Saying goodbye to primary endocrine resistance for advanced breast cancer?

Cyclin-dependent 4/6 is a vital resistance pathway as it has a targetable treatment. According to the European Society for Medical Oncology (ESMO) guidelines, as an expert opinion, primary endocrine resistance is defined as relapse while on the first 2 years of adjuvant endocrine treatment (ET), or progressive disease (PD) within first 6 months of first-line ET for advanced breast cancer (ABC), while on ET. This definition is based on endocrine monotherapy used in the adjuvant and metastatic process. It is obvious that the concept of primary endocrine resistance defined by ESMO for adjuvant is still applicable. However, the concept of primary endocrine resistance defined for metastatic disease is no longer viable. We think that a new concept such as "primary ET + CDK 4/6 resistance" should be defined. Because the progression-free survival achieved with monotherapies in metastatic disease does not exceed 12 months, this period has reached 27 months with ET + CDK 4/6 inhibitors. We think that the 6 months defined for primary endocrine resistance in patients with ABC during endocrine monotherapy is too short for patients receiving ET + CDK 4/6 inhibitor. Therefore, the concept of novel primary ET + CDK 4/6 inhibitor resistance should be created to be used in patients with ABC. The concept of ET + CDK 4/6 inhibitor resistance to be defined may be used in the stratification of clinical trials aimed at determining subsequent treatments in patients who progressed under ET + CDK 4/6 inhibitor.