Ignite Creation Date:
2024-05-05 @ 12:09 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00256217
Status:
COMPLETED
Last Update Posted:
2021-05-11
First Post:
2005-11-16
Brief Title:
Chemoprevention Trial - Anastrozole in Ductal Carcinoma In Situ DCIS in Postmenopausal Women
Sponsor:
Rita Sanghvi Mehta
Organization:
University of California Irvine
Study Overview
Official Title:
Phase II Chemoprevention Trial - Anastrozole in the DCIS and Early Invasive Breast Cancer in Postmenopausal Women
Status:
COMPLETED
Status Verified Date:
2021-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 193000 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 patients 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 ie aromatase activity in the breast may also be important in the development 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 patients 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 ie aromatase activity in the breast may also be important in the development of breast cancer
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 lumpectomymastectomy 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 lumpectomymastectomy 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 lumpectomymastectomy 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
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 lumpectomymastectomy 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 lumpectomymastectomy 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2010-00361 | OTHER | NCI Clinical Trials Reporting Program CTRP | None |
| 2004-3681 | OTHER | None | None |