ENERGIZE: Engagement With a Nurturing Exercise Routine for Greater Improvement in Zest and Energy on Enhertu: A Single-Center Pilot Study

Inclusion Criteria: * Subject aged ≥ 18 years * Diagnosis of locally advanced/unresectable or metastatic breast cancer. Note: Patients with High-Risk HER-2 + breast cancer after completion of neoadjuvant chemotherapy requiring adjuvant Enhertu are allowed at the discretion of the treating physician. * Has received 3 or 4 cycles of Enhertu and is expected to continue treatment for at least 12 weeks. Note: HER-2 targeted systemic therapy (e.g. Trastuzumab and/or Pertuzumab) in conjunction with Enhertu is allowed. * Able and willing to participate in the interventional aerobic exercise and resistance exercises. * Currently following standard of care contraception requirements and willing to continue following these requirements for the duration of therapy. * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. * Experiencing clinical fatigue symptoms in the opinion of the investigator. * Subject has completed the ACSM exercise preparticipation health screening and is, in the opinion of the investigator, fit to participate in this study. Exclusion Criteria: -Currently adhering to national physical activity guidelines for resistance training, as defined as participating in structured resistance training ≥ two days per week. * Structured is defined as time set aside in the subject's day to workout. * Resistance training is defined as exercises which use weights, bands, or body weight (e.g., squats or push-ups). AND Currently participating in structured moderate-intensity aerobic exercise for ≥ 150 minutes per week. * Moderate-intensity exercise is defined as activities where the subject can talk but not sing. * Aerobic exercise includes, but is not limited to, walking, swimming, cycling, running, rowing, hiking, and elliptical. * Medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol or complete the study. * Participants taking prohibited medications as described in Section 6.4.1.