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Tamoxifen or Letrozole in Treating Women With Ductal Carcinoma in Situ

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00290745
Recruitment Status : Completed
First Posted : February 13, 2006
Results First Posted : December 4, 2020
Last Update Posted : December 4, 2020
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Breast Cancer Drug: letrozole Drug: tamoxifen citrate Procedure: conventional surgery Procedure: neoadjuvant therapy Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 79 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Primary Hormonal Therapy for Ductal Carcinoma in Situ: Exploration of a Novel Approach to the Clinical Management of Noninvasive Breast Cancer
Actual Study Start Date : February 19, 2002
Actual Primary Completion Date : July 31, 2009
Actual Study Completion Date : June 30, 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: tamoxifen or letrozole
tamoxifen or letrozole work in treating women with ductal carcinoma in situ
Drug: letrozole
Drug: tamoxifen citrate
Procedure: conventional surgery
Procedure: neoadjuvant therapy



Primary Outcome Measures :
  1. Median Change in 6-month Tumor Volume Compared to Baseline Using Mammography [ Time Frame: 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

  2. Median Change in 6-month Tumor Volume Compared to Baseline Using Magnetic Resonance Imaging (MRI) [ Time Frame: 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 :
  1. Number of Responders to Neoadjuvant Therapy at Month 3 [ Time Frame: 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.

  2. Number of Responders to Neoadjuvant Therapy at Month 6 [ Time Frame: 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.

  3. Median Reduction in Tumor Volume by Estrogen Receptor Hormone (ER H-) Quartile Group [ Time Frame: 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.

  4. Median Reduction in Tumor Volume by PgR H-score by Quartile Group [ Time Frame: 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


  5. Median Reduction in Tumor Volume by Ki-67 Average Score [ Time Frame: 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

  6. Correlation Between Pathologic Tumor Size at Radiographic (MRI) Tumor Size [ Time Frame: 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.

  7. Correlation Between Pathologic Tumor Size and Mammographic Tumor Size [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00290745


Locations
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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Novartis
Investigators
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Principal Investigator: E. Shelley Hwang, MD, MPH University of California, San Francisco
Principal Investigator: Frederic M. Waldman, MD, PhD University of California, San Francisco
Principal Investigator: Nola M. Hylton, PhD University of California, San Francisco
Principal Investigator: Rita Mukhtar, MD University of California, San Francisco
Publications:
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.

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00290745    
Other Study ID Numbers: 017513
UCSF-H10367-19435-05 ( Other Identifier: University of California, San Francisco )
NCI-2011-01273 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
CDR0000465205 ( Other Identifier: University of California, San Francisco )
First Posted: February 13, 2006    Key Record Dates
Results First Posted: December 4, 2020
Last Update Posted: December 4, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by University of California, San Francisco:
breast cancer in situ
ductal breast carcinoma in situ
Additional relevant MeSH terms:
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Carcinoma
Breast Neoplasms
Carcinoma in Situ
Carcinoma, Ductal
Carcinoma, Intraductal, Noninfiltrating
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Breast Carcinoma In Situ
Tamoxifen
Letrozole
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents