN +) before initiating
neoadjuvancy, the standard strategy in relation to the axilla is to perform LND. However, in
40-50% of patients, lymph node disease disappears with treatment. Nodal response is greater
in tumors with estrogen receptor negative, high histologic grade, and Her2 overexpression. It
follows that up to 40-50% of unnecessary lymphadenectomies are currently being carried out.
Application of the SLNB in cN + patients undergoing neoadjuvant chemotherapy Due to the
benefits that SLNB represents in cN0 patients and the complete response rates in the axilla
after neoadjuvant chemotherapy (NAC) in initial cN+ patients, the question arises as to
whether SLNB can be valid in these patients. Previous studies in which SLNB was performed in
clinically node-positive patients who received NAC have shown FN rates of up to 25%. The
Spanish Society of Senology and Breast Pathology (SESPM) recommends for the validation of the
SLN technique to obtain a detection rate equal to or greater than 95% and a FN rate equal to
or less than 5%. International literature accepts FN rates equal to or less than 10%.
The success of SLNB after NAC may be affected by altered lymphatic drainage of the breast
during chemotherapy. On the other hand, it is possible that the regression of the axillary
disease does not follow an orderly and uniform pattern, reducing the reliability of the
technique. Finally, the impact that a FN of the technique may have on the prognosis of these
patients is unknown, and it is probably not the same as in a cN0 patient.
The American College of Surgeons Oncology Group (ACOSOG) conducted a phase II trial that
included patients with BC T1-4, N1-2, M0. The patients received primary chemotherapy and
subsequently SLNB plus LND. The detection rate was 92.9%. There was a complete pathological
response in the axilla in 41% of the patients. The FN rate was 12.6% (higher than the
accepted 10%). The conclusion was that SLN biopsy cannot be recommended for these patients at
this time.
The multicenter study SENTINA (SENTinel NeoAdjuvant), carried out in Germany and Austria,
evaluated in one of its arms the performance of SLNB in cN + patients who converted to cN0
with NAC. The SLN detection rate and the FN rate were 80.1% and 14.2%, respectively. None of
these studies evaluate the results of the technique based on the biological profile of the
tumor or the response of the disease to treatment.
It is imperative to correctly select patients and apply new strategies to optimize the
results of SLNB in order to identify regression of axillary disease and to avoid radicality
of LA.
New strategies: placement of a marker in the metastatic lymph node. Assessment of the
response according to the biological profile of the tumor and its impact on the rate of FN
Axillary ultrasound prior to neoadjuvancy is performed to detect possible lymph node
involvement and, together with biopsy of the suspicious node, offers a sensitivity and
specificity of 25% -95% and 97% -100%, respectively. Its application could be useful to
assess axillary lymph node response. Patients with normal-appearing axillary nodes on
ultrasound are likely to be less likely to have residual disease.
The placement of a marker in the biopsied pathological node that allows its identification
during the surgical act and to check whether or not it correlates with the SLN can be useful
strategies to reduce the rate of FN of the SLNB.
The response of the disease in the breast and in the lymph nodes to NAC is different
depending on the biological profile of the tumor. The axillary response to treatment may have
an impact on the rate of FN of SLNB. Studying the results of the technique according to the
biological profile of the tumor can help us to better select the candidate patients for the
application of the technique.
