Understanding Heart Risks of People With HER2-Positive Breast Cancer That Has Spread

Inclusion Criteria

• STEP 1 REGISTRATION
• Patients must have metastatic breast cancer and be initiating within 11 calendar days of step 1 registration or be continuing trastuzumab–based HER-2 targeted therapy without concurrent anthracyclines and be receiving the trastuzumab-based HER-2 targeted therapy for metastatic disease in first, second, third, or fourth line setting. Patients may have brain metastasis. There is no limit for number of doses of HER-2 targeted therapy prior to registration. Examples of eligible HER-2 targeted therapy: * Trastuzumab or a trastuzumab biosimilar * Trastuzumab + chemotherapy or hormonal therapy * Trastuzumab + other HER-2 targeted agent with or without chemotherapy (such as pertuzumab, lapatinib, and tucatinib) * Ado-trastuzumab (Kadcyla [registered trademark]) * Fam-trastuzumab deruxtecan (Enhertu) ** NOTE: Patients on lapatinib without trastuzumab are not eligible; planned treatment with concurrent HER-2 targeted therapy and anthracyclines is not permitted
• Patients must be at increased risk for cardiotoxicity defined by at least one of the following: * Previous anthracycline exposure, OR * 1 or more of the following risk factors for heart disease: ** Left ventricular ejection fraction (LVEF) 50-54% by local echocardiography (ECHO) read ** Age >= 65 ** Body mass index (BMI) >= 30 kg/m^2 ** Current or prior anti-hypertensive therapy ** Diagnosis of coronary artery disease (CAD) ** Diagnosis of diabetes mellitus ** Diagnosis of atrial fibrillation/flutter *** ECHO can be performed at any time prior to registration with the most recent being sent
• Patients must not have taken within 21 days prior to step 1 registration, be currently taking at the time of step 1 registration, or planning to take once registered to step 1 a beta blocker, ARB, or ACE inhibitor in order to be randomized (Arms 1 and 2) * Patients enrolling in the observational cohort (Arm 3) must be currently taking a beta blocker, ARB, or ACE inhibitor at the time of step 1 registration ** NOTE: Arm 3 was permanently closed to accrual between Revision #5 and Revision #7. Arms 1 and 2 have been permanently closed to accrual and Arm 3 has been reopened effective with the distribution of Revision #7. Participants enrolled prior to the closure of arms 1 and 2 remain eligible and should continue study participation.
• Patients must have a Zubrod performance status of 0-2
• Patients must be at >= 18 years of age
• Patients must have a complete physical examination and medical history within 28 days prior to registration
• Patients must have LVEF >= 50% by echocardiogram (2-dimensional [D] or 3D) within 28 days prior to registration. The echocardiogram must be obtained from the site's approved S1501 Validated ECHO laboratory (Lab) and submitted for central review by the S1501 ECHO Core Lab * If a 3D echocardiogram is performed at baseline, sites must ensure that standard 2D images, including 4-chamber and 2-chamber views, are also obtained and submitted at subsequent timepoints ** Note: For sites performing a 3D scan at baseline, please see the Coverage Analysis Worksheet on Cancer Trials Support Unit (CTSU) for additional coverage considerations * All follow-up echocardiograms (every 12 weeks) must be performed using 2D imaging to allow for standardized assessments. Follow-up scans must be completed at a site that can provide 2D images per protocol requirements. The echocardiograms cannot be submitted for central read until after Step 1 registration is complete
• Serum bilirubin < 3.0 x institutional upper limit of normal (IULN) (within 28 days prior to registration)
• Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) < 5.0 x IULN (within 28 days prior to registration)
• Patients must not be dialysis dependent
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer on active surveillance, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
• Patients must not be pregnant or nursing due to potential fetal or nursing infant harm. Women/men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
• NOTE: Arms 1 and 2 have been permanently closed to accrual and Arm 3 has been reopened effective with the distribution of Revision #7. The above criteria apply to participants enrolled on Arms 1 and 2 effective with the distribution of Revision #7
• Patients must be willing to submit blood specimens
• Sites must seek additional patient consent for the future use of specimens
• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
• STEP 2 REGISTRATION (Randomization)
• Patients must not be registered to step 2 until confirming via RAVE electronic data capture (EDC) that the patient’s LVEF by echocardiogram was >= 50% by central review; patients must be registered within 11 calendar days of submission of the ECHO study
• Site must verify that there is no known change in the step 1 eligibility since initial registration