Letrozole in Treating Postmenopausal Women With Ductal Carcinoma in Situ

• 3-month and 6-month radiographic tumor volume [ Designated as safety issue: No ]
  

• Radiographic response of MRI-measured tumor at 3 months and 6 months [ Designated as safety issue: No ]
  
• Radiographic response as measured by mammography at 3 months and 6 months [ Designated as safety issue: No ]
  
• Type of primary surgery (mastectomy or lumpectomy) [ Designated as safety issue: No ]
  
• Number of re-excisions required to obtain clear margins [ Designated as safety issue: No ]
  
• Extent of residual DCIS post surgery [ Designated as safety issue: No ]
  
• Presence of invasive cancer at surgery [ Designated as safety issue: No ]
  
• Size of margins (smallest) at surgery [ Designated as safety issue: No ]
  
• Treatment-related adverse events [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• 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

• 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.
• To compare changes in MRI maximum lesion diameter and mammographic extent at baseline and following treatment.
• To determine practice patterns of adjuvant hormonal and radiation therapy in patients who complete neoadjuvant letrozole therapy for DCIS.
• 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.
• To identify baseline IHC and expression biomarkers predictive of response to treatment, with response determined by extent of Ki67 reduction.
• 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.
• To assess quality-of-life and musculoskeletal symptoms associated with neoadjuvant letrozole for ER+ DCIS.

OUTLINE: This is a multicenter study.

Patients receive neoadjuvant letrozole orally (PO) once daily (QD) for 3 months. Patients then undergo MRI with an IV contrast. Patients with progressive disease discontinue letrozole and undergo surgery. Patients with complete, partial, or stable disease continue letrozole PO QD for an additional 3 months before undergoing another MRI and surgery. Patients continue receiving letrozole until the day before surgery.

Surgery (mastectomy or lumpectomy) must be performed within 30 days of the 3- or 6-month MRI.

Patients' core biopsy specimen and surgical excision specimen may be collected for correlative studies.

Patients may complete the Menopause Specific Quality-of-Life Questionnaire (MEMOQOL), the Brief Pain Inventory (BPI-SF), the Functional Assessment of Cancer Therapy - General (FACT-G), the Self-Efficacy for Coping with Side Effects, the Medication Taking Behavior (MMAS), and the Beliefs about Medicines Questionnaires at baseline and periodically during study.

After completion of study therapy, patients are followed up at 1, 3, and 6 months.