Breast Atypical HyperplasiaPhase 2NCT04570956
Oral Tamoxifen vs. TamGel vs. Control in Women With Atypical Hyperplasia, Lobular Carcinoma In Situ, or Increased Breast Cancer Risk
A Phase 2 study testing Tamoxifen, Topical 4-OHT( 4-hydroxytamoxifen)gel 4 mg/each breast/day and Questionnaire Administration in people with Breast Atypical Hyperplasia and Breast Lobular Carcinoma in Situ, run by Mayo Clinic at 3 sites in United States.
Trial summary
The investigators plan to prospectively study breast tissue changes after a short course of Tamoxifen (Tam). Read more about this study
- Who is it for?
- Ages 18 to 80 years, women only
- Conditions the study is for
- Breast Atypical Hyperplasia, Breast Lobular Carcinoma in Situ, Breast Atypical Lobular Hyperplasia
- What is being tested?
- Tamoxifen, Topical 4-OHT( 4-hydroxytamoxifen)gel 4 mg/each breast/day and Questionnaire Administration
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 3 sitesUnited States
- Study dates
- 26 Jul 2021to 15 Oct 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing to return to enrolling institution for follow-up
- Willing to complete required testing
- Ability to complete questionnaire by themselves or with assistance
- Female (sex that was assigned at birth)
- Ipsilateral intact breast with histology confirmation of atypical ductal or lobular hyperplasia, or lobular carcinoma in situ (LCIS), within the last 12 months, whether surgically excised or not.; OR neither AH nor LCIS but increased breast cancer risk defined as either:
- Gail model (Breast Cancer Risk Assessment Tool) 5 year breast cancer risk of >= 3%, or
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- International Breast Intervention Study model 10 year breast cancer risk of >= 5%.
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- The effects of topical afimoxifene (4-OHT) gel on the developing human fetus at the recommended therapeutic dose are unknown. However, oral tamoxifen is Pregnancy Category D-positive evidence of human fetal risk. For this reason, and because triphenylethylene antiestrogens, including tamoxifen, are known to be teratogenic, women of childbearing potential and their male partners must agree to use at least one effective form of birth control (abstinence is not an allowed method) prior to study entry and for the duration of study participation, and for 2 months following the last dose of study medications (participant can resume oral birth control pills for effective birth control measures after post-treatment biopsy is done). Effective birth control methods during treatment are: copper and Mirena intrauterine device (IUD), diaphragm/cervical cap/shield, spermicide, contraceptive sponge, condoms. Tubal Ligation is an acceptable method of birth control. Women of childbearing potential must have a negative pregnancy test within five days before starting study medications. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
- Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of the study.
- Participants must have acceptable organ and marrow function as judged by treating physician's evaluation of baseline laboratory data.
- Negative pregnancy (serum or urine) test if of childbearing potential and/or follicle stimulating hormone (FSH) to verify menopausal status.
Who cannot join
- Clinically suspicious mass/lesions
- Breast cancer in the past 5 years.
- Patients with any history of venous thromboembolic disease, regardless of timeframe (history of varicose veins and superficial phlebitis is allowed).
- Current pregnancy or lactation.
- History of other prior breast cancer-specific therapy within the previous 2 years (chemotherapy, anti-HER2 agents, endocrine agents, everolimus, CDK4-6 inhibitors).
- Cytotoxic chemotherapy for any indication in last 2 years.
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- Prior use of selective estrogen receptor modulator (SERMS) or AIs including tamoxifen, raloxifene, anastrozole, letrozole, or exemestane for prevention or therapy 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.
- Exogenous sex steroid, including oral contraceptive pill use within 1 month prior to pretreatment breast biopsy. Use of vaginally administered estrogens and hormone coated IUD such as Mirena is permitted.
- History of any prior ipsilateral breast radiotherapy. Previous unilateral radiation of the contralateral side is allowed.
- Skin lesions on the breast that disrupt the stratum corneum (e.g., eczema, ulceration).
- History of endometrial neoplasia
- Current smoker. Cessation for at least 6 weeks
- Current users of potent inhibitors of tamoxifen metabolism. The potent inhibitors of tamoxifen metabolism are: bupropion, cinacalcet, fluoxetine, paroxetine, quinidine.
- Participants may not be receiving any other investigational agents within 90 days of enrollment or during this study.
- History of allergic reactions to tamoxifen.
- Uncontrolled intercurrent illness that in the judgement of the treating physician would make them unsuitable for study participation
- Current use of anticoagulation medications.
- Patients who are breastfeeding.
- Hemoglobin < 10 g/dL (within 30 days of randomization).
- Leukocytes < 3,000/microliter (within 30 days of randomization).
- Platelets < 100,000/microliter (within 30 days of randomization).
- Total bilirubin > 1.5 x institutional upper limit of normal (ULN) (within 30 days of randomization).
- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) > 1.5 x ULN (within 30 days of randomization).
- Alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) > 1.5 x ULN (within 30 days of randomization).
- Alkaline phosphatase, S > 1.5 x ULN (within 30 days of randomization).
- Albumin, S > 1.5 x ULN (within 30 days of randomization).
- Protein, total, S > 1.5 x ULN (within 30 days of randomization).
- Creatinine > 1.5 x ULN (within 30 days of randomization).
- Antithrombin III <80% of normal.
- Fibrinogen >1000 mg/dL.
- Patients who are taking any medications, herbal products, or over the counter (OTC) products that are moderate or strong CYP2D6 inhibitors or CYP3A inducers. Patients should also refrain from starting any drug or product with these properties during the study. This is to avoid any potential interactions with tamoxifen or 4-OHT.
- Clinically significant arrhythmia requiring ongoing medication for control / treatment, especially those with high risk of QT prolonging effects.
- Identification of a clinically suspicious mass on examination.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
MD Anderson Cancer center at Cooper
Camden, New Jersey, 08103
Northwestern University
Evanston, Illinois, 60208
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: Phase IIB Randomized Trial of Oral Tamoxifen vs. Topical 4-hydroxytamoxifen Gel vs. Control in Women With Atypical Hyperplasia, Lobular Carcinoma in Situ, or Increased Breast Cancer Risk
The investigators plan to prospectively study breast tissue changes after a short course of Tamoxifen (Tam).
Read the detailed description
Women with atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) are at increased risk of breast cancer (BC) (~1-2 % per year). Over two decades ago, placebo-controlled randomized trials established that oral tamoxifen (20 mg/day) reduces breast cancer risk by 50% in generally defined high risk women, with ~70% reduction in women at high risk specifically due to atypical hyperplasia.[1] Years later, the side effects and toxicity of oral tamoxifen at 20 mg/day remain a significant barrier to its uptake and longterm compliance.[2, 3] To address the issue of toxicity, two main strategies have been pursued: 1) using a lower dose of oral tamoxifen, and 2) using a topical formulation of tamoxifen to avoid systemic side effects. The investigators will perform a prospective study of women with AH or LCIS who will take a short course of prevention therapy; breast tissue samples will be evaluated pre- and post-therapy to identify and evaluate very early biomarkers of response. The overall goal of the study is to evaluate short-term changes in background breast tissue induced by either low-dose oral tamoxifen or topical 4-OHT gel in women with AH or LCIS.
- Conditions
- Breast Atypical Hyperplasia, Breast Lobular Carcinoma in Situ, Breast Atypical Lobular Hyperplasia, Breast Carcinoma
- Being tested
- Tamoxifen, Topical 4-OHT( 4-hydroxytamoxifen)gel 4 mg/each breast/day, Placebo, Questionnaire Administration
- Medical subject headings
- Breast Carcinoma In Situ, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TamoxifenDrug
Also called Oral tamoxifen
Oral Tamoxifen 10 mg/day
Topical 4-OHT( 4-hydroxytamoxifen)gel 4 mg/each breast/dayDrug
Also called Topical gel
Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day
PlaceboDrug
Also called placebo pill, placebo gel
placebo pill or placebo gel
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Oral Tamoxifen 10 mg/day | Experimental | Oral Tamoxifen 10 mg/day Receives: Drug: Tamoxifen; Other: Questionnaire Administration |
| Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day | Experimental | Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day
+oral placebo Receives: Drug: Topical 4-OHT( 4-hydroxytamoxifen)gel 4 mg/each breast/day; Other: Questionnaire Administration |
| Control | Experimental | Oral and gel placebo Receives: Drug: Placebo; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Median Lobular Ki67 From Pre-Tamoxifen Breast Biopsy to On-Tamoxifen Biopsy With 4 Weeks of Intervention
All patients received an oral pill and a topical gel. Prior to assessing non-inferiority of 4-OHT Gel compared to Oral Tamoxifen, treatment effect was assessed within each group by testing for a significant reduction in median lobular Ki67 between PreTam and OnTam biopsy. Median lobular Ki67 is assessed using the percentage of cells stained across all lobules separately at PreTam and OnTam timepoints, evaluated for a difference in median calculated change.
Measured: Pre-biopsy to post-biopsy following 4 weeks of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2020
- Study start26 Jul 2021
- Primary completion15 Oct 2024
- Study completion15 Oct 2024
Why it stopped: grant and funding expired
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast Atypical HyperplasiaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized 2:2:1 with either Oral Tamoxifen 10 mg/day * gel placebo, Topical 4-OHT gel 4 mg/each breast/day * oral placebo, or Control Oral and gel placebo for 4 weeks of treatment.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Amy Degnim, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04570956
- Sponsor's protocol ID
- CA237607
- Other IDs
- 5R01CA237607-05, 19-011444
- Status last verified
- Aug 2026
- First submitted
- 28 Sep 2020
- Last updated
- 24 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIB Randomized Trial of Oral Tamoxifen vs. Topical 4-hydroxytamoxifen Gel vs. Control in Women With Atypical Hyperplasia, Lobular Carcinoma in Situ, or Increased Breast Cancer Risk
- ClinicalTrials.gov ID
- NCT04570956
- Acronym / sponsor ID
- CA237607
- Conditions
- Breast Atypical Hyperplasia, Breast Lobular Carcinoma in Situ, Breast Atypical Lobular Hyperplasia, Breast Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: grant and funding expired
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 26 Jul 2021 (actual)
- Primary completion
- 15 Oct 2024 (actual)
- Study completion
- 15 Oct 2024 (actual)
- First posted
- 30 Sep 2020 (actual)
- Results
- Posted 1 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators plan to prospectively study breast tissue changes after a short course of Tamoxifen (Tam).
Detailed description
Women with atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) are at increased risk of breast cancer (BC) (~1-2 % per year). Over two decades ago, placebo-controlled randomized trials established that oral tamoxifen (20 mg/day) reduces breast cancer risk by 50% in generally defined high risk women, with ~70% reduction in women at high risk specifically due to atypical hyperplasia.[1] Years later, the side effects and toxicity of oral tamoxifen at 20 mg/day remain a significant barrier to its uptake and longterm compliance.[2, 3] To address the issue of toxicity, two main strategies have been pursued: 1) using a lower dose of oral tamoxifen, and 2) using a topical formulation of tamoxifen to avoid systemic side effects. The investigators will perform a prospective study of women with AH or LCIS who will take a short course of prevention therapy; breast tissue samples will be evaluated pre- and post-therapy to identify and evaluate very early biomarkers of response. The overall goal of the study is to evaluate short-term changes in background breast tissue induced by either low-dose oral tamoxifen or topical 4-OHT gel in women with AH or LCIS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- Subjects will be randomized 2:2:1 with either Oral Tamoxifen 10 mg/day * gel placebo, Topical 4-OHT gel 4 mg/each breast/day * oral placebo, or Control Oral and gel placebo for 4 weeks of treatment.
| Arm | Type | Receives |
|---|---|---|
| Oral Tamoxifen 10 mg/day | Experimental | Drug: Tamoxifen, Other: Questionnaire AdministrationOral Tamoxifen 10 mg/day |
| Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day | Experimental | Drug: Topical 4-OHT( 4-hydroxytamoxifen)gel 4 mg/each breast/day, Other: Questionnaire AdministrationTopical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day +oral placebo |
| Control | Experimental | Drug: Placebo, Other: Questionnaire AdministrationOral and gel placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Willing to return to enrolling institution for follow-up
- Willing to complete required testing
- Ability to complete questionnaire by themselves or with assistance
- Female (sex that was assigned at birth)
- Ipsilateral intact breast with histology confirmation of atypical ductal or lobular hyperplasia, or lobular carcinoma in situ (LCIS), within the last 12 months, whether surgically excised or not.; OR neither AH nor LCIS but increased breast cancer risk defined as either:
Key exclusion criteria (35 listed)
- Clinically suspicious mass/lesions
- Breast cancer in the past 5 years.
- Patients with any history of venous thromboembolic disease, regardless of timeframe (history of varicose veins and superficial phlebitis is allowed).
- Current pregnancy or lactation.
- History of other prior breast cancer-specific therapy within the previous 2 years (chemotherapy, anti-HER2 agents, endocrine agents, everolimus, CDK4-6 inhibitors).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TamoxifenAlso: Oral tamoxifenOral Tamoxifen 10 mg/day | Drug | Oral Tamoxifen 10 mg/day |
| Topical 4-OHT( 4-hydroxytamoxifen)gel 4 mg/each breast/dayAlso: Topical gelTopical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day | Drug | Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day |
| PlaceboAlso: placebo pill, placebo gelplacebo pill or placebo gel | Drug | Control |
| Questionnaire AdministrationAncillary studies | Other | Control, Oral Tamoxifen 10 mg/day, Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day |
Primary outcome
Change in Median Lobular Ki67 From Pre-Tamoxifen Breast Biopsy to On-Tamoxifen Biopsy With 4 Weeks of Intervention
Time frame: Pre-biopsy to post-biopsy following 4 weeks of intervention
All patients received an oral pill and a topical gel. Prior to assessing non-inferiority of 4-OHT Gel compared to Oral Tamoxifen, treatment effect was assessed within each group by testing for a significant reduction in median lobular Ki67 between PreTam and OnTam biopsy. Median lobular Ki67 is assessed using the percentage of cells stained across all lobules separately at PreTam and OnTam timepoints, evaluated for a difference in median calculated change.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy Degnim, M.D. principal investigator
Mayo Clinic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tamoxifen, Topical 4-OHT( 4-hydroxytamoxifen)gel 4 mg/each breast/day and Questionnaire Administration in people with Breast Atypical Hyperplasia and Breast Lobular Carcinoma in Situ, run by Mayo Clinic at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Median Lobular Ki67 From Pre-Tamoxifen Breast Biopsy to On-Tamoxifen Biopsy With 4 Weeks of Intervention (time frame: Pre-biopsy to post-biopsy following 4 weeks of intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.