Impact of Low-dose Tamoxifen on BPU

Low-Dose Tamoxifen to Reduce High Background Parenchymal Uptake on Molecular Breast Imaging

The study will examine whether changes in background parenchymal uptake (BPU) on molecular breast imaging (MBI) can be induced by short-term use of low-dose tamoxifen. Women who have previously had high BPU on MBI will be recruited. Participants will take low-dose tamoxifen for a 30-day period, with post-tamoxifen MBI in order to investigate the impact of tamoxifen on BPU.

Study Overview

• Status: Completed
• Conditions: High Background Uptake on MBI
• Intervention / Treatment: Drug: Tamoxifen

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:The following are requirements for entry into the study:

1. Female, age 40 or older at the time of enrollment
2. Most recent MBI examination, performed within 3 years of enrollment, showed moderate or marked background parenchymal uptake
3. Mammogram performed within 12 months prior to enrollment that is available for comparison
4. Willing and able to return for MBI following 30 days of low-dose tamoxifen

5. If able to become pregnant

   1. Negative pregnancy test within 48 hours prior to study MBI exam(s)
   2. Agrees to avoid pregnancy during the study and for at least 2 months after study participation ends, by abstinence, barrier method, or nonhormonal contraception.

6. Understands and signs the consent form

   -

Exclusion Criteria:Subjects will be excluded if any of the following characteristics are present:

1) Evidence of suspected breast disease as defined by positive findings or recommendation for short-interval follow-up on most recent breast imaging (including mammography, MBI, MRI, ultrasound, etc.) not yet resolved prior to enrollment 2) Breast biopsy or breast surgery performed 6 months prior to enrollment 3) Bilateral breast implants or status post-bilateral prophylactic mastectomy 4) Pregnant or lactating 5) Current or recent use (within 6 months prior to enrollment) of any of the following drugs:

1. Systemic hormonal therapy (oral or transdermal patch formulations)
2. Hormonal contraception (oral, transdermal, implanted, or injected formulations)
3. Selective estrogen receptor modulators (tamoxifen, raloxifene, or toremifene)
4. Aromatase inhibitors (anastrazole, letrozole, or exemestane)
5. GnRH analogs
6. Prolactin inhibitors
7. Androgens or antiandrogens
8. Anticoagulants or "blood thinners" (warfarin, heparin, rivaroxaban and other novel anticoagulants)

9. Drugs known to be strong inhibitors of CYP2D6, the major P450 enzyme that metabolizes tamoxifen, including:

   • bupropion (Wellbutrin)
   • fluoxetine (Prozac)
   • paroxetine (Paxil)
   • quinidine (Quinidex) 6) Personal history of any type of malignancy, with the exclusion of non-melanoma skin cancer, diagnosed prior to enrollment 7) Personal history or strong family history of blood clots in legs or lungs (also known as deep vein thrombosis or pulmonary embolism) 8) Personal history of transient ischemic attack (TIA) or cerebrovascular accident (CVA) 9) Active proliferative disorders of the endometrium such as atypical hyperplasia, history of active endometriosis, unresected polyps 10) Any type of retinal disorders or severe cataract 11) Current or former smoker 12) Known carrier of BRCA1 or BRCA2 genetic mutation or known DNA repair defect.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tamoxifen 5 mg/day; Women with high background uptake on MBI take 5 mg tam per day for 30 days.	Drug: Tamoxifen; 5 mg or 10 mg tamoxifen per day for 30 days.
Experimental: Tamoxifen 10 mg/day; Women with high background uptake on MBI take 10 mg tam per day for 30 days.	Drug: Tamoxifen; 5 mg or 10 mg tamoxifen per day for 30 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Background Parenchymal Uptake (BPU) on Molecular Breast Imaging (MBI)	An image analysis tool to obtain a quantitative measure of background parenchymal uptake (BPU) was applied to pre-tamoxifen and post-tamoxifen MBI exams. The percent change in BPU from pre-tamoxifen to post-tamoxifen MBI was determined.	30 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Carrie Hruska, PhD R-D, Mayo Clinic

Publications and helpful links

General Publications

• Hruska CB, Hunt KN, Conners AL, Geske JR, Brandt KR, Degnim AC, Vachon CM, O'Connor MK, Rhodes DJ. Impact of short-term low-dose tamoxifen on molecular breast imaging background parenchymal uptake: a pilot study. Breast Cancer Res. 2019 Mar 8;21(1):38. doi: 10.1186/s13058-019-1120-5.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): February 25, 2018
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: November 29, 2016
• First Submitted That Met QC Criteria: November 30, 2016
• First Posted (Estimate): December 1, 2016

Study Record Updates

• Last Update Posted (Actual): July 16, 2019
• Last Update Submitted That Met QC Criteria: April 29, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen
• Other Study ID Numbers: IRB 16-008736

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No