Phase I Dose-Finding Trial of Letrozole in Postmenopausal Women at High Risk for Breast Cancer

Inclusion Criteria:

- Healthy postmenopausal women at "high risk" for breast cancer will be eligible for
the study; definition of menopause will be:

- Amenorrhea for at least 12 months, or

- History of hysterectomy and bilateral salpingo-oophorectomy, or

- At least 55 years of age with prior hysterectomy with or without oophorectomy,
or

- Age 35 to 54 with a prior hysterectomy without oophorectomy OR with a status of
ovaries unknown with documented follicle-stimulating hormone level demonstrating
elevation in postmenopausal range

- "High risk" for breast cancer will be defined as:

- Prior histologically confirmed lobular carcinoma in situ (LCIS) treated by
local excision only, or

- At least 1.66% probability of invasive breast cancer within 5 years using
the Breast Cancer Risk Assessment Tool (http://www.cancer.gov/bcrisktool/)

- ECOG performance status 0 or 1 Karnofsky 80% or above

- Leukocytes >= 3,000/uL

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 100,000/uL

- Total bilirubin =< 2.0 mg/dL

- AST (SGOT)/ALT (SGPT) =< 2.0 X institutional ULN

- Creatinine =< 1 X institutional ULN

- Recent mammogram negative for breast cancer, BIRADS score < 3 (within the last 12
months)

- Ability to understand and the willingness to sign a written informed consent
document; only potential participants with the ability to understand and the
willingness to sign a written document will be presented with an informed consenting
document

Exclusion Criteria:

- Women diagnosed with osteoporosis (previously or on screening DEXA for this study)
and not on a stable dose of long or short-acting bisphosphonates therapy for at least
3 months will be excluded from the study; women diagnosed with osteoporosis and on
raloxifene (Evista) therapy will be excluded from the study; use of calcium and/or
vitamin D for osteoporosis prevention or treatment is allowed; women with osteopenia
will be allowed to participate in this study

- Have had invasive cancer within the past five years except non-melanoma skin cancer

- Evidence of suspicious of malignant disease on bilateral mammogram within the past
year unless ruled out by further evaluation

- History of prior invasive breast cancer or intraductal carcinoma in situ, or history
of prior radiation therapy to the chest or breast

- Participants may not be receiving any other investigational agents; participants may
not be concurrently enrolled in another breast cancer prevention intervention trial

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to letrozole

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Within 3 months since prior estrogen or progesterone replacement therapy, oral
contraceptives, androgens, luteinizing hormone-releasing hormone analogs, prolactin
inhibitors, or antiandrogens

- Within 3 months since prior tamoxifen, raloxifene, or other selective
estrogen-receptor modulators

- Within 3 months since regular use (more than 2 times a week) of prior estrogenic
supplements or herbal remedies

- History of bleeding or clotting disorder; current or recent (within 3 months) use of
Coumadin, Plavix or other systemic anticoagulant other than aspirin is not permitted
if subject chooses to participate in the optional RPFNA procedure; if a subject
chooses not to participate in the RPFNA procedure, prior or current treatment with
systemic anticoagulants is permitted