Inclusion Criteria:

* STEP 1 REGISTRATION
* Patients must have metastatic breast cancer and be initiating within 7 days of step 1 registration or continuing trastuzumab?based HER-2 targeted therapy without concurrent anthracyclines in first or second 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
* Trastuzumab + chemotherapy or hormonal therapy
* Trastuzumab + other HER-2 targeted agent with or without chemotherapy (such as pertuzumab)
* Ado-trastuzumab (Kadcyla)
* 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)
* Diabetes mellitus
* Atrial fibrillation/flutter
* 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 currently taking a beta blocker, ARB, or ACE inhibitor at the time of step 1 registration are eligible to register for the non-randomized observational cohort (Arm 3)
* Patients must not be currently taking or planning to take during study treatment the following medications:

* B2 agonists
* Bosutinib
* Ceritinib
* Floctafenine
* Methacholine
* Pazopanib
* Rivastigmine
* Vincristine
* Silodosin
* Patients must have a Zubrod Performance status of 0-2
* Patients must have a complete physical examination and medical history within 28 days prior to registration
* Patients must have LVEF \>= 50% by 2-dimensional (D) echocardiogram within 28 days prior to registration; the echocardiogram must be obtained from a S1501 validated ECHO laboratory (lab) and submitted for central review by the S1501 ECHO core lab; ECHO should not be submitted for central read until patient has been otherwise deemed eligible
* Serum bilirubin \< 3.0 x institutional upper limit of normal (IULN)
* Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) \< 5.0 x IULN
* Patients must have electrocardiogram with corrected QT (QTc) with correction within 28 days prior to registration
* Patients must have a systolic blood pressure \>= 80 mm Hg within 14 days prior to registration
* Patients must not be dialysis dependent
* Patients must be able to swallow tablets
* Patients must not have uncontrolled asthma
* Patients must not co-enroll on other treatment trials
* 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
* 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
* As a part of the 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 receiving confirmation from the ECHO Core Lab that the patient?s LVEF by echocardiogram was \>= 50% by central review; patients must be registered within 5 calendar days of receiving the e-mail notification
* Site must verify that there is no known change in the step 1 eligibility since initial registration