Thus, in addition to biomarker selection strategies such as PAM50, more complete coverage of HR-HER2 crosstalk and associated downstream signaling (in this case, by the addition of CDK4/6 inhibition) may offer future clinical consideration of chemotherapy-free regimens as neoadjuvant treatment for HR+/HER2+ early breast cancer. The gene discussed is CDK4; the disease is breast carcinoma.