A Pilot Study of Letrozole for One Year in Women at Enhanced Risk of Developing Breast Cancer: Effects on Mammographic Density

Background: Tamoxifen or raloxifen for 5 years reduces the risk of developing invasive breast cancer by 40%. To address safety concerns and seek enhanced efficacy, studies of new chemopreventive agents using mammographic density as a surrogate end point are attractive. Patients and Methods: Postmenopausal women with risk factors for developing breast cancer were given letrozole 2.5 mg daily for one year, and mammographic density was the biomarker of breast cancer risk modification. It was assessed (blinded to the reader) at baseline, 6, and 12 months in 16 evaluable women among 20 enrolled. Results: Eight patients exhibited decreased mammographic density at six months, and eleven at 12 months. Toxicities included joint aches not precluding continued treatment. Conclusion: This pilot study supports the use of letrozole for reducing breast cancer risk. In addition, it encourages prospective studies of serial changes in mammographic density as a biomarker of risk modification within a selected high-risk population.