Study of Breast Cancer Prevention by Letrozole in High Risk Women

Study of Breast Cancer Prevention by Letrozole in High Risk Women

This is a multi-institution double-blind placebo-controlled trial whose main objective is to determine if 6 months of letrozole (2.5 mg daily) can reduce proliferation as assessed by Ki-67 in high risk postmenopausal women on systemic hormone replacement therapy who have random periareolar fine needle aspiration (RPFNA) evidence of hyperplasia with atypia or borderline atypia, and a minimum Ki-67 of >1.5%.

The primary hypothesis is that proliferation and expression of other estrogen response genes will be favorably modulated by six months of letrozole relative to placebo without substantially increasing hot flashes or worsening overall quality of life.

Subsequent to the 6 month RPFNA for assessment of biomarkers, toxicity and quality of life assessments, all women may receive optional open-label letrozole for an additional 6 months, followed by a third RPFNA and biomarker

Inclusion Criteria:

• Post-menopausal women at high risk for development of breast cancer
• stable dose of hormone replacement therapy
• have cytomorphologic evidence of hyperplasia +/- atypia and Ki-67 expression >1.5% in benign breast epithelial cells acquired by RPFNA
• Serum level of 25-hydroxyvitamin D of at least 30 ng/ml prior to study entry
• Willing to have a repeat random periareolar fine needle aspiration (RPFNA) and mammogram at 6 months and 12 months (if participating in the open label portion of the study) following initiation of study drug

Exclusion Criteria:

• Prior history of osteoporosis or osteoporotic fracture.
• Prior history of invasive breast cancer or other invasive cancer within five years from date of study entry.
• Current and chronic use of cyclooxygenase-2 (COX-2) specific inhibitors or NSAIDs
• Receiving treatment for rheumatoid arthritis or fibromyalgia
• Current history of poorly controlled migraines or perimenopausal symptoms
• Currently receiving other investigational agents.
• Receipt of more than 6 months of an aromatase inhibitor (anastrozole, exemestane, letrozole, etc.) at any time in the past.