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