Anatomic Stage I Breast Cancer AJCC v8Phase 4NCT05183828
Effect of HSD3B1 (1245C) Gene Mutation on Treatment of Stage I-III Breast Cancer
A Phase 4 study testing Biospecimen Collection, Letrozole and Questionnaire Administration in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage II Breast Cancer AJCC v8, run by University of Washington at 1 site in United States.
Trial summary
This stage IV trial examines how a mutation in HSD3B1 (1245C) gene affects treatment of stage I-III breast cancer. This trial may help researchers determine if mutations in HSD3B1 decreases the efficacy of aromatase inhibitor therapy such as letrozole. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8
- What is being tested?
- Biospecimen Collection, Letrozole and Questionnaire Administration
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jan 2022to 13 May 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must be female age >= 18 years.
- Postmenopausal as defined by at least one of the following:
- Age >= 60 years;
- Age < 60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; or serum estradiol and follicle stimulating hormone levels within the local laboratory's normal reference range for postmenopausal females;
- Documented bilateral oophorectomy.
- Histologically confirmed diagnosis of carcinoma of the breast, clinical stage I-III.
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- Minimum tumor diameter of 1.0 cm as assessed by palpation or imaging (e.g., ultrasound) and with enough tumor left after the initial diagnostic biopsy to provide tumor tissue during the planned tumor resection.
- Candidate for surgical resection.
- ER+ breast cancer (> 1% positive stained cells) based on the most recent tumor biopsy documented by a local laboratory or medical record.
- Ki67 >= 10%.
- HER2-negative breast cancer based on the most recent tumor biopsy and documented by a local laboratory or medical record. HER2-negative tumor is defined per American Society of Clinical Oncology and the College of American Pathologists guidelines, 2018.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Prior use of hormone contraceptives and replacement therapy is allowed (e.g., estrogen and/or progestin) if discontinued > 6 months prior to diagnosis. Vaginal preparations are allowed.
- Ability to take oral medication and be willing to adhere to the study intervention.
Who cannot join
- Pre-treatment tumor biopsy sample not likely to provide adequate tissue sections for biomarker assays.
- Inoperable or metastatic disease.
- Subjects who have received any prior therapy for breast cancer, including radiotherapy, surgery, and cytotoxic and endocrine treatments.
- The subject must not have had hormonal therapy for breast cancer treatment or for breast cancer prevention within 1 year prior to study enrollment. (Note: Synchronous breast, cancer (including bilateral breast cancer) at separate sites is permissible, provided the patient does not receive medical treatments for breast cancer or radiation therapy to the ipsilateral breast during the study intervention period.
- Subjects with plans to undergo neoadjuvant chemotherapy.
- Use of hormonal contraceptives within 6 months of diagnosis.
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- Treatment with another investigational drug or other intervention within 28 days before the first administration of letrozole.
- History of allergic reactions/hypersensitivity attributed to compounds of similar chemical or biologic composition to letrozole or any ingredients.
- Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: Association of HSD3B1 Genotype With Response to Preoperative Letrozole Therapy Among Postmenopausal Women With Estrogen-Receptor Positive (ER+) HER2/Neu-Negative (HER2-) Invasive Carcinomas of the Breast
This stage IV trial examines how a mutation in HSD3B1 (1245C) gene affects treatment of stage I-III breast cancer. This trial may help researchers determine if mutations in HSD3B1 decreases the efficacy of aromatase inhibitor therapy such as letrozole. Letrozole may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
OUTLINE:
Patients receive letrozole orally (PO) once daily (QD) for 21 days in the absence of disease progression or unacceptable toxicity. If tumor resection occurs before or after day 22, letrozole administration must occur for a minimum of 14 days and a maximum of 70 days of total treatment. Patients also undergo collection of saliva samples.
- Conditions
- Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Breast Adenocarcinoma, Invasive Breast Carcinoma of No Special Type
- Being tested
- Biospecimen Collection, Letrozole, Questionnaire Administration
- Medical subject headings
- Carcinoma, Ductal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of saliva samples
LetrozoleDrug
Also called CGS 20267, Femara
Given PO
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (letrozole) | Experimental | Patients receive letrozole PO QD for 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of saliva samples. If tumor resection occurs before or after day 22, letrozole administration must occur for a minimum of 14 days and a maximum of 70 days of total treatment. Receives: Procedure: Biospecimen Collection; Drug: Letrozole; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Ki67
Will be assessed according to germline status.
Measured: Before (baseline) and up to 9 months after surgery
Changes in Ki67
Will be assessed according to somatic HSD3B1 (1245C) variant status.
Measured: Before (baseline) and up to 9 months after surgery
Changes in estrogen receptor (ER)alpha
Will be assessed according to germline status.
Measured: Before (baseline) and up to 9 months after surgery
Changes in estrogen receptor (ER)alpha
Will be assessed according to somatic HSD3B1 (1245C) variant status.
Measured: Before (baseline) and up to 9 months after surgery
Changes in ER beta
Will be assessed according to germline status.
Measured: Before (baseline) and up to 9 months after surgery
Changes in ER beta
Will be assessed according to somatic HSD3B1 (1245C) variant status.
Measured: Before (baseline) and up to 9 months after surgery
Effect of HSD3B1 (1245C) variant on changes in Ki67
Will evaluate whether androgen receptor (AR)+ modifies the effect of HSD3B1 (1245C) variant on changes in Ki67 before and after preoperative letrozole treatment, and whether this effects ER- and AR- gene expression signatures.
Measured: Before (baseline) and up to 9 months after surgery
Expression of 3betaHSD1
Will compare expression of 3betaHSD1 according to HSD3B1 allele status.
Measured: Up to 9 months after surgery
Expression of intracellular androgen
Will compare expression of intracellular androgen according to HSD3B1 allele status.
Measured: Up to 9 months after surgery
Expression of estrogen levels
Will compare expression of estrogen levels according to HSD3B1 allele status.
Measured: Up to 9 months after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2022
- Study start23 Jan 2022
- Primary completion13 May 2026
- Study completion13 May 2026
Why it stopped: Study ended earlier than anticipated due to end of funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anatomic Stage I Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by University of WashingtonThe 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Meghan R. Flanagan, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05183828
- Sponsor's protocol ID
- RG1121659
- Other IDs
- NCI-2021-12428, IR10794, P30CA015704
- Status last verified
- Jun 2026
- First submitted
- 9 Dec 2021
- Last updated
- 4 Jun 2026
- Results posted
- No
- 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 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association of HSD3B1 Genotype With Response to Preoperative Letrozole Therapy Among Postmenopausal Women With Estrogen-Receptor Positive (ER+) HER2/Neu-Negative (HER2-) Invasive Carcinomas of the Breast
- ClinicalTrials.gov ID
- NCT05183828
- Acronym / sponsor ID
- RG1121659
- Conditions
- Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Breast Adenocarcinoma, Invasive Breast Carcinoma of No Special Type
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study ended earlier than anticipated due to end of funding.
- Enrolment
- 62 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 23 Jan 2022 (actual)
- Primary completion
- 13 May 2026 (actual)
- Study completion
- 13 May 2026 (actual)
- First posted
- 11 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This stage IV trial examines how a mutation in HSD3B1 (1245C) gene affects treatment of stage I-III breast cancer. This trial may help researchers determine if mutations in HSD3B1 decreases the efficacy of aromatase inhibitor therapy such as letrozole. Letrozole may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed description
OUTLINE:
Patients receive letrozole orally (PO) once daily (QD) for 21 days in the absence of disease progression or unacceptable toxicity. If tumor resection occurs before or after day 22, letrozole administration must occur for a minimum of 14 days and a maximum of 70 days of total treatment. Patients also undergo collection of saliva samples.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (letrozole) | Experimental | Procedure: Biospecimen Collection, Drug: Letrozole, Other: Questionnaire AdministrationPatients receive letrozole PO QD for 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of saliva samples. If tumor resection occurs before or after day 22, letrozole administration must occur for a minimum of 14 days and a maximum of 70 days of total treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Subject must be female age >= 18 years.
- Postmenopausal as defined by at least one of the following:
- Histologically confirmed diagnosis of carcinoma of the breast, clinical stage I-III.
- Minimum tumor diameter of 1.0 cm as assessed by palpation or imaging (e.g., ultrasound) and with enough tumor left after the initial diagnostic biopsy to provide tumor tissue during the planned tumor resection.
- Candidate for surgical resection.
Key exclusion criteria (9 listed)
- Pre-treatment tumor biopsy sample not likely to provide adequate tissue sections for biomarker assays.
- Inoperable or metastatic disease.
- Subjects who have received any prior therapy for breast cancer, including radiotherapy, surgery, and cytotoxic and endocrine treatments.
- The subject must not have had hormonal therapy for breast cancer treatment or for breast cancer prevention within 1 year prior to study enrollment. (Note: Synchronous breast, cancer (including bilateral breast cancer) at separate sites is permissible, provided the patient does not receive medical treatments for breast cancer or radiation therapy to the ipsilateral breast during the study intervention period.
- Subjects with plans to undergo neoadjuvant chemotherapy.
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 |
|---|---|---|
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo collection of saliva samples | Procedure or surgery | Treatment (letrozole) |
| LetrozoleAlso: CGS 20267, FemaraGiven PO | Drug | Treatment (letrozole) |
| Questionnaire AdministrationAncillary studies | Other | Treatment (letrozole) |
Primary outcome
Changes in Ki67
Time frame: Before (baseline) and up to 9 months after surgery
Will be assessed according to germline status.
Changes in Ki67
Time frame: Before (baseline) and up to 9 months after surgery
Will be assessed according to somatic HSD3B1 (1245C) variant status.
Changes in estrogen receptor (ER)alpha
Time frame: Before (baseline) and up to 9 months after surgery
Will be assessed according to germline status.
Changes in estrogen receptor (ER)alpha
Time frame: Before (baseline) and up to 9 months after surgery
Will be assessed according to somatic HSD3B1 (1245C) variant status.
Changes in ER beta
Time frame: Before (baseline) and up to 9 months after surgery
Will be assessed according to germline status.
Changes in ER beta
Time frame: Before (baseline) and up to 9 months after surgery
Will be assessed according to somatic HSD3B1 (1245C) variant status.
Effect of HSD3B1 (1245C) variant on changes in Ki67
Time frame: Before (baseline) and up to 9 months after surgery
Will evaluate whether androgen receptor (AR)+ modifies the effect of HSD3B1 (1245C) variant on changes in Ki67 before and after preoperative letrozole treatment, and whether this effects ER- and AR- gene expression signatures.
Expression of 3betaHSD1
Time frame: Up to 9 months after surgery
Will compare expression of 3betaHSD1 according to HSD3B1 allele status.
Expression of intracellular androgen
Time frame: Up to 9 months after surgery
Will compare expression of intracellular androgen according to HSD3B1 allele status.
Expression of estrogen levels
Time frame: Up to 9 months after surgery
Will compare expression of estrogen levels according to HSD3B1 allele status.
Results and safety
The study was stopped early (reason given: Study ended earlier than anticipated due to end of funding.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- 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.
Meghan R. Flanagan principal investigator
Fred Hutch/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Biospecimen Collection, Letrozole and Questionnaire Administration in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage II Breast Cancer AJCC v8, run by University of Washington at 1 site 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 14 inclusion and 9 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 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study ended earlier than anticipated due to end of funding.). Results are not available in the source record.
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?
Changes in Ki67 (time frame: Before (baseline) and up to 9 months after surgery). The study lists 10 primary outcomes in all. 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 4 Jun 2026.