Primary Radioactive Iodine Seed localisation in the Axilla in axillary node positive breast cancer combined with Sentinel node procedure (RISAS) following neoadjuvant chemotherapy (NAC): a novel surgical approach to accurately assess axillary response to neoadjuvant systemic therapy, thereby reducing future need for completion axillary lymph node dissection and subsequent morbidity

Chemotherapy in clinically node positive breast cancer patients is increasingly
administrated in a neoadjuvant setting. The standard treatment regimen in these
cases is then: neoadjuvant chemotherapy (NAC) followed by breast surgery and an
axillary lymph node dissection (ALND). NAC results in axillary pathologic
complete response (pCR) in 1 out of 3 patients, indicating a complete absence
of axillary metastases after completion of NAC. In such events, ALND can be
regarded as overtreatment that creates unnecessary morbidity. Less invasive
axillary surgery which can accurately assess axillary pCR is therefore
preferred over standard ALND in all patients. In case of detection of remaining
axillary lymph node metastases by this less invasive axillary surgical
procedure, completion axillary treatment is standard of care.
The novel RISAS procedure is introduced as a possible less invasive axillary
staging procedure. RISAS procedure contains Radioactive Iodine Seed
localisation in the Axilla in axillary node positive breast cancer combined
with a Sentinel node procedure.

The main goal of this study is to examine the accuracy (identification rate of
the MARI-node and Sentinel node, sensitivity, negative predictive value (NPV)
and false-negative rate (FNR)) of the RISAS procedure compared to the current
standard axillary lymph node dissection in clinically node positive breast
cancer patients, treated with NAC.

The study is designed as an open-single arm multicenter intervention study. In
this study 248 patients will be included during a 2 year period. Patients will
be recruited in:
- Academic Breast Cancer Centre, Erasmus MC, Rotterdam
- Amphia Hospital, Breda
- Maastricht University Medical Centre, Maastricht
- University Medical Centre Utrecht, Utrecht

For this study, it is required that each participating hospital is already
using I-125 seed placement to localize the primary tumor in breast cancer
patients. As a consequence, all participating surgical oncologists are
experienced with the use of I-125 seeds.

a) The RISAS-procedure consists of: insertion of an I-125 seed in a positive
axillary lymph node, prior to the start of NAC. The I-125 seed will be placed
simultaneously with the standard I-125 localisation procedure of the breast
tumor which precludes extra visits. In case of several suspicious nodes on
ultrasound, confirmed by pathology, the I-125 seed will be placed in the most
suspicious node.
b) sentinel lymph node biopsy (SLNB): this procedure is a standard technique in
clinically node negative breast cancer.

During definitive axillary surgery, the ALND is preceded by both selective
excisions of the MARI-node as well as the dual tracer sentinel node(s). It may
occur that both procedures converge in the same axillary lymph node.

Prior to start of NAC, an I-125 seed will be placed in the pathologically
confirmed axillary lymph node metastasis. After completion of NAC, all patients
will undergo a RISAS procedure followed by ALND in a one-step surgical
procedure.

Patients will undergo standard workup and diagnostic procedures and treatments,
according to the Dutch guideline. For this study the RISAS procedure will be
performed, preceding the axillary surgery (i.e. ALND). The RISAS procedure
includes:
a) insertion of an I-125 seed in a positive axillary lymph node, prior to the
start of NAC. The I-125 seed will be placed simultaneously with the standard
I-125 localisation procedure of the breast tumor which precludes extra visits.
The I-125 seed will be placed in the lymph node which has been biopsied, i.e.
node in which a metastasis was confirmed by pathology.
b) sentinel lymph node biopsy (SLNB): this procedure is a standard dual Tc-99
tracer technique in clinically node negative breast cancer.

Patients who will be participating in this study, will not benefit personally
of the RISAS-procedure. However, if RISAS is proven to be an accurate method
for the assessment of axillary pCR, future patients will benefit.