Trial Information

Cohort Study of Axillary Recurrences and Survival After Negative Negative Sentinel Node Biopsy Without Completion Axillary Clearance

Axillary lymph node dissection (ALND) was previously the standard axillary staging procedure
in breast cancer patients. However, ALND is accompanied by a considerable morbidity,
including seroma formation, lymphedema, neuropathy of the arm with numbness, stiffness,
impaired shoulder movement and pain. Sentinel lymph node biopsy (SLNB) has evolved as a mean
to decrease this morbidity, and validation studies have demonstrated the accuracy of the
method.

With the intent of studying axillary recurrence after negative SLNB for patients in which
completion ALND were omitted, consecutive breast cancer patients were included in the
Swedish Sentinel Node Multicenter Cohort Study between September 2000 and January 2004.

Patients with a unifocal, invasive breast cancer less than 3 cm in diameter were eligible
for enrollment. Exclusion criteria were palpable regional lymph nodes, neoadjuvant chemo- or
radiotherapy, pregnancy, known allergic reactions to blue dye or isotope, previous surgery
in the ipsilateral breast, and preoperatively diagnosed tumor multifocality.

Surgical procedure:

After the preoperative injection of 40-60 mBq Technetium-99 nanocolloid (Solco Nanocoll®)
and 1 ml blue dye (Patent Blue V®), sentinel lymph node (SLN) biopsy was performed. If no
sentinel node could be identified, ALND of levels I and II was performed. A completion ALND
was also performed in the event of a positive SLN biopsy, if lymph nodes clearly suspicious
of metastasis were detected during surgery, or if the primary tumor in the breast was found
to be multifocal on pathological examination.

Pathological assessment:

Frozen sections were obtained from each SLN and examined peroperatively. If a sentinel lymph
node was smaller than 4 mm, two sections were analyzed separately. Nodes larger than 4 mm
were bisected, and two sections from each half analyzed. According to the study protocol, at
least three sections were prepared from the sentinel node or each part of a bisected node
for definitive histopathology. Sections were stained with haematoxylin and eosin (HE). If no
cancer cells were detected, immunohistochemistry (IHC) with cytokeratin antibodies was also
performed.

Non-sentinel lymph nodes were examined by routine staining (HE) according to the protocol of
each pathology department.

Treatment and follow-up:

Adjuvant treatment combinations were given according to national and regional treatment
guidelines, based on tumor characteristics, lymph node status, and surgical treatment.
Patients with isolated tumor cells were regarded as lymph node-negative. If
breast-conserving surgery had been performed, radiation therapy to the breast was given,
which was extended to include the regional lymph nodes in case of axillary lymph node
metastases.

Chemotherapy was offered to all patients with lymph node metastases or those with a
combination of unfavorable primary tumor characteristics (large tumor, high Elston score,
progesterone receptor negativity), after consideration of their general health. Endocrine
therapy was offered to all patients with estrogen or progesterone receptor-positive tumors
larger than 10 mm. The actual reported adjuvant treatment is controlled for in the analyses.

Patients were followed prospectively. The research protocol postulated an annual follow-up
with mammography and clinical examination.

After enrollment, data sheets, including information on primary tumor characteristics,
number of sentinel and non-sentinel lymph nodes with and without metastasis, and given
adjuvant treatment, were computerized. The study was approved by the ethics committee of
Karolinska Institutet, Stockholm, and each region's local ethics committee. All patients
gave written informed consent.