RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes.

PURPOSE: This phase II trial is studying how well letrozole works in treating women with ductal carcinoma in situ.

Treatment with letrozole begins within 21 days of registration, and only after notification has been received from the UCSF Breast MRI Research Laboratory that the baseline MRI is acceptable. Protocol therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a MRI for disease evaluation at months 3 and 6. All patients will continue to take study drug until the day prior to surgery, whether at month 3 or at month 6 or may stop if they experience unacceptable toxicity. It is expected that decisions regarding any adjuvant treatment (eg, radiation and hormonal therapy) will be made individually based on the best practice guidelines, using informed and shared decision making between patient and provider. The primary and secondary objectives are provided below.

Primary objective:

1. To estimate the mean change in MRI tumor volume from pretreatment to completion of preoperative endocrine therapy in estrogen receptor-positive (ER+) ductal carcinoma in situ (DCIS), as well as to determine whether 3-month change in volume correlates with 6-month change.

Secondary objectives:

1. To assess radiographic-pathologic correlation between MRI findings and histopathology, including the prevalence of occult invasive cancer in patients undergoing neoadjuvant endocrine therapy for DCIS.
2. To compare changes in MRI maximum lesion diameter and mammographic extent at baseline and following treatment. These are two additional radiographic parameters which may also biological response to therapy.
3. To determine practice patterns of adjuvant hormonal and radiation therapy in patients who complete neoadjuvant letrozole therapy for DCIS.
4. To determine whether Ki67 is reduced with neoadjuvant letrozole treatment for DCIS, and to compare the reduction in proliferation between radiographic responders and non-responders.
5. To identify baseline IHC and expression biomarkers predictive of response to treatment, with response determined by extent of Ki67 reduction. Subsets showing the greatest reduction in Ki67 would be the most likely candidates for non-operative treatment in future studies.
6. To examine whether germline polymorphisms are associated with clinical endpoints, including treatment-related toxicity or efficacy outcomes, or with expression of biomarkers in serum or tumor.
7. To assess quality-of-life and musculoskeletal symptoms associated with neoadjuvant letrozole for ER positive DCIS.

Patients will be followed up to 6 months post-surgery.

Eligibility Criteria:

1. Histologic documentation: Pathologic confirmation of ductal carcinoma in situ (DCIS) of the female breast without invasive cancer, with diagnosis rendered on core biopsy only, completed within 60 days before registration. Patients diagnosed with DCIS on the basis of surgical biopsy are not eligible for this study.

   1. Patients with microinvasion on diagnostic core biopsy, defined as tumor ≤ 1 mm in greatest dimension, will be allowed to participate.
   2. All patients must have a clip placed, either at the time of the diagnostic biopsy or at the time of the baseline MRI prior to the start of treatment.

2. Tissue samples: Patient has diagnostic tissue available for correlative studies.

3. Clinical stage: Tis or T1mi N0, M0

4. Hormone receptor status: DCIS must express estrogen and/or progesterone receptor, as determined by immunohistochemical methods on the diagnostic pathology sample, according to the local institution's standard protocol. Greater than or equal to 1% cells will be considered to be positive.

5. Menopausal status: Patients must be postmenopausal defined as:

   1. Age ≥ 55 years and one year or more of amenorrhea
   2. Age < 55 years and one year or more amenorrhea, with an estradiol assay < 20pg/ml
   3. Surgical menopause with bilateral oophorectomy (at least 28 days must elapse from surgery to time of study registration)

   The use of GnRH analogs to achieve post menopausal status is not allowed.

6. Prior treatment:

   1. No prior surgical excision in the index breast for current DCIS diagnosis of DCIS
   2. Any exogenous hormone therapy must be completed 4 weeks prior to registration
   3. Any patients with a history of tamoxifen or raloxifene use within two years of current DCIS diagnosis are not eligible
   4. No prior neoadjuvant/adjuvant therapy for current DCIS diagnosis

7. Contraindication to MRI: No contraindications to breast MRI

8. Measurable disease: Mammographic extent of calcifications must be accurately measurable in at least one dimension with each lesion ≥ 1 cm and ≤ 7 cm

   1. DCIS must be visible on MRI based on central review.
   2. Patients with palpable DCIS or adenopathy are not eligible to participate.
   3. Patients with multifocal or bilateral disease are eligible.

9. History of osteoporosis: Women diagnosed with osteoporosis may participate in this trial provided they are receiving appropriate therapy or if they have declined therapy.

10. Age: Patients ≥ 18 years of age

11. Performance Status: ECOG performance status 0 or 1

12. Pregnancy/nursing status: Not pregnant or nursing

13. Required Initial Laboratory Values:

    1. ANC ≥ 1,000/μL
    2. Platelet count ≥ 100,000/μL
    3. Serum creatinine ≤ 1.7 mg/dL
    4. Bilirubin ≤ 2.0 mg/dL
    5. AST/ALT ≤ 2.5 times upper limit of normal
    6. Serum estradiol level assay < 20 pg/mL *Required for patients < 55 years of age and one year or more of amenorrhea