Neuroendocrine differentiation in metastatic breast cancer following CDK 4/6 inhibitors.

Abstract

e13029 Background: First-line treatment with a CDK4/6 inhibitor in combination with an aromatase inhibitor for HR+/HER2- postmenopausal metastatic breast cancer (mBC) is considered as a standard of care based on the compelling data across all landmark trials. Methods: We report our experience about two cases with metastatic breast cancer treated by CDK4/6 inhibitor in combination with an aromatase inhibitor, which develop neuroendocrine differentiation. After observing an unusual massive progression, a biopsy of the metastasis was performed in both patients. Both histological analysis confirmed a lobular breast cancer with small cell neuroendocrine features and a high proliferation index (KI 67 90%). An NGS (Next generation sequencing) profile was realized on primary and metastatic tumors to detect new acquired genomic alterations. Results: The comparative analysis of the NGS results of primary and metastatic tumors revealed the occurrence of several events in both patients under treatment. For one patient, we identified new mutations in the genes CDH1, FANCG, PIK3CA, PTEN and TP53, which did not exist initially. For the second patient, we found an amplification of the segment containing FGFR1, CCND1, FGF4, FGF3, FADD genes and the deletion of the segment containing RB1 andTP53 genes. Such events were not observed on the primary tumor. Conclusions: Prostate adenocarcinoma may develop neuroendocrine features in later stages of castration-resistant prostate cancer but neuroendocrine differentiation is atypical in breast carcinoma. In case of unusual rapidly progressive disease after CDK4/6 inhibitor, biopsy of new metastases should be recommanded to search neuroendocrine differentiation, or druggable mutations to guide the treatment.