The anthracycline doxorubicin, first introduced in the 1960's, continues to be an effectively utilized antineoplastic drug. Even at relatively low cumulative doses there is risk of cardiotoxicity. However, the incidence of subclinical cardiotoxicity is not known, carrying a potential risk for late effects in cancer survivors. Doxorubicin has systemic toxicity that may contribute to cardiac metabolic stress, but the main cardiotoxic mechanism involves cardiac mitochondria. The primary goal of this study is to detect early changes in the mitochondrial metabolism in situ as a marker for subclinical doxorubicin induced cardiotoxicity. The problem of cardiovascular complications following chemotherapy for breast cancer goes far beyond anthracyclines alone. In addition, other agents such as trastuzumab, and pertuzumab and emerging novel therapies may also promote cardiovascular injury. The secondary objective is to test the hypothesis that cardiotoxicity due to other medical anticancer therapies and radiation therapy involving the heart field is associated with a signature of early impaired aerobic cardiac metabolism through pyruvate dehydrogenase.

This is a prospective, single-center study in women and men with breast cancer requiring cardiotoxic therapy. The study will be conducted in parallel to the standard clinical care, at dedicated visits.

In this study patients will undergo a cardiac magnetic resonance (MR) signal detection after injection of hyperpolarized carbon-13 pyruvate. The study will be performed before the course of cardiotoxic therapy, and after completing the treatment.

Patients will be screened prior to enrollment based on study specific inclusion and exclusion criteria and MRI safety criteria.

On the day of the metabolic cardiac MR scan an IV line will be inserted and the participant will receive a bolus of oral glucose. The ingestion of glucose will be required to prepare the state of the heart for metabolic imaging. Following this preparation the participant will undergo a cardiac MR study of about 45 minutes, including carbon-13 dedicated sequences.

A separate dedicated cardiac MRI session may be completed in certain participants.

Feasibility Study (Part I) : Administration at two visits 1) after completion of cardiotoxic therapy and 2) 1 to 6 months after the first time point following medical therapy (SOC).

Formal Study (Part II) : Administration at two visits: 1) baseline MRI before administration of cardiotoxic therapy and 2) after completion of cardiotoxic therapy.

Inclusion Criteria:

• Female or male with breast cancer tissue diagnosis or a healthy volunteer.
• Plan for treatment as cardiotoxic therapy. Patients for the feasibility study must be post cardiotoxic therapy, and patients for the formal study should not have started the cardiotoxic therapy yet.
• Age ≥ 18 years
• Ability to understand and the willingness to sign a written informed consent
• While all races and ethnicities will be included, subjects must be able to read and speak the English language, and or, the Spanish Language.
• Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

A female of childbearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or

• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

  - Males must be surgically sterile or have a female partner using an acceptable method of contraception.

• Acceptable surgical sterilization techniques are vasectomy with surgery at least 6 months prior to dosing. Males must also refrain from sperm donation during the study and for 6 months following discontinuation of treatment.

• Acceptable methods of contraception for female partners of childbearing potential are an intrauterine device, contraceptive implant, and a barrier method (eg. Condom, diaphragm, cervical cap) during the study and for 6 months after patient discontinuation of treatment.

Exclusion Criteria:

• Patients for the feasibility study must be post cardiotoxic therapy

• Known Type 1 or Type 2 diabetes.

• Subjects who are receiving any other investigational agents that are not compatible with the study.

• Subjects with known remote, macro, metastases will be excluded from this clinical trial because of their poor prognosis.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Any contraindication per MRI Screening Form (Appendix A attached) including, but not limited to:

  • Metal Implants and devices contraindicated at 3T.
  • Breast tissue expanders.
  • Non-MR compatible IV port.
  • Claustrophobia.

• Female subjects who are already pregnant.

• Sickle cell disease

• Hemolytic anemia

• If the subject agrees to doing a cardiac function MRI scan with gadolinium based contrast agent intravenously:

eGFR ≤ 30 mL/min/1.73m2