Tamoxifen or Letrozole in Treating Women With Ductal Carcinoma in Situ

Phase 1

Completed

Conditions: Breast Cancer

Interventions: Drug: letrozole
Drug: tamoxifen citrate
Procedure: conventional surgery
Procedure: neoadjuvant therapy

Registration Number: NCT00290745

Lead Sponsor: University of California, San Francisco

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 79

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
tamoxifen or letrozole	conventional surgery	tamoxifen or letrozole work in treating women with ductal carcinoma in situ
tamoxifen or letrozole	neoadjuvant therapy	tamoxifen or letrozole work in treating women with ductal carcinoma in situ
tamoxifen or letrozole	letrozole	tamoxifen or letrozole work in treating women with ductal carcinoma in situ
tamoxifen or letrozole	tamoxifen citrate	tamoxifen or letrozole work in treating women with ductal carcinoma in situ

Primary Outcome Measures

Name	Time	Method
Median Change in 6-month Tumor Volume Compared to Baseline Using Mammography	Baseline and 6 months	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)	Baseline and 6 months	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

Name	Time	Method
Number of Responders to Neoadjuvant Therapy at Month 3	3 months	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	6 months	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	Baseline and 6 months	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	Baseline and 6 months	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	Baseline and 6 months	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	6 months	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	6 months	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.