F-18 16 Alpha-Fluoroestradiol-Labeled Positron Emission Tomography in Predicting Response to First-Line Hormone Therapy in Patients With Stage IV Breast Cancer

PRIMARY OBJECTIVES:

I. Estimate the ability of [^18F] FES positron emission tomography (PET) or PET/computed
tomography (CT) uptake at the level of standard uptake value (SUV) < 1.5 to predict overall
response (OR) to first line endocrine therapy for metastatic breast cancer.

SECONDARY OBJECTIVES:

I. Evaluate the independent role of [^18F] FES in predicting response and time to progression
in patients treated with first-line endocrine therapy for metastatic breast cancer.

II. Examine the role of [^18F] FES in predicting OR or clinical benefit (CB), in concert with
tissue assay of levels of estrogen receptor (ER) messenger ribonucleic acid (mRNA) measured
using quantitative polymerase chain reaction (PCR), and semi-quantitative interpretation of
estrogen receptor (ER), progesterone receptor (PgR), androgen receptor (AR), and human
epidermal growth factor-2 (HER2), in addition to serial measures of hormone levels in plasma.

III. Evaluate the relationships among [^18F] FES, semi-quantitative ER from
immunohistochemistry (IHC), and ER mRNA as measured by quantitative PCR.

IV. Document the safety profile of [^18F] FES PET in newly diagnosed patients with metastatic
breast cancer.

V. Evaluate FES SUV < 1.5 as the optimal cutpoint for predicting OR to first-line endocrine
therapy for metastatic breast cancer.

VI. Estimate the rate of [^18F] FES SUV < 1.5 in newly diagnosed metastatic breast cancer
patients planning a course of endocrine therapy.

OUTLINE:

Patients undergo [^18F] FES PET scan. Patients also undergo standard clinical fludeoxyglucose
F 18 (FDG)-PET or FDG-PET/CT scan up to 14 days prior to [^18F] FES PET scan.

After completion of study treatment, patients are followed up for at least 6 months.

Inclusion Criteria:

- Patients will have pathologically confirmed invasive breast cancer with clinical,
radiographic and/or pathologic evidence of stage IV disease; patients must have tissue
blocks available from biopsy of at least one site of metastatic disease and/or from
diagnosis of their primary breast cancer

- Disease may be measurable (by Response Evaluation Criteria in Solid Tumors [RECIST]
criteria) or non-measurable but must be present in at least one non-liver site and
imageable on FDG PET scan; in patients with non-measurable disease by RECIST criteria,
one of the following may be used to assess and follow disease: MUC-1 antigen level
(either cancer antigen [CA] 27.29 or carcinoembryonic antigen [CEA]) > 2 x upper limit
of normal (ULN), Circulating tumor cell assay > 5, or FDG-PET SUV > 2.5 in purely
lytic lesions; elevated tumor markers alone are insufficient

- No prior endocrine therapy for breast cancer or

- Off adjuvant endocrine therapy for > 6 months or

- Greater than 2 years of a single adjuvant endocrine therapy at the time of first
recurrence and plan to change to alternate endocrine therapy; use of tamoxifen
must be discontinued 6-8 weeks prior to entrance into the study

- Prior chemotherapy regimens in the adjuvant or neoadjuvant setting are allowed

- Women treated with adjuvant LHRH (luteinizing hormone-releasing hormone) analog are
eligible

- Be assessed for menopausal status; for study purposes, postmenopausal is defined as:

- A prior documented bilateral oophorectomy, or

- A history of at least 12 months without spontaneous menstrual bleeding, or

- Age 60 or older with a prior hysterectomy without oophorectomy, or

- Age less than 60 with a prior hysterectomy without oophorectomy (or in whom the
status of the ovaries is unknown), with a documented follicle stimulating hormone
(FSH) level demonstrating confirmatory elevation in the postmenopausal range for
the lab

- Premenopausal patients must have a baseline FSH, and estradiol levels to determine
menopausal status; measures will be repeated at 3-6 months to confirm menopausal
status

- Patients must be positive for estrogen receptor (ER) and may or may not be positive
for progesterone receptor (PgR) by IHC in the primary tumor and/or metastatic site;
the pathology report for assay of ER will be reviewed by one of the investigators
prior to enrollment, the study pathologist will review the pathology report if
necessary for determination of study eligibility

- Tumor HER2/neu expression must be determined prior to study enrollment; assessment may
be by fluorescence in situ hybridization (FISH) assay or by immunohistochemistry
(ICC); if determination is intermediate by ICC, FISH must be performed

- Life expectancy > 16 weeks

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

- Absolute neutrophil count (ANC) >= 1,000

- Platelet count >= 50,000

- Hemoglobin within normal limits (WNL) for the institution

- Serum creatinine =< 1.5 x institutional ULN (IULN) and estimated creatinine clearance
> 50 mL/min using the Cockroft-Gault formula

- Bilirubin =< 1.5 x ULN

- Serum glutamic oxaloacetic transaminase (SGOT)/ serum glutamic pyruvate transaminase
(SGPT) =< 1.5 x ULN

- Alkaline phosphatase =< 2.5 x ULN

- Patients must be planning a course of endocrine therapy with one of the following:
tamoxifen +/- ovarian suppression, aromatase inhibitor +/- fulvestrant (with ovarian
suppression in pre-menopausal patients) or fulvestrant alone

- After entry into the study, patients are expected to be followed for at least 6 months
after the injection of [^18F] FES

- Have a negative pregnancy test within 7 days prior to registration if of childbearing
potential

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer
from which the patient has been disease-free for 5 years

- Be informed of the investigational nature of this study and provide written informed
consent in accordance with institutional and federal guidelines prior to
study-specific screening procedures

- Women of child-bearing potential must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for the duration
of study participation; should a woman become pregnant or suspect she is pregnant
while participating in this study, she should inform her treating physician
immediately

Exclusion Criteria:

- Patients with a history of prior endocrine therapy for metastatic disease are NOT
eligible; adjuvant endocrine therapy for < 2 years total or discontinued less than 6
months before first disease recurrence also excludes the patient

- Patients with disease in the liver only are NOT eligible for the study

- Patients who are HER2/neu positive disease and planning to undergo HER2-directed
therapy (trastuzumab or lapatinib) are NOT eligible for the study

- Pregnant or lactating; women of childbearing potential with either a positive or no
pregnancy test at baseline are excluded

- Visceral crisis characterized by rapidly progressive hepatic or lymphangitic lung
metastases

- History of uncontrolled seizures, central nervous system disorders, or psychiatric
disability judged by the investigator to be clinically significant, precluding
informed consent

- Any other life-threatening illness (e.g., serious, uncontrolled concurrent infection
or clinically significant cardiac disease - congestive heart failure, symptomatic
coronary artery disease, cardiac arrhythmia not well controlled with medication)

- Unwillingness to give informed consent

- Medically unstable as judged by the patient's physician

- Psychological, familial, sociological, or geographical conditions which do not permit
compliance with the study protocol

- Patients with known allergic or hypersensitivity reactions to previously administered
radiopharmaceuticals; patients with significant drug or other allergies or autoimmune
diseases may be enrolled at the investigator's discretion

- Patient weight greater than 400 lbs (exceeds weight limit for tomograph table)

- Uncontrolled diabetes mellitus (fasting glucose > 200 mg/dL)

- Adult patients who require monitored anesthesia for PET scanning