Case report: (18)F-FES PET/CT predicted treatment responses of second-line and third-line CDK4/6 inhibitors after disease progression on first-line CDK4/6 inhibitor in a HR+/HER2- metastatic breast cancer patient

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) has become the commonest first-line treatment of hormonal receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, therapy is quite individualized after progression of disease (PD) when CDK4/6i fails. Estrogen receptor (ER) status of metastatic lesions of bone, lung or liver might be different from the primary tumor and biopsy of metastatic lesions was invasive and not always available. Prediction of treatment response after PD of CDK4/6i remains unsolved. (18)F-fluoroestradiol (FES) PET/CT could non-invasively reveal ER expression both in primary and metastatic breast cancer and recognize heterogeneity of ER status. CASE PRESENTATION: A 70-year-old woman with Parkinson’s disease, osteoporosis and cardiovascular co-morbidity was diagnosed with HR+/HER2- breast cancer (pT2N2M0, stage IIIa). Three years later, she developed metastases in right lung and pleura with pleural effusion and received palbociclib + letrozole. After 8 months the disease progressed, and (18)F-FES PET/CT revealed multiple ER-positive pleural lesions and ER-negative pulmonary nodules after PD and the progression-free survival (PFS) of first-line CDK4/6i was 8 months. Since most of the metastatic lesions were ER-positive, abemaciclib + fulvestrant were chosen as the second-line CDK4/6i treatment and the PFS was 15 months. Another (18)F-FES PET/CT showed a new ER-positive pleural mass with multiple ER-negative pulmonary nodules. Since (18)F-FES PET/CT revealed that the dominant lesions were still ER-positive, dalpiciclib + exemestane + fulvestrant were prescribed as the third-line CDK4/6i treatment. Currently the patient’s disease had been stable for 2 months. CONCLUSION: This case demonstrated that (18)F-FES PET/CT could show ER heterogeneity non-invasively and reveal the treatment responses a predictive imaging tool of serial second- and third-line of CDK4/6i treatments when first-line CDK4/6i failed in HR+/HER2- MBC. So long as the dominant or newly-developed metastatic lesion was ER-positive on (18)F-FES PET after first-line CDK4/6i, the patient might show certain therapeutic response towards endocrine-based treatment including second- and third-line of CDK4/6i, and thus increased the time to chemotherapy (TTC).