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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Tamoxifen Citrate
* Drug: Letrozole
* Drug: Exemestane
* Diagnostic Test: Blueprint
* Diagnostic Test: Mammaprint


Participation Criteria
=================
Eligibility Criteria
-----------------
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).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will start the hormone therapy before surgery; the investigators look for the genomic profiles of the tumor before and after chemotherapy
Masking: None (Open Label)


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
breast cancer, genomic assay, hormone therapy