Letrozole in Post-Menopausal Patients With Operable Hormone-Sensitive Breast Cancer

Inclusion Criteria

• Eligibility waivers are not permitted. Subjects must meet all of the inclusion and exclusion criteria to be registered to the study. Study treatment may not begin until a subject is registered.
• Patients must provide informed written consent
• ECOG performance status 0-2.
• Clinical stage operable I, II or III invasive mammary carcinoma, which is ER-positive by 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, mammogram 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 pg/mL (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.
• (There is no upper age limit for enrollment to this study)
• 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, USP, [Premarin]), at least 7 days prior to receiving the first dose of randomized therapy.
• Patients must have adequate hepatic and renal function. All tests must be obtained less than 4 weeks from study entry. This includes:
• Creatinine <2X upper limits of normal
• Bilirubin, SGOT, SGPT <1.5X upper limits of normal
• 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.