Chemoprevention Trial - Anastrozole in Ductal Carcinoma In Situ (DCIS) in Postmenopausal Women

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Chao Family Comprehensive Cancer Center, University of California, Irvine
ClinicalTrials.gov Identifier:
NCT00256217
First received: November 16, 2005
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

Breast cancer is one of the most common cancers seriously afflicting women in the United States. Of the one million incident cases that are reported annually there are approximately 193,000 new cases of breast cancer (Greenlee, 2001). Although significant advances have been made both in early detection and treatment of breast cancer, the impact of these on reduction in mortality has been modest (Peta, 2000). Furthermore, despite data implicating diet and other environmental risk factors, no lifestyle changes have yet been shown to significantly reduce the risk of breast cancer. Therefore, chemoprevention of breast cancer is a worthwhile approach to reduce the incidence of breast cancer.

There is every reason to believe that a detailed understanding of the initiation, promotion and growth of breast cancer will ultimately provide a rational strategy upon which to base prevention strategies. While the pathways of breast cancer development are not yet fully understood, a role for estrogens in breast cancer etiology has been well established.

While many pathways are involved in breast cancer etiology, including loss of tumor suppressor function by p53 or BRCA1 and gain of HER2 oncogene expression, their exact role in an individual patient's cancer development may vary.

Therefore, it may be advantageous to focus on a chemoprevention strategy that may have a more uniform impact on breast cancer development, such as estrogen exposure. Estrogen and its metabolites, both in the circulation and locally synthesized in the breast, are important in the pathogenesis of breast cancer. High levels of circulating estrogen in postmenopausal women have been associated with an increased risk of breast cancer (Clemons, 2001). Furthermore, local estrogen synthesis, i.e. aromatase activity, in the breast may also be important in the development of breast cancer.


Condition Intervention Phase
DCIS
Drug: Anastrozole
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Chemoprevention Trial - Anastrozole in the DCIS and Early Invasive Breast Cancer in Postmenopausal Women

Resource links provided by NLM:


Further study details as provided by University of California, Irvine:

Primary Outcome Measures:
  • To assess the efficacy in terms of reduction in Ki-67 [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To measure the histopathological response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To compare pretreatment vascular density with post treatment vascular density using MRI [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To compare pretreatment markers of angiogenesis with post treatment marker of angiogenesis [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: September 2004
Estimated Study Completion Date: December 2018
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anastrozole Drug: Anastrozole
1 mg. oral every day for 2 - 4 weeks
Other Name: ARIMIDEX

Detailed Description:

Specific Aim 1: We hypothesize that a proliferative marker Ki-67 is reduced in patients with preinvasive Ductal Carcinoma In Situ (DCIS) and very early breast cancer treated with anastrozole. To establish reduction in Ki-67 as a primary surrogate endpoint to breast cancer risk reduction in patients treated with anastrozole we will measure Ki-67 before and after treatment with anastrozole. Consistent with this, it has been demonstrated by Geisler et al that patients with advanced breast cancer show a decrease in Ki-67 on lumpectomy/mastectomy samples when anastrozole is administered for few weeks prior to definitive surgery. In addition, there is a trend for a more profound suppression in those achieving an objective response. Ki-67 will be measured by routine immunohistochemistry.

Specific Aim 2: We hypothesize that histopathological tumor response will be demonstrated in 30-40 percent of patients with preinvasive (DCIS) and early invasive (less than 2 cm) breast cancer treated with anastrozole. The percent ability to reverse early breast cancer lesions in patients treated with anastrozole will be qualified as a secondary surrogate endpoint to breast cancer risk reduction. Consistent with this, it has been demonstrated that 30-40 percent of patients with advanced breast cancer show an infiltration of foamy macrophages and fibrosis on lumpectomy/mastectomy samples when chemotherapy is administered for few months prior to definitive surgery. Further, there is a trend for a more profound change in those achieving a complete clinical response. Importantly, a complete pathological response in these advanced breast cancer has been shown to correlate with improved disease free survival and overall survival in breast cancer patients. A corollary is that if reversibility of early carcinogenic lesions is reliably demonstrated in our present proposal, it would translate into chemoprevention of breast cancer.

Specific Aim 3: To compare the pretreatment MRI with post treatment MRI (as a secondary surrogate endpoint to breast cancer risk reduction). We hypothesize that tumor response can be measured by contrast washout characteristic in patients with preinvasive and very early breast cancer treated with aromatase inhibitor. Consistent with this, we have previously demonstrated that patients with advanced breast cancer show a reduction in vascularity in response to chemotherapy. Further, there is a trend for a more profound suppression in those achieving a pathological response on lumpectomy/mastectomy specimen.

Specific Aim 4: To compare the pretreatment markers of angiogenesis with post treatment markers of angiogenesis (as a secondary surrogate endpoint to breast cancer risk reduction). We hypothesize that tumor response can be measured by reduction in CD31 (microvessel count), CD105 (endoglin) and VEGF in response to hormonal therapy. There may be upregulation of TSP-1, an angiogenesis inhibitor in response to anastrozole. Angiogenic activity has been reported for ligands of the nuclear hormone receptor superfamily such as estrogens. Inhibition of the proangiogenic effects of estrogens could underlie the chemopreventive action of hormone modulators on mammary carcinogenesis. A group of investigators have indeed coined the word angioprevention as a mechanism of chemoprevention that reverses the angiogenic switch from preinvasive to invasive cancer. Additionally, it has been demonstrated that patients with various cancers whose tumor vascularity is targeted with VEGF inhibitor show higher response than patients who are treated with chemotherapy alone. Our present proposal capitalizes on the data obtained in advanced breast cancer as to the efficacy of antiangiogenesis mechanism as an option in treatment and prevention .

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have suspicion of DCIS or early invasive breast cancer on mammography.
  • Patients must have histologically confirmed diagnosis of DCIS or early invasive breast cancer on core biopsy for final registration.
  • Patients must be over 18 years of age
  • "Patients must be postmenopausal as defined by one of the following criteria:

    1. Prior bilateral oophorectomy OR
    2. > 12 months since LMP with no prior hysterectomy OR
    3. a & b not applicable AND age >=50
  • Patients must be positive for either ER or PR or both
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

  • Patients must not have diagnosis of osteoporosis (T-score -2.5 according to the WHO)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00256217

Locations
United States, California
Chao Family Comprehensive Cancer Center
Orange, California, United States, 92868
Sponsors and Collaborators
University of California, Irvine
AstraZeneca
Investigators
Principal Investigator: Rita Mehta, MD Chao Family Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Chao Family Comprehensive Cancer Center, Cancer Center, University of California, Irvine
ClinicalTrials.gov Identifier: NCT00256217     History of Changes
Other Study ID Numbers: UCI 03-16, 2004-3681, NCI-2010-00361
Study First Received: November 16, 2005
Last Updated: January 30, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Anastrozole
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014