The Effects of Short-term Preoperative Treatment With Hormonal Therapy on Gene Profiles in Breast Cancer

The investigators would like to study the genetic and molecular outcomes that results after a short term neoadjuvant hormonal therapy on patients with breast cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tamoxifen Citrate; Diagnostic test: Blueprint; Diagnostic test: Mammaprint; Drug: Letrozole; Drug: Exemestane

Detailed Description

Breast cancer is among the most common malignancies in women in the United States. Over the years breast cancer management have dramatically developed from the extensive surgical approach toward the breast conservative approach. This was mainly due to the introduction of chemotherapy and hormonal therapy. Hormonal therapy in particular has been shown to improve the oncological outcomes of the breast cancer. However, while this is well documented in the clinical outcomes. Little is known in regards what happens on the genetic level. As such in this study the investigators would like to study the genetic and molecular outcomes that results after a short term neoadjuvant hormonal therapy on patients with breast cancer.

The hypothesis of this study is that short-term, preoperative hormonal treatment will induce genetic changes associated with reduced proliferation, including lower Ki67 expression, and changes in Estrogen Receptor (ER) and Progesterone Receptor (PR) expression. The data from such investigation will be very helpful in advancing the individualized care to women with breast cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• Treatment-naïve, histologically confirmed invasive ductal breast cancer between stages 1 to 3.
• Co-enrollment in the FLEX Registry
• Estrogen Receptor Positive (ER+) Progesterone Receptor Positive (PR+) confirmed hormone receptor status measured by immunohistochemistry (IHC)
• Patients should understand patients' condition and be able to give informed consent to participate

Exclusion criteria

• History of hormonal therapy, chemotherapy, radiation therapy, or novel therapy to treat the current breast cancer.
• Allergic reactions/hypersensitivity to tamoxifen, letrozole, or exemestane or any of the ingredients of these drugs.
• Any contraindication to hormonal therapy, such as history of thromboembolic disease or uterine cancer.
• Patients without invasive disease (stage 0)
• Patients with metastatic breast cancer(stageIV)
• Patients that are Human Epidermal Growth Factor 2+(HER2+) by IHC/Fluorescence in situ hybridization (FISH).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tamoxifen arm; for premenopausal patients	Drug: Tamoxifen Citrate; 10mg administered daily. Patients take this drug for 2-6 weeks; Other Names: Soltamox; Diagnostic test: Blueprint; studies the genomics of the tumor and tumor behavior; Diagnostic test: Mammaprint; studies the genomics of the tumor
Experimental: Letrozole arm; for postmenopausal patients	Diagnostic test: Blueprint; studies the genomics of the tumor and tumor behavior; Diagnostic test: Mammaprint; studies the genomics of the tumor; Drug: Letrozole; 2.5mg is administered daily. Patients take this drug for 2-6 weeks; Other Names: Femara
Experimental: Exemestane arm; for postmenopausal patients	Diagnostic test: Blueprint; studies the genomics of the tumor and tumor behavior; Diagnostic test: Mammaprint; studies the genomics of the tumor; Drug: Exemestane; 25mg is administered daily. Patients take this drug for 2-6 weeks.; Other Names: Aromasin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in percent expression of Ki67 measured by immunohistochemistry (IHC)	This is a measure of tumor proliferation, and will be determined at baseline and at time of surgery.	Baseline and at Time of surgery, up to 6 weeks
Change in percent expression of Ki67 measured by single-gene read out	This is a measure of tumor proliferation, and will be determined at baseline and at time of surgery.	Baseline and at Time of surgery, up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Mammaprint risk report	Mammaprint risk score is binary (high risk of recurrence or low risk of recurrence).	Baseline and at Time of surgery, up to 6 weeks
Change in percent ER expression as measured by IHC	Units for Estrogen Receptor protein expression are percent based. >10 percent is positive, <1 percent is negative. 1-10 percent is weakly positive or focally positive.	Baseline and at Time of surgery, up to 6 weeks
Change in percent ER expression as measured by single-gene read out	Units for Estrogen Receptor protein expression are percent based. >10 percent is positive, <1 percent is negative. 1-10 percent is weakly positive or focally positive.	Baseline and at Time of surgery, up to 6 weeks
Change in percent PR expression as measured by IHC	Units for Progesterone Receptor protein expression are percent based. >10 percent is positive, <1 percent is negative. 1-10 percent is weakly positive or focally positive.	Baseline and at Time of surgery, up to 6 weeks
Change in percent PR expression as measured by single-gene read out	Units for Progesterone Receptor protein expression are percent based. >10 percent is positive, <1 percent is negative. 1-10 percent is weakly positive or focally positive.	Baseline and at Time of surgery, up to 6 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Agendia
• Investigators: Principal Investigator: Mehran Habibi, MD, Johns Hopkins Bayview

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2019
• Primary Completion (Actual): November 10, 2022
• Study Completion (Anticipated): November 26, 2023

Study Registration Dates

• First Submitted: May 17, 2019
• First Submitted That Met QC Criteria: October 15, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 11, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: breast cancer; hormone therapy; genomic assay
• 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; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Tamoxifen; Exemestane
• Other Study ID Numbers: IRB00130428

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No