Recruiting
Phase 2

Tamoxifen

Sponsor:

National Cancer Institute (NCI)

Code:

NCT06184750

Conditions

Breast Atypical Ductal Hyperplasia

Breast Atypical Lobular Hyperplasia

Breast Carcinoma

Breast Ductal Carcinoma In Situ

Breast Lobular Carcinoma In Situ

Eligibility Criteria

Sex: Female

Age: 18 - 55

Healthy Volunteers: Not accepted

Interventions

Biopsy Procedure

Biospecimen Collection

Mammography

Questionnaire Administration

Tamoxifen

Study Details

Brief summary:

This phase II trial evaluates response-guided low-dose tamoxifen for reducing breast density in women who are at higher than average risk for breast cancer. Increasing breast density is a well established risk factor for breast cancer. Tamoxifen is a selective estrogen receptor modulator. It works by blocking the effects of the hormone estrogen in the breast. Tamoxifen has been shown to reduce breast density, even at reduced dosages, and is approved for the prevention of breast cancer.

Conditions

Breast Atypical Ductal Hyperplasia

Breast Atypical Lobular Hyperplasia

Breast Carcinoma

Breast Ductal Carcinoma In Situ

Breast Lobular Carcinoma In Situ

Study ID

NCT06184750

Start date

Sep 27, 2024

Status verified date

Jul, 2026

Completion date

Sep 30, 2028

Anticipated

Primary completion date

Mar 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 18 - 55

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Premenopausal women at the time of enrollment defined by any of the following:

  • Age under 50 years and regular menstruation (most recent period within the past 3 months)
  • Age under 50 years and continuous hormonal contraception use and at least one intact ovary
  • Women who are not postmenopausal based on serum hormone levels. Women with estradiol > 30 pg/mL and follicle-stimulating hormone (FSH) < 30 IU/mL are eligible
  • Women with any of the following:

  • A history of unilateral estrogen receptor (ER) positive ductal carcinoma in situ (DCIS) with local therapy completed (as determined by treating physician recommendation and patient acceptance) at least 1 month prior to study entry. (The untreated breast will be the study breast, for both imaging and optional biopsy)
  • Recent or prior lobular carcinoma in situ (LCIS), or any form of epithelial atypia, flat epithelial (FEA), atypical ductal hyperplasia (ADH), or atypical lobular hyperplasia (ALH)
  • Are risk eligible for preventive medication based on a five-year risk of 1.7% or greater, estimated with a validated model: the National Cancer Institute (NCI) Breast Cancer Risk Assessment Tool, Tyrer-Cusick, Breast Cancer Surveillance Consortium. If the Tyrer-Cuzick model is used a ten-year risk of 3.4% or greater is acceptable
  • Are tamoxifen-eligible by American Society of Clinical Oncology (ASCO) guidelines (>= 2-fold increased risk compared to peer if age >= 45 years, and >= 4-fold increased risk if age < 45 years)
  • A history of mantle radiotherapy
  • A moderate penetrance germline pathogenic variant
  • Participants ≥ 18 and ≤ 55 years old will be enrolled. Our trial objectives are not relevant to females under 18 years of age since breast cancer is extraordinarily rare in this age group, and there are no guidelines regarding use of tamoxifen in children, even if know to be at very high risk for breast cancer when older. Because no dosing or adverse event (AE) data are currently available on the use of tamoxifen in participants < 18 years of age
  • Human immunodeficiency virus (HIV)-infected patients are eligible to participate if they are on effective anti-retroviral therapy with undetectable viral load within the prior 6 months
  • Women with evidence of chronic hepatitis B virus (HBV) infection, are also eligible if the HBV viral load is undetectable; they may be on suppressive therapy, if indicated
  • Women with a history of hepatitis C virus (HCV) infection are eligible if treated and cured. For those who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Women with herpes simplex virus (HSV) infection are eligible if on chronic or as needed (due to a flare) suppressive antiviral therapy
  • Hormonal contraceptive users are eligible and should maintain the same hormonal contraceptive preparation throughout the duration of the trial. Changing hormonal contraception after enrollment for medical reasons is allowed
  • The effects of tamoxifen on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because tamoxifen is known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence; partner vasectomy) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Breast Imaging Reporting and Data System (BIRADS) 1 or 2. Women with BIRADS 3 findings that have been biopsied and shown to be benign or are stable at 6-months follow-up are allowed
  • Women who are factor V leiden carriers and have not had a blood clot are eligible, if approved by their treating physician

Exclusion Criteria:

  • BIRADS breast density category A
  • History of selective estrogen receptor modulator (SERM) use within the past 5 years unless:

  • Use was less than 6 months duration in the past 5 years and not used in the 1 year prior to enrollment OR
  • Use was no greater than 2 months duration in the past 1 year and not used in the 6 months prior to enrollment
  • History of invasive breast cancer
  • Prior bilateral mastectomy or breast augmentation surgery including breast implants. Prior bilateral excisional surgical biopsy, mastopexy (breast lift) or mammoplasty (breast reduction) is allowed, as long as > 1 year has passed since the procedure
  • Women with "mosaic mammographic screening views", i.e., whose larger breast size precludes being imaged within a single mammographic screening view
  • Current use of a strong CYP3A4 inducer or a strong CYP2D6 inhibitor unless willing and able to discontinue use at least 30 days prior to screening and switch to an alternative medication for the duration of participation, under the advice of their physician. If the physician believes the current medication cannot be replaced, the participant will not be eligible
  • Current use of Warfarin
  • Planning to become pregnant within the next two years. Potential study participants will be questioned about this and excluded if they are planning pregnancy over the next 20 months
  • History of thromboembolism, pulmonary embolism, thrombotic stroke, arterial thrombosis of the extremity or deep vein thrombosis. A history of superficial thrombophlebitis is allowed
  • History of uterine cancer or atypical uterine hyperplasia with uterus intact
  • Participants may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to tamoxifen
  • Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because tamoxifen a category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with tamoxifen. Breastfeeding should be discontinued if the mother is treated with tamoxifen
  • Women with known gene mutations associated with an increased risk for breast cancer such as BRCA1/2, CDH1, PALB2, PTEN, STK11, or P53
  • Current use of sex hormones (estrogen, progesterone, or androgens), unless part of hormonal contraception pills
  • Prior invasive cancer ≥ T1 (other than non-melanoma skin cancer), unless curatively treated, and all treatment was completed > 5 years prior to enrollment

Study Design

Enrollment

200 participants

Anticipated

Intervention Model

Single group

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

experimental: Prevention (tamoxifen)

Participants receive tamoxifen 5mg PO QD for 6 months. Participants with aDAR >= 10% on mammogram at 6 months continue receiving tamoxifen 5mg PO QD for 12 months. Participants with aDAR < 10% at 6 months are escalated to receive tamoxifen 10mg PO QD for 6 months. Participants with aDAR >= 10% after 6 months of tamoxifen 10mg continue receiving tamoxifen 10 mg PO QD for 6 months. Participants with aDAR < 10% after 6 months of tamoxifen 10mg are given the option of continuing tamoxifen 10mg or escalating to receive tamoxifen 20mg PO QD for 6 months. Participants undergo mammography and collection of blood samples at screening and on study. Participants may optionally undergo biopsy at screening and on study.

Interventions

Biopsy Procedure

Undergo biopsy

Biospecimen Collection

Undergo collection of blood samples

Mammography

Undergo mammography

Questionnaire Administration

Ancillary studies

Tamoxifen

Given PO

Primary outcome measure

  • Response at any time point [ Time Frame: Up to 18 months ]

Central Contacts and Locations

Locations

University of Arizona Cancer Center - Prevention Research Clinic

Recruiting

Tucson, Arizona, United States, 85719

Contacts

Sima Ehsani Chimeh

520-626-2873simaehsani@arizona.edu

Principal Investigator:

Sima Ehsani Chimeh

Northwestern University

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Seema A. Khan

312-503-4236s-khan2@northwestern.edu

Principal Investigator:

Seema A. Khan

University of Illinois College of Medicine - Chicago

Recruiting

Chicago, Illinois, United States, 60612

Contacts

Kent F. Hoskins

312-996-1581khoski@uic.edu

Principal Investigator:

Kent F. Hoskins

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Carol J. Fabian

913-588-7791cfabian@kumc.edu

Principal Investigator:

Carol J. Fabian

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Judy E. Garber

617-632-3891judy_garber@dfci.harvard.edu

Principal Investigator:

Judy E. Garber

University of Michigan Rogel Cancer Center

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Melissa L. Pilewskie

734-647-8902mpilewsk@med.umich.edu

Principal Investigator:

Melissa L. Pilewskie

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Adetunji T. Toriola

314-286-2668a.toriola@wustl.edu

Principal Investigator:

Adetunji T. Toriola

Case Western Reserve University

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Amanda L. Amin

216-896-1787amanda.amin@uhhospitals.org

Principal Investigator:

Amanda L. Amin

Medical University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

Kevin S. Hughes

843-876-4420hughkevi@musc.edu

Principal Investigator:

Kevin S. Hughes

UT MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Parijatham (Priya) S. Thomas

713-792-6161psthomas@mdanderson.org

Principal Investigator:

Parijatham (Priya) S. Thomas

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Jul 27, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-07-27.