To the best of our knowledge, our study is the first explorative analysis focused on the effects of a 12-week supervised PE protocol on cardiometabolic status, QoL, and PA in a population of BCS, not treated with anthracyclines or HER-2 inhibitors, providing data on BC and CV outcomes, PA, and QoL at a 34-month follow-up. The gene discussed is ERBB2; the disease is breast cancer.