Back to resultsTamoxifen or Letrozole in Treating Women With Ductal Carcinoma in Situ
Primary Purpose
Breast Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
letrozole
tamoxifen citrate
conventional surgery
neoadjuvant therapy
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring breast cancer in situ, ductal breast carcinoma in situ
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of ductal carcinoma in situ (DCIS) on core biopsy No evidence of contralateral breast disease or palpable masses on breast examination No presence or suspicion of invasive cancer, including contralateral invasive cancer, on core biopsy and MRI No documented ipsilateral axillary adenopathy Planning to undergo lumpectomy or mastectomy Estrogen receptor (ER)-positive tumor by immunohistochemistry PATIENT CHARACTERISTICS: Female patient Premenopausal or postmenopausal Postmenopausal is defined by any of the following: No spontaneous menses for >= 1 year Bilateral oophorectomy Radiation castration and amenorrheic for >= 3 months Follicle-stimulating hormone (FSH) > 20 IU/L AND off all hormonal therapy (e.g., hormone replacement therapy or birth control pills) for >= 1 month Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No co-morbidities contraindicating the use of tamoxifen, including any of the following: Prior history of thrombotic events History of hypercoagulable state History of endometrial hyperplasia Abnormal vaginal bleeding No history of contrast dye-related allergies/reactions No history of metal-containing prostheses or implants PRIOR CONCURRENT THERAPY: See Disease Characteristics
Sites / Locations
- University of California, San Francisco
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
tamoxifen or letrozole
Arm Description
tamoxifen or letrozole work in treating women with ductal carcinoma in situ
Outcomes
Primary Outcome Measures
Median Change in 6-month Tumor Volume Compared to Baseline Using Mammography
Change in size of Ductal Carcinoma in situ (DCIS) for participants on hormonal therapy, as determined by mammography are determined by (1) largest diameter of tumor, as visualized on mammography (2) extent of disease on mammography (3) quantification of mammographically-detected change from baseline to 6-month and used to generate the change in tumor volume of mammographic extent of disease from baseline. Since values were not normally distributed, the median change was calculated, and Wilcoxon sign rank tests were used to evaluate the significance of these changes
Median Change in 6-month Tumor Volume Compared to Baseline Using Magnetic Resonance Imaging (MRI)
Change in size of Ductal Carcinoma in situ (DCIS) on hormonal therapy, as determined by MRI are determined by (1) largest diameter of tumor, as visualized on MRI (2) extent of disease on MRI (3) quantification of MR-detected change from baseline to 6-month and used to generate the change in tumor volume of MRI extent of disease from baseline. Since values were not normally distributed, the median change was calculated, and Wilcoxon sign rank tests were used to evaluate the significance of these changes.
Secondary Outcome Measures
Number of Responders to Neoadjuvant Therapy at Month 3
MRI volume response at each time point was classified as follows: 90% image-complete response (ICR90) is defined as a >90% reduction in tumor volume, 80% image-complete response (ICR80) is defined as an 81-90% reduction in tumor volume , partial response (PR) is defined as a 20-80% reduction in tumor volume, and sustained disease or progressive disease (SD/PD) defined as a <20% reduction or increase in volume.
Number of Responders to Neoadjuvant Therapy at Month 6
MRI volume response at each time point was classified as follows: 90% image-complete response (ICR90) is defined as a >90% reduction in tumor volume, 80% image-complete response (ICR80) is defined as an 81-90% reduction in tumor volume , partial response (PR) is defined as a 20-80% reduction in tumor volume, and sustained disease or progressive disease (SD/PD) defined as a <20% reduction or increase in volume.
Median Reduction in Tumor Volume by Estrogen Receptor Hormone (ER H-) Quartile Group
Tumor volume changes between baseline and surgery were calculated at month 6 and compared across baseline ER Hormone (H-) Score quartile. The ER H- scores are a percentage that tells you how many cells out of 100 stain positive for hormone receptors. Each participant is assigned an ER H- score at baseline with the full score range between 0 (none have receptors) and 100 (all have receptors). The participants were grouped into quartiles (four equal groups) based on their baseline ER H- score. ER H- score and the reduction in tumor volume from baseline to month 6 was measured for each quartile group.
Median Reduction in Tumor Volume by PgR H-score by Quartile Group
Tumor volume changes between baseline and surgery were calculated at month 6 and compared across baseline PgR Hormone (H-) Score quartile. The PgR H-scores are a percentage that tells you how many cells out of 100 stain positive for hormone receptors. Each participant is assigned a PgR H- score at baseline with the full PgR H score ranges between 0 (none have receptors) and 100 (all have receptors). The participants were grouped into quartiles (four equal groups) based on their baseline PgR H- score and the reduction in tumor volume from baseline to month 6 was measured for each quartile group.
A wilcoxon sign rank tests were used to evaluate the significance of these changes
Median Reduction in Tumor Volume by Ki-67 Average Score
Tumor volume changes between baseline and surgery were calculated at month 6 by Baseline Ki-67 Average Score which is divided into 2 groups: (1) <=10% or (2) >10% to 100%. In est results, the Ki-67 findings expressed as a percentage with less than 10% considered low Ki-67 expression and > than 10% or higher considered high. A "high" score means that the breast tumor is more likely to be aggressive and spread quickly. A wilcoxon sign rank tests were used to evaluate the significance of these changes
Correlation Between Pathologic Tumor Size at Radiographic (MRI) Tumor Size
Correlations between pathologic tumor size and maximum diameters of baseline and 6-month MRI extent of disease were evaluated using Spearman correlation coefficient measure of association. The Spearman's rank-order correlation (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.
Correlation Between Pathologic Tumor Size and Mammographic Tumor Size
Correlations between pathologic tumor size and maximum diameters of baseline and pre-surgical mammographic extent of disease were evaluated using Spearman correlation coefficient measure of association. The Spearman's rank-order correlation (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.
Full Information
NCT ID
NCT00290745
First Posted
February 9, 2006
Last Updated
November 10, 2020
Sponsor
University of California, San Francisco
Collaborators
Novartis
1. Study Identification
Unique Protocol Identification Number
NCT00290745
Brief Title
Tamoxifen or Letrozole in Treating Women With Ductal Carcinoma in Situ
Official Title
Primary Hormonal Therapy for Ductal Carcinoma in Situ: Exploration of a Novel Approach to the Clinical Management of Noninvasive Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
February 19, 2002 (Actual)
Primary Completion Date
July 31, 2009 (Actual)
Study Completion Date
June 30, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Novartis
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen or 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 clinical trial is studying how well tamoxifen or letrozole work in treating women with ductal carcinoma in situ.
Detailed Description
OBJECTIVES:
Determine the clinical response in women with estrogen receptor-positive ductal carcinoma in situ (DCIS) treated with neoadjuvant hormonal therapy comprising tamoxifen or letrozole, by evaluating the maximal change in tumor diameter on mammography and MRI following treatment.
Identify those cellular antigens which are altered by hormonal therapy.
Determine which cellular antigens are predictive of clinical response to hormonal therapy.
Evaluate whether genomic changes or gene expression in DCIS are altered by hormonal therapy and find candidate genes which are correlated with response to treatment.
OUTLINE: This is a pilot study.
Patients who are premenopausal receive oral tamoxifen once daily for 3 months in the absence of unacceptable toxicity. Patients who are post menopausal receive oral letrozole once daily for 3 months in the absence of unacceptable toxicity.
After 3 months of hormonal therapy, patients undergo lumpectomy or mastectomy.
After completion of study treatment, patients are followed every 6 months for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
breast cancer in situ, ductal breast carcinoma in situ
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
79 (Actual)
8. Arms, Groups, and Interventions
Arm Title
tamoxifen or letrozole
Arm Type
Experimental
Arm Description
tamoxifen or letrozole work in treating women with ductal carcinoma in situ
Intervention Type
Drug
Intervention Name(s)
letrozole
Intervention Type
Drug
Intervention Name(s)
tamoxifen citrate
Intervention Type
Procedure
Intervention Name(s)
conventional surgery
Intervention Type
Procedure
Intervention Name(s)
neoadjuvant therapy
Primary Outcome Measure Information:
Title
Median Change in 6-month Tumor Volume Compared to Baseline Using Mammography
Description
Change in size of Ductal Carcinoma in situ (DCIS) for participants on hormonal therapy, as determined by mammography are determined by (1) largest diameter of tumor, as visualized on mammography (2) extent of disease on mammography (3) quantification of mammographically-detected change from baseline to 6-month and used to generate the change in tumor volume of mammographic extent of disease from baseline. Since values were not normally distributed, the median change was calculated, and Wilcoxon sign rank tests were used to evaluate the significance of these changes
Time Frame
Baseline and 6 months
Title
Median Change in 6-month Tumor Volume Compared to Baseline Using Magnetic Resonance Imaging (MRI)
Description
Change in size of Ductal Carcinoma in situ (DCIS) on hormonal therapy, as determined by MRI are determined by (1) largest diameter of tumor, as visualized on MRI (2) extent of disease on MRI (3) quantification of MR-detected change from baseline to 6-month and used to generate the change in tumor volume of MRI extent of disease from baseline. Since values were not normally distributed, the median change was calculated, and Wilcoxon sign rank tests were used to evaluate the significance of these changes.
Time Frame
Baseline and 6 months
Secondary Outcome Measure Information:
Title
Number of Responders to Neoadjuvant Therapy at Month 3
Description
MRI volume response at each time point was classified as follows: 90% image-complete response (ICR90) is defined as a >90% reduction in tumor volume, 80% image-complete response (ICR80) is defined as an 81-90% reduction in tumor volume , partial response (PR) is defined as a 20-80% reduction in tumor volume, and sustained disease or progressive disease (SD/PD) defined as a <20% reduction or increase in volume.
Time Frame
3 months
Title
Number of Responders to Neoadjuvant Therapy at Month 6
Description
MRI volume response at each time point was classified as follows: 90% image-complete response (ICR90) is defined as a >90% reduction in tumor volume, 80% image-complete response (ICR80) is defined as an 81-90% reduction in tumor volume , partial response (PR) is defined as a 20-80% reduction in tumor volume, and sustained disease or progressive disease (SD/PD) defined as a <20% reduction or increase in volume.
Time Frame
6 months
Title
Median Reduction in Tumor Volume by Estrogen Receptor Hormone (ER H-) Quartile Group
Description
Tumor volume changes between baseline and surgery were calculated at month 6 and compared across baseline ER Hormone (H-) Score quartile. The ER H- scores are a percentage that tells you how many cells out of 100 stain positive for hormone receptors. Each participant is assigned an ER H- score at baseline with the full score range between 0 (none have receptors) and 100 (all have receptors). The participants were grouped into quartiles (four equal groups) based on their baseline ER H- score. ER H- score and the reduction in tumor volume from baseline to month 6 was measured for each quartile group.
Time Frame
Baseline and 6 months
Title
Median Reduction in Tumor Volume by PgR H-score by Quartile Group
Description
Tumor volume changes between baseline and surgery were calculated at month 6 and compared across baseline PgR Hormone (H-) Score quartile. The PgR H-scores are a percentage that tells you how many cells out of 100 stain positive for hormone receptors. Each participant is assigned a PgR H- score at baseline with the full PgR H score ranges between 0 (none have receptors) and 100 (all have receptors). The participants were grouped into quartiles (four equal groups) based on their baseline PgR H- score and the reduction in tumor volume from baseline to month 6 was measured for each quartile group.
A wilcoxon sign rank tests were used to evaluate the significance of these changes
Time Frame
Baseline and 6 months
Title
Median Reduction in Tumor Volume by Ki-67 Average Score
Description
Tumor volume changes between baseline and surgery were calculated at month 6 by Baseline Ki-67 Average Score which is divided into 2 groups: (1) <=10% or (2) >10% to 100%. In est results, the Ki-67 findings expressed as a percentage with less than 10% considered low Ki-67 expression and > than 10% or higher considered high. A "high" score means that the breast tumor is more likely to be aggressive and spread quickly. A wilcoxon sign rank tests were used to evaluate the significance of these changes
Time Frame
Baseline and 6 months
Title
Correlation Between Pathologic Tumor Size at Radiographic (MRI) Tumor Size
Description
Correlations between pathologic tumor size and maximum diameters of baseline and 6-month MRI extent of disease were evaluated using Spearman correlation coefficient measure of association. The Spearman's rank-order correlation (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.
Time Frame
6 months
Title
Correlation Between Pathologic Tumor Size and Mammographic Tumor Size
Description
Correlations between pathologic tumor size and maximum diameters of baseline and pre-surgical mammographic extent of disease were evaluated using Spearman correlation coefficient measure of association. The Spearman's rank-order correlation (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.
Time Frame
6 months
10. Eligibility
Sex
Female
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS:
Diagnosis of ductal carcinoma in situ (DCIS) on core biopsy
No evidence of contralateral breast disease or palpable masses on breast examination
No presence or suspicion of invasive cancer, including contralateral invasive cancer, on core biopsy and MRI
No documented ipsilateral axillary adenopathy
Planning to undergo lumpectomy or mastectomy
Estrogen receptor (ER)-positive tumor by immunohistochemistry
PATIENT CHARACTERISTICS:
Female patient
Premenopausal or postmenopausal
Postmenopausal is defined by any of the following:
No spontaneous menses for >= 1 year
Bilateral oophorectomy
Radiation castration and amenorrheic for >= 3 months
Follicle-stimulating hormone (FSH) > 20 IU/L AND off all hormonal therapy (e.g., hormone replacement therapy or birth control pills) for >= 1 month
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No co-morbidities contraindicating the use of tamoxifen, including any of the following:
Prior history of thrombotic events
History of hypercoagulable state
History of endometrial hyperplasia
Abnormal vaginal bleeding
No history of contrast dye-related allergies/reactions
No history of metal-containing prostheses or implants
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
E. Shelley Hwang, MD, MPH
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Frederic M. Waldman, MD, PhD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nola M. Hylton, PhD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rita Mukhtar, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
19689789
Citation
Chen YY, DeVries S, Anderson J, Lessing J, Swain R, Chin K, Shim V, Esserman LJ, Waldman FM, Hwang ES. Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ. BMC Cancer. 2009 Aug 18;9:285. doi: 10.1186/1471-2407-9-285.
Results Reference
background
Citation
Swain RS, Chen YY, Wa C, et al.: Pathologic and biologic response to neoadjuvant anti-estrogen (AE) therapy in patients with ductal carcinoma in situ (DCIS). [Abstract] United States and Canadian Academy of Pathology 95th Annual Meeting, February 11-17, 2006, Atlanta, GA. A-186, 2006.
Results Reference
background
Learn more about this trial
Tamoxifen or Letrozole in Treating Women With Ductal Carcinoma in Situ
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