Letrozole in Treating Postmenopausal Women With Stage I, II or III Breast Cancer That Can Be Removed by Surgery

Vanderbilt University Medical Center

Status and phase

Terminated

Early Phase 1

Conditions

Breast Cancer

Treatments

Procedure: biopsy/lumpectomy/mastectomy

Drug: letrozole

Other: Blood Collection

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00651976

VU-VICC-IRB-080064

VICC BRE 0776

P50CA098131 (U.S. NIH Grant/Contract)

VU-VICC-BRE-0776

P30CA068485 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving letrozole before surgery allows us to monitor the effects of letrozole on the tumor on a molecular level and determine markers of response to treatment.

PURPOSE: This study will show us how well letrozole works in treating postmenopausal women with stage I, II or III breast cancer that can be removed by surgery.

Full description

OBJECTIVES:

Primary To determine that in breast tumors that continue to exhibit high proliferation (i.e., Ki67) upon hormone deprivation (with letrozole), their gene expression and/or a mutational or proteomic signatures will harbor molecules or 'pathways' that are biomarkers of resistance to endocrine therapy or a cause of it.

The ultimate goal of these aims is to identify clinically-targetable pathways which can be exploited to enhance responses and survival in patients with ER+ breast cancer.

OUTLINE: Patients receive oral letrozole once daily for 7-21 days in the absence of disease progression or unacceptable toxicity. Within 24 hours after the last dose of letrozole, patients undergo total mastectomy or segmental resection with lymph node evaluation.

Pre-treatment diagnostic breast tissue is obtained. Patients undergo treatment and then undergo standard of care mastectomy or lumpectomy. Pre and post treatment tumor tissue samples are analyzed for Ki67, P-ER, ER, progesterone receptor (PR), and caspase 3 by immunohistochemistry; and RNA microarray.

Enrollment

213 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Diagnosis of invasive breast cancer
- Clinical stage I, II, or III disease
- Resectable disease
Measurable disease, defined as a mass that can be reproducibly measured by physical examination and/or ultrasound and is at least 1 cm in size by ultrasound
- Patients with measurable residual tumor at the primary site allowed
Estrogen receptor-positive tumor by immunohistochemistry (IHC)
HER2-negative tumor by Herceptest (0 or +1) OR HER2 not overexpressed by fluorescence in situ hybridization (FISH)
Planning to undergo surgical treatment with either segmental resection or total mastectomy with or without lymph node evaluation
Must have core biopsies from the time of diagnosis available (may include sections of paraffin-embedded material)
Prior contralateral breast cancer allowed provided there is no evidence of recurrence of the initial primary breast cancer
Patients with locally advanced disease who are candidates for preoperative chemotherapy at the time of initial evaluation are not eligible
- Locally advanced disease is defined by any of the following:
  - Primary tumor ≥ 5 cm (T3)
  - Tumor of any size with direct extension to the chest wall or skin (T4a-c)
  - Inflammatory breast cancer (T4d)
  - Fixed axillary lymph node metastases (N2)
  - Metastasis to ipsilateral internal mammary node (N3)
No locally recurrent disease
No evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases)

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Postmenopausal, as defined by any of the following:
- 55 years of age and over
- Under 55 years of age and meets 1 of the following criteria:
  - Amenorrheic for at least 12 months
  - Follicle-stimulating hormone (FSH) ≥ 40 IU/L and estradiol levels ≤ 20 IU/L
- Has undergone prior bilateral oophorectomy or radiation castration AND has been amenorrheic for at least 6 months
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
SGOT and SGPT ≤ 1.5 times ULN
Creatinine ≤ 1.5 t times ULN
Able to swallow and retain oral medication
No serious medical illness that, in the judgment of the treating physician, places the patient at high risk for operative mortality
No malabsorption syndrome, ulcerative colitis, or other disease significantly affecting gastrointestinal function
No other malignancy within the past 5 years except for completely resected nonmelanoma skin cancer or successfully treated in situ carcinoma
No dementia, altered mental status, or any psychiatric condition that would preclude the understanding or rendering of informed consent
No severe uncontrolled malabsorption condition or disease (i.e., grade II/III diarrhea, severe malnutrition, or short gut syndrome)

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 21 days since prior tamoxifen or raloxifene as a preventive agent
At least 7 days since prior hormone replacement therapy (e.g., conjugated estrogens [Premarin])
No prior resection of the stomach or small bowel
More than 30 days or 5 half-lives, whichever is longer, since prior investigational drugs
No prior chemotherapy for this primary breast cancer
No other concurrent investigational agents
No other concurrent anticancer therapy (e.g., chemotherapy, radiotherapy, immunotherapy, hormonal therapy, or any other biologic therapy)