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Phase II Chemoprevention Trial - Anastrozole in the DCIS and Early Invasive Breast Cancer in Postmenopausal Women


Phase 2
18 Years
N/A
Not Enrolling
Female
DCIS

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Trial Information

Phase II Chemoprevention Trial - Anastrozole in the DCIS and Early Invasive Breast Cancer in Postmenopausal Women


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 .


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)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To assess the efficacy in terms of reduction in Ki-67

Outcome Time Frame:

3 years

Safety Issue:

No

Principal Investigator

Rita Mehta, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Chao Family Comprehensive Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

UCI 03-16

NCT ID:

NCT00256217

Start Date:

September 2004

Completion Date:

January 2013

Related Keywords:

  • DCIS
  • Carcinoma in Situ
  • Carcinoma, Intraductal, Noninfiltrating

Name

Location

Chao Family Comprehensive Cancer CenterOrange, California  92868