Breast Carcinoma
Conditions
Keywords
Invasive breast carcinoma, breast carcinoma stage T1cN0 to N3N0
Brief summary
The overall purpose of this study is to assess whether celecoxib can reduce the change in collagen alignment and inflammatory response in the tumor tissue of primary breast cancer patients with invasive breast carcinoma after 2 weeks of oral intake.
Detailed description
Advances in early detection techniques and improvement in systemic treatment of early stage breast cancer have led to a small decline in overall breast cancer mortality in the last 20 years. New advances will require understanding of breast cancer biology at the molecular level. Inhibition of COX-2 and its analysis of effect in breast cancer tumor microenvironment provide one such fruitful therapeutic target. Tumor microenvironment is poorly understood in breast cancer research. Despite new drugs being developed to treat breast cancer and tested in clinical trials, it is rarely possible to assess how the drug is affecting the breast cancer cells at a molecular level. The use of collagen properties such as alignment and deposition will allow giving a faster diagnosis of breast cancer status and seeing how celecoxib with respect to collagen can change the tumor microenvironment in human tissue. This window trial provides a way to look at cancer and stromal cells before and after celecoxib intake to see if the drug is actively working. If we can do this before and after a patient has surgery, and see how the tumor microenvironment responds, then the physician could pick a better suited adjuvant treatment for this patient after surgical intervention that would improve their overall survival rate.
Interventions
DRUGCelecoxib
Celecoxib is the only COX-2 inhibitor currently approved by the FDA to be used in the United States. Recently, it has been shown that celecoxib prevents sporadic colorectal adenomas and there are more clinical trials evaluating the use of celecoxib in combination with chemotherapy regimens in breast cancer settings. Celebrex® oral capsules that will be used in this study contain 200 mg of celecoxib, in combination with inactive ingredients that include the following components: croscarmellose sodium, edible inks, gelatin, lactose monohydrate, magnesium stearate, povidone and sodium lauryl sulfate.
Sponsors
National Cancer Institute (NCI)
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
Due to the characteristics of the design of this clinical trial, the patient will not be blinded but the researcher completing analysis will be. The researcher will be handling deidentified patient samples and comparing whether there are changes of biological markers within the same patient before and after celecoxib intake. It is important that the researcher be as unbiased as possible when analyzing collagen alignment and amount of other breast cancer biological markers.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participants must have biopsy proven invasive breast carcinoma stages T1cN0 to T3N0, ER or PR positive with tumors greater than 1cm without lymph node spread. * Participants must have a mammographic breast composition category (density) of c or d. * Participants must be willing to participate and provide signed informed consent. * Participants must have no immediate requirements for chemotherapy, radiotherapy or hormonal therapy. * Participants must be willing to discontinue any use of NSAIDs like aspirin or ibuprofen until the tumor is removed * Participants cannot be taking the following medications because of major pharmacokinetic interactions with celecoxib while being enrolled in the study: Abciximab, Argatroban, Bivalirudin, Cilostazol, Dabigatran, Etexilate, Dipyridamole, Fondaparinux, Heparin, Lepirudin, Pemetrexed, Protein C, Rivaroxaban, Sibutramine, Ticlopidine, Tirofiban, Vilazodone and Warfarin. * Participants should pass MRI screening questionnaire
Exclusion criteria
* Prior history of cancer, neo-adjuvant chemotherapy and radiation therapy * No daily NSAIDs intake within the past 4 weeks. Intermittent non-daily NSAIDs is allowed under PI discretion. * Current or prior systemic use of corticosteroids in the past month. * Participants with history of hypertension, congestive heart failure, edema, stroke or other cardiac disease or condition. * Participants with type 2 diabetes, documented stomach ulcers and pulmonary embolism. * Participants with aspirin or other NSAIDs-induced asthma or hypersensitivity reaction, sulfonamide allergy * Participants who are currently pregnant * Participants with known human immunodeficiency virus (HIV) infection, hepatitis B carrier state or with clinical evidence of hepatitis B. * Participants who are not able to understand or provide written informed consent. * Participants with standard contraindications to non-contrast MRI will be excluded, including claustrophobia and metallic implants incompatible with MRI. * Participants whose girth exceeds the bore of the MRI scanner. * Participants requiring conscious sedation for MR imaging.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in collagen | Up to 6 weeks | To determine change of collagen structure and proliferation in response to celecoxib intake in the tumor microenvironment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Syndecan-1 | Up to 6 weeks | To analyze Syndecan-1 expression levels as stromal response biomarkers. |
| Changes in CD68 | Up to 6 weeks | To analyze CD68 expression levels as stromal response biomarkers. |
| Changes in CD163 | Up to 6 weeks | To analyze CD163 expression levels as stromal response biomarkers. |
| Changes in neutrophil elastase | Up to 6 weeks | To analyze neutrophil elastase expression levels as stromal response biomarkers. |
| Changes in vimentin | Up to 6 weeks | To analyze vimentin expression levels as stromal response biomarkers. |
| Change in correlation of collagen alignment and COX-2 expression | Up to 6 weeks | To evaluate correlation among collagen alignment and COX-2 expression before and after celecoxib intake. |
| Changes in Ki67 | Up to 6 weeks | To analyze Ki67 expression levels as stromal response biomarkers. |
| Changes in tissue cytokines in dense breast tissue | Up to 6 weeks | To discover tissue cytokines present in dense breast tissue that are altered in response to celecoxib. |
| Number of subjects with adverse events associated with celecoxib | Up to 6 weeks | To evaluate any adverse events associated with the 2-week intake of 200mg celecoxib twice a day. |
| Changes in collagen due to relationship of amount/percentage of fibroglandular tissue | Up to 6 weeks | To determine if changes in collagen structure and proliferation in response to celecoxib differ by the amount and/or percentage of fibroglandular tissue, measured quantitatively using MRI. |
| Changes in α-SMA | Up to 6 weeks | To analyze α-SMA expression levels as stromal response biomarkers. |
Outcome results
None listed