Gene Expression Following Short Term Exposure to Neoadjuvant Endocrine Therapy in Invasive Breast Cancer

Analysis of Gene Expression Following Short Term Exposure to Neoadjuvant Endocrine Therapy in Invasive Breast Cancer

The purpose of this pilot study is to see if taking anastrozole (Arimidex) for 10 days causes changes in breast cancer cells. Anastrozole (Arimidex) is a drug used in the treatment of a type of breast cancer that depends on estrogen to grow. This type of breast cancer is called estrogen receptor positive breast cancer. Anastrozole (Arimidex) works by blocking an enzyme in your body called aromatase. Aromatase is found in your muscles, fat, liver and in breast tumors. This enzyme is important for making estrogen in women who are no longer having menstrual periods. Anastrozole decreases levels of estrogen in the body. We are interested in seeing if taking anastrozole for 10 days will cause changes in breast cancer cells. We will study cell processes such as how they make new blood vessels, how quickly the cells multiply, and how soon they die. We will also study which genes in the breast cancer tissues are turned on or off by taking anastrozole for 10 days.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: anastrozole; Other: Placebo

Detailed Description

This is an exploratory study utilizing micro-array technology and immunohistochemistry to test the hypothesis that changes in gene expression occur as an early event in response to endocrine therapy and that these changes can be correlated with changes in surrogate biological markers.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal patients, defined as one or more of the following criteria:

Documented history of bilateral oophorectomy, Aged 60 years or more,

Aged 45-59 years and satisfying one or more of the following criteria:

Amenorrhea for at least 12 months and intact uterus Amenorrhea for less than 12 months and follicle stimulating hormone (FSH) concentrations within postmenopausal range including: patients who have had a hysterectomy and patients who have received hormone replacement therapy in the past.

• Clinically palpable or non-palpable T1c or greater, ER positive invasive breast cancer diagnosed by outside core biopsy.
• Outside diagnosis of invasive breast cancer confirmed at MSKCC
• Palpable or non-palpable breast mass > 1cm highly suspicious for invasive breast cancer based on mammographic, ultrasound and/or physical examination findings and amenable to diagnostic core biopsy.
• Core biopsy diagnosis of ER positive invasive breast cancer performed at MSKCC
• Breast conserving surgery or mastectomy scheduled at MSKCC.
• Informed consent obtained.

Exclusion Criteria:

• Co-morbid conditions which would preclude use of aromatase inhibitors such as: previous hypersensitivity, severe hepatic insufficiency (SGOT or SGPT three times the upper limit of normal), severe renal insufficiency (creatinine clearance <10ml/min).

Prior radiation therapy to chest wall / breast.

• Neoadjuvant chemotherapy
• Hormone replacement therapy, tamoxifen or raloxifene treatment within past 3 months
• ER negative breast cancer
• History of active malignancy within the previous 5 years (except for nonmelanoma skin cancer and breast cancer)

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; This is an exploratory study utilizing micro-array technology and immunohistochemistry to test the hypothesis that changes in gene expression occur as an early event in response to endocrine therapy and that these changes can be correlated with changes in surrogate biological markers.	Drug: anastrozole; anastrozole 1mg/day 11 days before their surgery and to take the last dose of the oral endocrine agent (anastrozole) on the day before their surgery.
Placebo Comparator: 2; no medication before surgery	Other: Placebo; No medication before surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine whether short term exposure to endocrine therapy (anastrozole) induces changes in gene expression in human invasive breast cancer.	conclusion of study

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the effects of anastrozole-mediated aromatase inhibition on surrogate biomarkers for cell proliferation, apoptosis, and angiogenesis.	conclusion of study

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Tari King, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan-Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: December 22, 2007
• First Submitted That Met QC Criteria: December 22, 2007
• First Posted (Estimate): January 8, 2008

Study Record Updates

• Last Update Posted (Estimate): December 24, 2015
• Last Update Submitted That Met QC Criteria: December 23, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Breast; ANASTROZOLE
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Anastrozole
• Other Study ID Numbers: 03-153