Trial Information

The Ultrasound Study of Tamoxifen

Elevated breast density is one of the strongest risk factors for non-familial breast cancer
[1]. Recently, the International Breast Cancer Intervention Study-1 (IBIS-1) trial reported
that women whose mammographic density declined by 10% within 12-18 months of initiating
tamoxifen chemoprevention also had a marked reduction in cancer risk [2]; however,
preliminary data suggested that in 30% of patients, tamoxifen failed to lower density and
did not reduce cancer risk. Therefore, we hypothesize that breast density represents a
biosensor of tamoxifen response, reflecting bioavailability and action of active drug
metabolites. Distinguishing tamoxifen responders from non-responders at the earliest time
point would have value for making informed treatment decisions, providing a rationale for
continued therapy among responders while sparing non-responders exposure to ineffective
treatment. We propose to use a novel ultrasound tomography (UST) scanner to repeatedly
assess volumetric breast density among 150 women during their first year of tamoxifen use
for clinical indications, including a referral from a health professional based on a woman's
personal risk of breast cancer or a diagnosis of atypical lobular or ductal hyperplasia
(ALH/ADH), ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), or invasive
breast cancer, to assess whether tamoxifen-related declines in mammographic density found at
12 months can be identified earlier with UST. UST is ideally suited for this application
because it produces volumetric data and avoids artifacts secondary to breast compression and
exposure to potentially harmful ionizing radiation. For comparison, we will perform UST on a
group of 150 age-, race-, and menopausal status-matched women without breast cancer in order
to assess changes in UST density over time without tamoxifen exposure. The specific goal of
this project is to utilize UST to describe the early time course of volumetric breast
density change. The broader objective is to assess the concept of breast density as a
biosensor of tamoxifen response and UST as a useful tool for making this determination.