Genetic Testing in Studying Letrozole Resistance in Post-Menopausal Patients with ER-positive or Her2-negative Operable Stages I-III Breast Cancer Pre-Surgery

Inclusion Criteria

• Patients must provide informed written consent
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Clinical stage operable I, II or III invasive mammary carcinoma, which is ER-positive by immunohistochemistry (IHC) and HER2-negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per routine clinical testing * Patients who have measurable residual tumor at the primary site * Patients who will undergo surgical treatment with either segmental resection or total mastectomy
• Measurable tumor *Measurable disease: a mass that can be reproducibly measured by physical exam and calipers or ultrasound and is at least 1 cm in size
• Post-menopausal female subjects >= 18 years of age, as defined by any of the following: * Subjects at least 55 years of age; ** Subjects under 55 years of age and amenorrhoeic for at least 12 months or follicle-stimulating hormone (FSH) values >= 40 IU/L and estradiol levels =< 40 IU/L (140 pmol/L) or in postmenopausal ranges per local or institutional reference ranges ** Prior bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months
• No prior chemotherapy for this primary breast cancer
• Patients with a prior history of contralateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer
• Women may have been taking tamoxifen or raloxifene as a preventive agent prior to study entry but must have discontinued the drug for at least 14 days prior to study enrollment
• Subjects must have ended hormone replacement therapy (HRT) (e.g., conjugated estrogens tablets, United States Pharmacopeia [USP], [Premarin]), at least 7 days prior to receiving the first dose of randomized therapy
• Creatinine =< 2 x upper limits of normal (obtained less than 4 weeks from study entry)
• Bilirubin =< 1.5 x upper limits of normal (obtained less than 4 weeks from study entry)
• Serum glutamic-oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) =< 1.5 x upper limits of normal (obtained less than 4 weeks from study entry)
• Able to swallow and retain oral medication

Exclusion Criteria

• Patients with locally advanced disease who are candidates for other preoperative chemotherapy at the time of initial evaluation. This may include patients with locally advanced disease such as: * Inflammatory breast cancer (T4d) * Fixed axillary lymph node metastases (N2) * Metastasis to ipsilateral internal mammary node (N3)
• Locally recurrent breast cancer
• Evidence of distant metastatic disease (i.e. lung, liver, bone, brain, etc.)
• Serious medical illness that in the judgment of the treating physician places the patient at high risk of operative mortality
• Severe uncontrolled malabsorption condition or disease (i.e. grade II/III diarrhea, severe malnutrition, short gut syndrome)
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
• Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of letrozole