Low Dose Aspirin for the Prevention of Postpartum Related Breast Cancer

Study Overview
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Brief Summary
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This phase II trial tests whether low-dose aspirin can affect markers of inflammation in postpartum (after childbirth) patients with benign breast disease planning to have a breast biopsy. Chronic inflammation may increase the risk of postpartum related breast cancer. Low-dose aspirin is a non-steroidal anti-inflammatory drug. Giving low-dose aspirin may affect markers of inflammation in blood and tissue and may prevent postpartum related breast cancer.

Detailed Description
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PRIMARY OBJECTIVE: I. Pre- versus (vs) post-intervention change in postpartum-related breast cancer (PRBC) score. SECONDARY OBJECTIVE: I. Pre- vs. post-intervention change in postpartum involution (PPI) signature score. EXPLORATORY OBJECTIVES: I. Pre- vs. post-intervention change in percent of epithelial cells positive for COX-2, estrogen receptor (ER)/Ki67, gammaH2AX, and p16 in normal and in benign breast disease (BBD) lobule. II. Pre- vs. post-intervention change in serum C-reactive protein (CRP), estrogens, insulin/insulin-like growth factors (IGFs), and adipokines. III. Pre- vs. post-intervention changes in tissue and urine prostaglandins (PGs) and PGE2. OUTLINE: Patients undergo standard of care breast biopsy for assessment of abnormalities seen on imaging, as well as collection of blood during screening. If cancer is found, patient is taken off study and treatment options are discussed with treating physician. Patients without a cancer finding on biopsy then receive low-dose aspirin orally (PO) daily and undergo collection of blood on study. Patients may undergo ultrasound guided breast biopsy as clinically indicated.

Official Title
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Targeted Prevention of Postpartum-Related Breast Cancer

Conditions
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Benign Breast Neoplasm, Breast Carcinoma, Breast Fibrocystic Change

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Drug: Low-Dose Aspirin
* Other: Questionnaire Administration
* Procedure: Ultrasound-Guided Biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PRE-REGISTRATION: Age >= 18 years and =< 45 years of age PRE-REGISTRATION: Presence of lesion suspicious for benign breast disease and planned breast biopsy or Breast biopsy =< 12 months prior to pre-registration for benign breast disease with tissue available for research. PRE-REGISTRATION: Had a live birth =< 10 years prior to pre-registration PRE-REGISTRATION: Pre-menopausal according to patient report and/or clinical determination PRE-REGISTRATION: Provide written informed consent PRE-REGISTRATION: Ability to complete questionnaire(s) by themselves or with assistance PRE-REGISTRATION: Willingness to provide mandatory blood and urine specimens for correlative research PRE-REGISTRATION: Willingness to provide mandatory tissue specimens for correlative research REGISTRATION: Age >= 18 years and =< 45 years of age REGISTRATION: Histological confirmation of benign breast disease (i.e., no evidence of DCIS or invasive cancer) REGISTRATION: Registration for this study must be completed either =< one (1) year after the qualifying pre-registration biopsy performed for this study or =< one (1) year after collection of the archived tissue (for those who did not have a pre-registration biopsy performed after pre-registration for this study) REGISTRATION: Hemoglobin >= 9.0 g/dL (obtained =< 30 days prior to registration) REGISTRATION: Platelet count >= 100,000/mm^3 (obtained =< 30 days prior to registration REGISTRATION: Serum creatinine =< 2.0 mg/dl (obtained =< days prior to registration) REGISTRATION: Negative pregnancy test done =< 14 days prior to registration REGISTRATION: Willing to use contraception while on treatment REGISTRATION: Provide written informed consent REGISTRATION: Ability to complete questionnaire(s) by themselves or with assistance REGISTRATION: Willingness to provide mandatory blood and urine specimens for correlative research REGISTRATION: Willingness to provide mandatory tissue specimens for correlative research REGISTRATION: Willing to return to enrolling institution for follow-up REGISTRATION: Known or suspected active breast infection Exclusion Criteria: PRE-REGISTRATION: History of breast cancer including ductal breast carcinoma in situ (DCIS) PRE-REGISTRATION: Received systemic treatment for any other cancer at any time PRE-REGISTRATION: Currently taking aspirin or other non-steroidal anti-inflammatory drugs (NSAIDS) (no doses within =< 5 days prior to pre-registration and no more than eight doses within =< 30 days prior to pre-registration) PRE-REGISTRATION: Currently taking other agents for the prevention of breast cancer PRE-REGISTRATION: Currently taking anticoagulants PRE-REGISTRATION: Contraindication for aspirin use PRE-REGISTRATION: Known or suspected active breast infection REGISTRATION: No research tissue available from pre-registration biopsy or from archived tissue (collected =< 12 months prior to pre-registration) REGISTRATION: Currently taking aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) (NOTE: no doses within =< 5 days prior to registration and no more than four doses within =< 30 days prior to registration) REGISTRATION: Co-morbid illnesses/conditions which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens REGISTRATION: Any contraindication to aspirin use including but not limited to: Bleeding disorders (e.g., hemophilia) Stomach or intestinal bleeding =< 6 months prior to registration Known allergy to other non-steroidal anti-inflammatory drugs (NSAIDs) REGISTRATION: Currently taking anticoagulants REGISTRATION: Any prior or current malignancy requiring prior or current systemic therapy REGISTRATION: Currently pregnant or planning to become pregnant in the next 90 days REGISTRATION: Post-menopausal: Prior bilateral surgical oophorectomy or No menses for > 1 year with estradiol levels within postmenopausal range, according to institutional standard Known or suspected active breast infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prevention (low-dose aspirin)<br>Patients undergo standard of care breast biopsy for assessment of abnormalities seen on imaging, as well as collection of blood during screening. If cancer is found, patient is taken off study and treatment options are discussed with treating physician. Patients without a cancer finding on biopsy then receive low-dose aspirin PO daily and undergo collection of blood on study. Patients may undergo ultrasound guided breast biopsy as clinically indicated. | Procedure: Biospecimen Collection<br>* Undergo collection of blood<br>* Other names: Specimen Collection;Drug: Low-Dose Aspirin<br>* Given PO<br>* Other names: Baby Aspirin;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Ultrasound-Guided Biopsy<br>* Undergo ultrasound-guided breast biopsy<br>* Other names: Ultrasound Guided Biopsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pregnancy-related breast cancer (PRBC) score | Will transform the biomarkers using Van der Waerden rank transformations. Will analyze data as within person differences for pre- versus post-treatment PRBC scores in tissues. The final mean difference in PRBC score point estimate and corresponding 95% confidence interval will be reported. | Pre- versus (vs) post-intervention up to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in postpartum involution (PPI) signature score | Will be calculated pre- and post-intervention for each person. Within person differences will be analyzed. The correlation between the change in PRBC score and change in PPI signature will be assessed using a Pearson correlation if both the scores are normally distributed. If either score is non-normally distributed, a Spearman correlation will be used instead. The correlation coefficient point estimate and 95% confidence interval will be reported. | Pre- vs. post-intervention up to 30 days |