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

Inclusion criteria

• 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.

Exclusion criteria

• 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.