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:

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 beconfirmed 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 stainingcells by immunohistochemistry, according to the current American Society of ClinicalOncology/College of American Pathologists guidelines.

7. Human epidermal growth factor receptor 2 (HER2) /neu must be negative byimmunohistochemistry (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 clinicalevidence for distant metastases, based upon the following minimum diagnostic workup:history/physical examination, including breast exam (inspection and palpation of thebreasts), clinically negative axillary lymph nodes, within 28 days prior to studyentry.

11. The patient must qualify for endocrine treatment (treatment of choice), per thetreating 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 theyhave completed all treatment (including endocrine therapy) more than two years priorto registration.

14. Patients must not have had a prior treatment for this breast cancer or for anymalignancy diagnosed or treated within the past two years, with the exception ofnon-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 methodsand/or non-hormonal methods (Intrauterine devices etc.).

16. Strong cytochrome P450 2D6 (CYP2D6) inhibitors will be prohibited with tamoxifen, asit can decrease the efficacy of tamoxifen. There are no known strong interactionswith 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 carcinomain situ).

4. Men with breast cancer. Male breast cancer is a rare event and it is unclear ifneoadjuvant endocrine treatment approach is safe in men.

5. Medical, psychiatric or other condition that would prevent the patient fromreceiving the protocol therapy or providing informed consent.

6. Pregnant or lactating women are ineligible.