Molecular Analyses to Predict Pathways of Endocrine Resistance Following Short Term Neoadjuvant Endocrine Treatment in Patients With Hormone Receptor-Positive HER2-negative Breast Cancer

NCT06361940 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRO00052561
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is an exploratory phase II interventional study that initiates standard-of-care anti-estrogen treatment preoperatively for 4-12 weeks (+/- 2 weeks).

Conditions

Breast Cancer

Keywords

hormone receptor-positive; HER2-negative; endocrine therapy; neoadjuvant; anastrozole; letrozole; exemestane; tamoxifen

Outcome Measures

Primary Outcomes (4)

• Change from baseline in the number of subjects with increased HER-1 receptor tyrosine kinases protein expression in tumors.

  Pathologists will use immunohistochemistry (IHC) to determine the average count of tumor protein expression. IHC is reported categorically as 0,1, 2 or 3. Any increase between these categories is considered increase.

  Time of surgery

• Change from baseline in the number of subjects with increased HER-2 receptor tyrosine kinases protein expression in tumors.

  Pathologists will use immunohistochemistry to determine the average count of tumor protein expression. IHC is reported categorically as 0,1,2 or 3. Any increase between these categories is considered increase.

  Time of surgery

• Change from baseline in the number of subjects with increased HER-3 receptor tyrosine kinases protein expression in tumors.

  Pathologists will use immunohistochemistry to determine the average count of tumor protein expression. IHC is reported categorically as 0,1,2 or 3. Any increase between these categories is considered increase.

  Time of surgery

• Change from baseline in the number of subjects with increased HER-4 receptor tyrosine kinases protein expression in tumors.

  Pathologists will use immunohistochemistry to determine the average count of tumor protein expression. IHC is reported categorically as 0,1,2 or 3. Any increase between these categories is considered increase.

  Time of surgery

Study Arms (1)

Standard-of-care Endocrine therapy

EXPERIMENTAL

Once enrolled, patients would be treated with the current standard-of-care endocrine therapy.

Drug: Aromatase inhibitors or tamoxifen

Interventions

Aromatase inhibitors or tamoxifen DRUG

Choice of endocrine therapy (aromatase inhibitors or tamoxifen) would be decided by medical oncologist, following a review of the patient's medical history and menstrual status.

Standard-of-care Endocrine therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unilateral diagnostic breast mammogram and ultrasound within 60 days of enrollment.
• Pathologically proven diagnosis of invasive breast cancer, clinical stage I or II.
• Patients must be clinically lymph node negative. Lymph node negativity must be confirmed by clinical exam and/or ultrasound imaging.
• The patient must be female.
• Age ≥18 years.
• Estrogen and/or progesterone receptor positive tumor defined ≥1% positively staining cells by immunohistochemistry, according to the current American Society of Clinical Oncology/College of American Pathologists guidelines.
• Human epidermal growth factor receptor 2 (HER2) /neu must be negative by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Bilateral breast cancer and/or multifocal, multicentric disease is allowed.
• Appropriate pretreatment evaluations for protocol entry, including no clinical evidence for distant metastases, based upon the following minimum diagnostic workup: history/physical examination, including breast exam (inspection and palpation of the breasts), clinically negative axillary lymph nodes, within 28 days prior to study entry.
• The patient must qualify for endocrine treatment (treatment of choice), per the treating medical oncologist.
• The patient must provide study-specific informed consent prior to study entry.
• Patients with a prior history of breast cancer will be considered eligible, if they have completed all treatment (including endocrine therapy) more than two years prior to registration.
• Patients must not have had a prior treatment for this breast cancer or for any malignancy diagnosed or treated within the past two years, with the exception of non-melanomatous skin cancer, carcinoma in situ of the cervix.
• Women of childbearing age will be advised to use adequate methods of contraception. Adequate methods of contraception for premenopausal women include barrier methods and/or non-hormonal methods (Intrauterine devices etc.).

You may not qualify if:

• American Joint Committee on Cancer (AJCC) clinical T4, N1-3 or M1, breast cancer.
• Synchronous non-breast malignancy (exceptions include non-melanomatous skin cancer, carcinoma in situ of the cervix).
• Purely noninvasive breast cancer (i.e., ductal carcinoma in situ, lobular carcinoma in situ).
• Men with breast cancer. Male breast cancer is a rare event and it is unclear if neoadjuvant endocrine treatment approach is safe in men.
• Medical, psychiatric or other condition that would prevent the patient from receiving the protocol therapy or providing informed consent.
• Pregnant or lactating women are ineligible.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Aromatase Inhibitors; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Lubna N Chaudhary, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505; cccto@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 8, 2024
• First Posted: April 12, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)