Clinical trial NCT05183828: Effect of HSD3B1 (1245C) Gene Mutation on Treatment of Stage I-III Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
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
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2022-01-11
Enrollment: 68
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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.
* 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.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Changes in Ki67
timeFrame: Before (baseline) and up to 9 months after surgery
measure: Changes in Ki67
timeFrame: Before (baseline) and up to 9 months after surgery
measure: Changes in estrogen receptor (ER)alpha
timeFrame: Before (baseline) and up to 9 months after surgery
measure: Changes in estrogen receptor (ER)alpha
timeFrame: Before (baseline) and up to 9 months after surgery
measure: Changes in ER beta
timeFrame: Before (baseline) and up to 9 months after surgery
measure: Changes in ER beta
timeFrame: Before (baseline) and up to 9 months after surgery
measure: Effect of HSD3B1 (1245C) variant on changes in Ki67
timeFrame: Before (baseline) and up to 9 months after surgery
measure: Expression of 3betaHSD1
timeFrame: Up to 9 months after surgery
measure: Expression of intracellular androgen
timeFrame: Up to 9 months after surgery
measure: Expression of estrogen levels
timeFrame: Up to 9 months after surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Meghan R. Flanagan
role: PRINCIPAL_INVESTIGATOR
References: