Breast Cancer
Conditions
Keywords
breast cancer, genomic assay, hormone therapy
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.
Interventions
DRUGTamoxifen Citrate
10mg administered daily. Patients take this drug for 2-6 weeks
DRUGLetrozole
2.5mg is administered daily. Patients take this drug for 2-6 weeks
DRUGExemestane
25mg is administered daily. Patients take this drug for 2-6 weeks.
DIAGNOSTIC_TESTBlueprint
studies the genomics of the tumor and tumor behavior
DIAGNOSTIC_TESTMammaprint
studies the genomics of the tumor
Sponsors
Agendia
Johns Hopkins University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Patients will start the hormone therapy before surgery; the investigators look for the genomic profiles of the tumor before and after chemotherapy
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percent Expression of Ki67 Measured by Immunohistochemistry (IHC) | Baseline and at Time of surgery up to 6 weeks after the start of hormone therapy | This is a measure of tumor proliferation, and will be determined at baseline and at time of surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Low or High Score in MammaPrint | Baseline and at Time of surgery (up to 6 weeks) | Mammaprint risk score is binary (high risk of recurrence or low risk of recurrence). |
| Median Percent of Tissue ER Positive | Baseline and at Time of surgery (up to 6 weeks) | Median percent of tissue ER positive in matched tissue measured by Immunohistochemistry (IHC) |
| Median Percent of Tissue PR Positive | Baseline and at Time of surgery (up to 6 weeks) | Median percent of tissue PR positive in matched tissue measured by Immunohistochemistry (IHC) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tamoxifen Arm for premenopausal patients
Tamoxifen Citrate: 10mg administered daily. Patients take this drug for 2-6 weeks
Blueprint: studies the genomics of the tumor and tumor behavior
Mammaprint: studies the genomics of the tumor | 10 |
| Letrozole Arm for postmenopausal patients
Letrozole: 2.5mg is administered daily. Patients take this drug for 2-6 weeks
Blueprint: studies the genomics of the tumor and tumor behavior
Mammaprint: studies the genomics of the tumor | 10 |
| Exemestane Arm for postmenopausal patients
Exemestane: 25mg is administered daily. Patients take this drug for 2-6 weeks.
Blueprint: studies the genomics of the tumor and tumor behavior
Mammaprint: studies the genomics of the tumor | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | Total | Tamoxifen Arm | Letrozole Arm | Exemestane Arm |
|---|---|---|---|---|
| Age, Customized 55 and above | 23 participants | 3 participants | 10 participants | 10 participants |
| Age, Customized below 55 | 7 participants | 7 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized African American | 15 participants | 4 participants | 5 participants | 6 participants |
| Race/Ethnicity, Customized Caucasian | 15 participants | 6 participants | 5 participants | 4 participants |
| Sex: Female, Male Female | 29 Participants | 9 Participants | 10 Participants | 10 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
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.
Time frame: Baseline and at Time of surgery up to 6 weeks after the start of hormone therapy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen Arm | Change in Percent Expression of Ki67 Measured by Immunohistochemistry (IHC) | -3.6 Change in percentage expression of ki 67 | Standard Deviation 1.06 |
| Letrozole Arm | Change in Percent Expression of Ki67 Measured by Immunohistochemistry (IHC) | -5.1 Change in percentage expression of ki 67 | Standard Deviation 1.82 |
| Exemestane Arm | Change in Percent Expression of Ki67 Measured by Immunohistochemistry (IHC) | -4.2 Change in percentage expression of ki 67 | Standard Deviation 1.71 |
Secondary
Median Percent of Tissue ER Positive
Median percent of tissue ER positive in matched tissue measured by Immunohistochemistry (IHC)
Time frame: Baseline and at Time of surgery (up to 6 weeks)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tamoxifen Arm | Median Percent of Tissue ER Positive | Time of surgery (up to 6 weeks) median percent of tissue ER positive | 95 percent of tissue ER positive |
| Tamoxifen Arm | Median Percent of Tissue ER Positive | Baseline median percent of tissue ER positive | 98 percent of tissue ER positive |
| Letrozole Arm | Median Percent of Tissue ER Positive | Time of surgery (up to 6 weeks) median percent of tissue ER positive | 95 percent of tissue ER positive |
| Letrozole Arm | Median Percent of Tissue ER Positive | Baseline median percent of tissue ER positive | 93 percent of tissue ER positive |
| Exemestane Arm | Median Percent of Tissue ER Positive | Time of surgery (up to 6 weeks) median percent of tissue ER positive | 95 percent of tissue ER positive |
| Exemestane Arm | Median Percent of Tissue ER Positive | Baseline median percent of tissue ER positive | 95 percent of tissue ER positive |
Secondary
Median Percent of Tissue PR Positive
Median percent of tissue PR positive in matched tissue measured by Immunohistochemistry (IHC)
Time frame: Baseline and at Time of surgery (up to 6 weeks)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tamoxifen Arm | Median Percent of Tissue PR Positive | Baseline median percent of tissue PR positive | 97 percent of tissue PR positive |
| Tamoxifen Arm | Median Percent of Tissue PR Positive | Time of surgery (up to 6 weeks) median percent of tissue PR positive | 90 percent of tissue PR positive |
| Letrozole Arm | Median Percent of Tissue PR Positive | Baseline median percent of tissue PR positive | 33 percent of tissue PR positive |
| Letrozole Arm | Median Percent of Tissue PR Positive | Time of surgery (up to 6 weeks) median percent of tissue PR positive | 0 percent of tissue PR positive |
| Exemestane Arm | Median Percent of Tissue PR Positive | Baseline median percent of tissue PR positive | 83 percent of tissue PR positive |
| Exemestane Arm | Median Percent of Tissue PR Positive | Time of surgery (up to 6 weeks) median percent of tissue PR positive | 7 percent of tissue PR positive |
Secondary
Number of Participants With Low or High Score in MammaPrint
Mammaprint risk score is binary (high risk of recurrence or low risk of recurrence).
Time frame: Baseline and at Time of surgery (up to 6 weeks)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tamoxifen Arm | Number of Participants With Low or High Score in MammaPrint | low risk mammaprint score at baseline | 5 Participants |
| Tamoxifen Arm | Number of Participants With Low or High Score in MammaPrint | high risk mammaprint score at baseline | 5 Participants |
| Tamoxifen Arm | Number of Participants With Low or High Score in MammaPrint | low risk mammaprint score at time of surgery (up to 6 weeks) | 7 Participants |
| Tamoxifen Arm | Number of Participants With Low or High Score in MammaPrint | high risk mammaprint score at time of surgery (up to 6 weeks) | 3 Participants |
| Letrozole Arm | Number of Participants With Low or High Score in MammaPrint | high risk mammaprint score at time of surgery (up to 6 weeks) | 2 Participants |
| Letrozole Arm | Number of Participants With Low or High Score in MammaPrint | low risk mammaprint score at baseline | 7 Participants |
| Letrozole Arm | Number of Participants With Low or High Score in MammaPrint | low risk mammaprint score at time of surgery (up to 6 weeks) | 8 Participants |
| Letrozole Arm | Number of Participants With Low or High Score in MammaPrint | high risk mammaprint score at baseline | 3 Participants |
| Exemestane Arm | Number of Participants With Low or High Score in MammaPrint | high risk mammaprint score at time of surgery (up to 6 weeks) | 3 Participants |
| Exemestane Arm | Number of Participants With Low or High Score in MammaPrint | high risk mammaprint score at baseline | 5 Participants |
| Exemestane Arm | Number of Participants With Low or High Score in MammaPrint | low risk mammaprint score at time of surgery (up to 6 weeks) | 7 Participants |
| Exemestane Arm | Number of Participants With Low or High Score in MammaPrint | low risk mammaprint score at baseline | 5 Participants |