Low Dose Aspirin for the Prevention of Postpartum Related Breast Cancer

Targeted Prevention of Postpartum-Related Breast Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Carcinoma; Breast Fibrocystic Change; Benign Breast Neoplasm
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Biospecimen Collection; Drug: Low-Dose Aspirin; Procedure: Ultrasound-Guided Biopsy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic in Arizona
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Barbara A. Pockaj, M.D.
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Recruiting
      • Mayo Clinic in Florida
      • Principal Investigator: Sarah McLaughlin, M.D.
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Principal Investigator: Kathryn J. Ruddy, M.D.
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 planned mammoplasty or other breast surgery (e.g., breast reduction, breast implants, etc.) or willing to have research 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Prevention (low-dose aspirin); 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 by mouth daily for 42-65 days and undergo collection of blood on study. Patients may undergo ultrasound guided breast biopsy as clinically indicated.

Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo collection of blood; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Low-Dose Aspirin; Given PO; Other Names: Baby Aspirin; Procedure: Ultrasound-Guided Biopsy; Undergo ultrasound-guided breast biopsy; Other Names: Ultrasound Guided Biopsy; Ultrasound Biopsy

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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) lobules	Will be calculated based on 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
Change in serum C-reactive protein (CRP), estrogens, insulin/insulin-like growth factors (IGFs), and adipokines	Will be measured pre- and post-intervention for each person. Within person differences will be analyzed. The correlation between the change in PRBC score and change in the respective serum measures will be assessed using a Pearson correlation if both the values are normally distributed. If either value 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
Changes in tissue and urine prostaglandins (PGs) and PGE2	Will be measured pre- and post-intervention for each person. Within person differences will be analyzed. The correlation between the change in PRBC score and change in the respective PGs will be assessed using a Pearson correlation if both the values are normally distributed. If either value 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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Kathryn J. Ruddy, M.D., Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2023
• Primary Completion (Estimated): January 30, 2026
• Study Completion (Estimated): January 30, 2027

Study Registration Dates

• First Submitted: September 23, 2022
• First Submitted That Met QC Criteria: September 26, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Fibrocystic Breast Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: MC220301 (Other Identifier: Mayo Clinic); P30CA015083 (U.S. NIH Grant/Contract); NCI-2022-07430 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01CA262393 (U.S. NIH Grant/Contract); 22-000606 (Other Identifier: Mayo Cli)

Drug and device information, study documents

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