Clinical trial NCT00290745: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: breast cancer in situ
ductal breast carcinoma in situ
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2006-02-13
Enrollment: 79
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Median Change in 6-month Tumor Volume Compared to Baseline Using Mammography
timeFrame: Baseline and 6 months
measure: Median Change in 6-month Tumor Volume Compared to Baseline Using Magnetic Resonance Imaging (MRI)
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: Number of Responders to Neoadjuvant Therapy at Month 3
timeFrame: 3 months
measure: Number of Responders to Neoadjuvant Therapy at Month 6
timeFrame: 6 months
measure: Median Reduction in Tumor Volume by Estrogen Receptor Hormone (ER H-) Quartile Group
timeFrame: Baseline and 6 months
measure: Median Reduction in Tumor Volume by PgR H-score by Quartile Group
timeFrame: Baseline and 6 months
measure: Median Reduction in Tumor Volume by Ki-67 Average Score
timeFrame: Baseline and 6 months
measure: Correlation Between Pathologic Tumor Size at Radiographic (MRI) Tumor Size
timeFrame: 6 months
measure: Correlation Between Pathologic Tumor Size and Mammographic Tumor Size
timeFrame: 6 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: E. Shelley Hwang, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Frederic M. Waldman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Nola M. Hylton, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Rita Mukhtar, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.