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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexFemale
• Healthy volunteersNo

You may be able to join 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.).
• 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.

You cannot join 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.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

letrozole. A nonsteroidal inhibitor of estrogen synthesis with antineoplastic activity. As a third-generation aromatase inhibitor, letrozole selectively and reversibly inhibits aromatase, which may result in growth inhibition of estrogen-dependent breast cancer cells. Aromatase, a cytochrome P-450 enzyme localized to the endoplasmic reticulum of the cell and found in many tissues including those of the premenopausal ovary, liver, and breast, catalyzes the aromatization of androstenedione and testosterone into estrone and estradiol, the final step in estrogen biosynthesis. NCI Drug Dictionary

tamoxifen citrate. The citrate salt of an antineoplastic nonsteroidal selective estrogen receptor modulator (SERM). Tamoxifen competitively inhibits the binding of estradiol to estrogen receptors, thereby preventing the receptor from binding to the estrogen-response element on DNA. The result is a reduction in DNA synthesis and cellular response to estrogen. In addition, tamoxifen up-regulates the production of transforming growth factor B (TGFb), a factor that inhibits tumor cell growth, and down-regulates insulin-like growth factor 1 (IGF-1), a factor that stimulates breast cancer cell growth. Tamoxifen also down-regulates protein kinase C (PKC) expression in a dose-dependant manner, inhibiting signal transduction and producing an antiproliferative effect in tumors such as malignant glioma and other cancers that overexpress PKC. NCI Drug Dictionary

Treatments listed in the registry

• 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.

Na · Single Group · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• surgery: Part of the study plan

Main goals

• Change from baseline in the number of subjects with increased HER-1 receptor tyrosine kinases protein expression in tumors. (Time of surgery)
• Change from baseline in the number of subjects with increased HER-2 receptor tyrosine kinases protein expression in tumors. (Time of surgery)
• Change from baseline in the number of subjects with increased HER-3 receptor tyrosine kinases protein expression in tumors. (Time of surgery)
• Change from baseline in the number of subjects with increased HER-4 receptor tyrosine kinases protein expression in tumors. (Time of surgery)

Planned enrollment: 185 (estimated).

• Froedtert Hospital and the Medical College of Wisconsin, Milwaukee, Wisconsin

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT06361940
• NCI Drug Dictionary: C1527
• NCI Drug Dictionary: C855

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 19, 2026. Public record; not medical advice.