Trial Information

A Phase II Study of Fluorodeoxyglucose (FluGlucoScan) in Patients With Breast Cancer: Correlation With Histologic Findings of Sentinel Node Biopsies and Axillary Dissection

1.0 Introduction

Breast cancer is the most common cancer in North American women. It is estimated that one in
8 American women will develop breast cancer during her lifetime. Surgical treatment has
evolved from radical mastectomy to breast conservation, and systemic treatment has become
increasingly important. The presence or absence of lymph node metastases is the most
important prognostic factor used to determine type of systemic treatment necessary. Axillary
dissection however, carries with it the risk of nerve injury, lymphedema, decreased arm
motion and seroma formation. Clinical examination, ultrasound, CT scanning and MRI of the
axilla are not sensitive or specific enough to eliminate the need for axillary dissection.
Sentinel node biopsy (SNB) can predict the pathologic status of the axilla and theoretically
could differentiate patients into those with positive node biopsies who require full
dissection versus those who are negative and do not. Frozen section of the sentinel node is
inaccurate and therefore SNB positive patients would require two surgical procedures.
Positron Emission Tomography (PET) scanning of the axilla has been reported to have a high
sensitivity and specificity and if used prior to surgery may guide the surgeon in
determining the need for full axillary dissection versus SNB alone. PET scanning has also
been reported to identify unsuspected distant metastases not found on standard staging
examinations. This study will investigate the use of PET scanning in conjunction with SNB
and results of both modalities will be correlated with histologic results of axillary
dissection.

2.0 Objectives

There are no reports describing results of a similar study. By performing a properly
constructed clinical trial in T1 - 3 N0 breast cancer patients, the question of whether PET
scanning will make a difference to patient management can be answered. The hypothesis of
this study is therefore, that a PET scan prior to surgery will facilitate staging both
locally (axilla) and distant and will help the surgeon determine whether to do SNB or
axillary dissection.

2.1 Primary Objective: To determine whether preoperative PET imaging combined with sentinel
node biopsy can accurately identify nodal status. This would be most important in patients
with a negative PET scan and negative sentinel nodes. If the combination of these tests was
found to have a high negative predictive value for nodal metastases, full axillary
dissection could be avoided.

2.2 Secondary Objectives:

- Assess pattern of lymph node drainage using lymphoscintigraphy.

- Assessment of size limitations of PET scanning in metastatic lymph nodes.

- Assessment of primary tumor size and evidence of multifocality as compared to
preoperative imaging (mammography +/- ultrasound).

- The incidence of unsuspected distant metastases and frequency with which treatment was
changed as a result of the PET scan would also be determined.

3.0 Materials and Methods

3.1 Patient Population: Pre and post menopausal women with clinical T1-3 N0 breast cancer
are eligible. All will have biopsy proven breast carcinoma. Positive core or fine needle
aspiration biopsies will be obtained in all patients. Core biopsies are preferred.
Excisional biopsies are not allowed. Patients must not be pregnant or lactating and must not
have had prior malignancy. Diabetic patients are ineligible. An informal survey of 8
patients from Calgary indicates that all 8 would be willing to travel to Edmonton for their
PET scan. (Personal communication from Dr. Mews).

3.2 Preoperative Imaging: All patients will have preoperative mammography +/- ultrasound of
the breast. Patients eligible for and consenting to the study will be referred to the Cross
Cancer Institute by their surgeons and will have preoperative PET scanning. Imaging will be
completed within seven days prior to surgery. Once a PET scanner becomes available in
Calgary, the scans will be done there. Potential sites of distant metastases identified by
PET scan will be imaged further and if necessary, possible biopsies will be obtained to
confirm the diagnosis.

3.3 Surgery: Dr. Kelly Dabbs from Edmonton and Dr. Daphne Mew from Calgary will be the
surgeons involved. They have proven experience in doing SNB's. At the time of surgery,
sentinel node biopsy using both blue dye and colloid will be performed followed by level
I/II axillary dissection. The patients may have either segmental resection or mastectomy.

3.4 Pathology: The sentinel node will be assessed by H&E as well as immunohistochemistry as
per standard protocol. Measurements of primary tumor size, size of axillary metastases and
size of in situ component will be documented. All pathology will be reported by Dr. J.
Danyluk, Dr. R. Berendt and Dr. F. Alexander.

3.5 Outcome Analysis: Patients with positive axillary nodes on dissection and positive SNB
and/or PET will be considered true positive (TP) for that modality. A negative axillary
dissection and negative PET and/or SNB will identify the true negative (TN) group. A
positive axillary dissection and negative PET and/or SNB will identify the false negative
(FN) subgroup. A negative axillary dissection and positive PET and/or SNB will identify the
false positive (FP) subgroup. Sensitivity (TP/TP + FN) and specificity (TN/TN + FP) will be
determined. If patients do not have successful sentinel node surgery or PET scanning, they
will be included in the analysis of the individual modality which was successful.

3.6 Statistics: In order to have an adequate number of node positive patients to test
sensitivity an overall total of 240 patients is required. The proportion of patients who are
node positive is estimated to be 0.35. A sample of 240 is expected to contain 84 node
positive patients and the probability that at least 72 of the 240 patients are node positive
is 0.95. The subsample of 72 node positive patients is sufficient to perform a one-sided
test of equivalence for a target sensitivity of 0.80 and an allowable difference of 0.10
with significance level of 10% and power of 80%.The 168 node negative patients from the 240
total permit a one-sided test of equivalence for which the target specificity is 0.95 and
the allowable difference is 0.05 with significance level of 5% and power of 90%.43