Predicting Endocrine Resistance in Breast Cancer Treatment

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

This study is testing if giving hormone therapy before surgery can help doctors understand how well it works for women with a specific type of breast cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Medical College of Wisconsin (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Milwaukee, Wisconsin)
• Trial ID: NCT06361940 on ClinicalTrials.gov

What this trial studies

This exploratory phase II interventional study evaluates the effectiveness of preoperative endocrine therapy in patients with hormone receptor-positive, HER2-negative breast cancer. Participants will receive standard anti-estrogen treatment for 4-12 weeks before surgery, allowing researchers to assess tumor response while still in vivo. By analyzing molecular changes in the tumors before and after treatment, the study aims to identify predictors of treatment responsiveness and potential new therapeutic targets. This approach could enhance personalized treatment strategies for breast cancer patients.

Who should consider this trial

Good fit: Ideal candidates include female patients aged 18 and older with unilateral, invasive, hormone receptor-positive, HER2-negative breast cancer at clinical stage I or II.

Not a fit: Patients with HER2-positive breast cancer or those with advanced metastatic disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for patients with hormone receptor-positive breast cancer by identifying effective therapies based on individual tumor responses.

How similar studies have performed: Other studies have explored neoadjuvant endocrine therapy in breast cancer, but this specific approach focusing on molecular analyses for predicting resistance is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Unilateral diagnostic breast mammogram and ultrasound within 60 days of enrollment.
2. Pathologically proven diagnosis of invasive breast cancer, clinical stage I or II.
3. Patients must be clinically lymph node negative. Lymph node negativity must be confirmed by clinical exam and/or ultrasound imaging.
4. The patient must be female.
5. Age ≥18 years.
6. 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.
7. Human epidermal growth factor receptor 2 (HER2) /neu must be negative by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
8. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
9. Bilateral breast cancer and/or multifocal, multicentric disease is allowed.
10. 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.
11. The patient must qualify for endocrine treatment (treatment of choice), per the treating medical oncologist.
12. The patient must provide study-specific informed consent prior to study entry.
13. 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.
14. 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.
15. 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.).
16. Strong cytochrome P450 2D6 (CYP2D6) inhibitors will be prohibited with tamoxifen, as it can decrease the efficacy of tamoxifen. There are no known strong interactions with aromatase inhibitors.

Exclusion Criteria:

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

Where this trial is running

Milwaukee, Wisconsin

• Froedtert Hospital and the Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Lubna N Chaudhary, MD — Medical College of Wisconsin
• Study coordinator: Medical College of Wisconsin Cancer Center Clinical Trials Office

Conditions Breast Cancer; hormone receptor-positive; HER2-negative; endocrine therapy; neoadjuvant; anastrozole; letrozole; exemestane