Neratinib + Endocrine Therapy for Breast Cancer

The goal of this clinical trial is to learn if neratinib, an FDA-approved oral pan-HER2/3/4 inhibitor, improves disease control for participants with metastatic endocrine-resistant ER+/HER2-negative breast cancer. Neratinib is already approved for the treatment of HER2-postive breast cancers. The study will also learn about the safety of adding this drug to standard of care treatments. The main questions it aims to answer are:

1. Does adding neratinib to standard of care systemic therapy improve disease control for patients with metastatic hormone-driven breast cancer that is resistant to endocrine therapy?

2. What side effects do participants have when adding neratinib to standard of care therapy? Researchers will compare standard of care endocrine therapy regimens with and without neratinib to see if neratinib improves control of treatment-resistant metastatic breast cancer that has continued to progress while eon first line endocrine therapy.

Participants will:

1. Take standard of care endocrine therapy for metastatic endocrine-resistant breast cancer as determined by their medical oncologist or standard of care therapy with neratinib daily

2. Visit the clinic every 3 months for checkups, tests and imaging studies