Tamoxifen or Letrozole in Treating Women With Ductal Carcinoma in Situ

Breast Cancer Clinical Trial

Official title:

Primary Hormonal Therapy for Ductal Carcinoma in Situ: Exploration of a Novel Approach to the Clinical Management of Noninvasive Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00290745
• Other study ID #: 017513
• Secondary ID: UCSF-H10367-1943
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 19, 2002
• Est. completion date: June 30, 2011

Study information

• Verified date: November 2020
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: June 30, 2011
• Est. primary completion date: July 31, 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Carcinoma
• Carcinoma in Situ
• Carcinoma, Ductal
• Carcinoma, Intraductal, Noninfiltrating

Intervention

Drug:
• letrozole

• tamoxifen citrate

Procedure:
• conventional surgery

• neoadjuvant therapy

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Novartis

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Baseline and 6 months
Primary	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.	Baseline and 6 months
Secondary	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.	3 months
Secondary	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.	6 months
Secondary	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.	Baseline and 6 months
Secondary	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	Baseline and 6 months
Secondary	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	Baseline and 6 months
Secondary	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.	6 months
Secondary	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.	6 months