Letrozole in Treating Postmenopausal Women With Ductal Carcinoma in Situ
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.
Procedure: conventional surgery
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Neoadjuvant Letrozole for Postmenopausal Women With Estrogen Receptor Positive Ductal Carcinoma In SITU (DCIS)|
- 3-month and 6-month radiographic tumor volume [ Time Frame: 3-months and 6-months ] [ Designated as safety issue: No ]
- Radiographic response of MRI-measured tumor at 3 months and 6 months [ Time Frame: 3-months and 6-months ] [ Designated as safety issue: No ]
- Radiographic response as measured by mammography at 3 months and 6 months [ Time Frame: 3-months and 6-months ] [ Designated as safety issue: No ]
- Type of primary surgery (mastectomy or lumpectomy) [ Time Frame: 3-months and 6-months ] [ Designated as safety issue: No ]
- Number of re-excisions required to obtain clear margins [ Time Frame: 3-months and 6-months ] [ Designated as safety issue: No ]
- Extent of residual DCIS post surgery [ Time Frame: Up to 6 months post-surgery ] [ Designated as safety issue: No ]
- Presence of invasive cancer at surgery [ Time Frame: 3-months and 6-months ] [ Designated as safety issue: No ]
- Size of margins (smallest) at surgery [ Time Frame: 3-months and 6-months ] [ Designated as safety issue: No ]
- Treatment-related adverse events [ Time Frame: Up to 6 months post surgery ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2012|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
Experimental: letrozole + MRI + surgery
Patients receive letrozole (2.5 mg) one tablet each day after confirmation that the MRI is acceptable. There is a 3 and 6 month disease evaluation by MRI of both breasts. If the DCIS has grown, the patient will have surgery to remove it and will continue to take letrozole until the day before surgery. It is expected that decisions regarding any adjuvant treatment will be made individually based on best practice guidelines, using informed and shared decision making between the patient and provider.
|Drug: letrozole Procedure: MRI Procedure: conventional surgery|
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.
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.
- 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. These are two additional radiographic parameters which may also biological response to therapy.
- 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. Subsets showing the greatest reduction in Ki67 would be the most likely candidates for non-operative treatment in future studies.
- 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 positive DCIS.
Patients will be followed up to 6 months post-surgery.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01439711
|Contact: Shelley Hwang, MD, PhD||919-684-6849|
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|Study Chair:||Shelley Hwang, MD, MPH||Duke University|