The Ultrasound Study of Tamoxifen
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms
Study type: Observational

Summary: 
      Background:

      - Studies have shown that changes in breast density (the amount of white area on a woman's
      mammogram) may be related to changes in breast cancer risk. Currently, there is no ideal way
      to measure breast density repeatedly over time. Researchers want to test whether ultrasound
      tomography scans can show changes in breast density. To examine these changes, healthy
      volunteers with no history of breast cancer and women who are taking tamoxifen will have
      ultrasound tomography scans.

      Objectives:

      - To test whether ultrasound tomography scans can show changes in breast density related to
      tamoxifen exposure.

      Eligibility:

      - Women between 30 and 70 years of age who are (a) taking tamoxifen or (b) healthy volunteers
      who have never had breast cancer.

      Design:

        -  All participants will have a screening visit. Healthy volunteers will have one
           additional study visit; women taking tamoxifen will have three additional study visits.

        -  All participants will be screened with a physical exam and medical history. They will
           also give blood and saliva samples. This visit will also include an initial ultrasound
           tomography breast scan.

        -  For the healthy volunteers:

        -  At the study visit (12 months after the screening visit), participants will have a short
           interview and be weighed. They will also have an ultrasound tomography breast scan and
           provide a blood sample.

        -  For the women taking tamoxifen:

        -  At the second and third visits (1 to 3 months and 3 to 6 months after starting
           tamoxifen), participants will have a short interview. They will also be weighed and have
           an ultrasound tomography breast scan.

        -  At the fourth visit (12 months after starting tamoxifen), participants will have a short
           interview, weight measurement, and the ultrasound tomography breast scan, and will also
           provide a blood sample.

        -  All participants may be followed for up to 5 years after their final study visit.
    

Detailed description: 
      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.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        primary clinical
      
Keywords: Ultrasound Tomography; Tamoxifen; Breast Cancer; Estrogen Receptor Positive; Breast Density