Case report: 18F-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

Abstract

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. ¹⁸F-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 ¹⁸F-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 ¹⁸F-FES PET/CT showed a new ER-positive pleural mass with multiple ER-negative pulmonary nodules. Since ¹⁸F-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 ¹⁸F-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 ¹⁸F-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).

Keywords: CDK4/6 inhibitor; FES PET/CT; estrogen receptor (ER); metastatic breast cancer; treatment response.

Figure 1

Chest CT. (A) Chest CT showed multiple pulmonary nodules in right lung and masses in right pleura (arrows) three years after surgery. (B) Followed-up chest CT revealed that pulmonary nodules increased in number, and pleural masses increased in size (arrows) when first-line CDK4/6i + endocrine therapy was started.

Figure 2

PET/CT. (A) ¹⁸F-FDG PET/CT showed mild FDG uptake of the largest pulmonary nodule (arrow, SUVmax 1.6) and increased FDG uptake of the multiple pleural masses (arrows, SUVmax 9.4). (B) Followed-up ¹⁸F-FDG PET/CT showed mild FDG uptake of the largest pulmonary nodule (arrow, SUVmax 1.2) and increased FDG uptake of the multiple pleural masses (arrows, SUVmax7.0). (C) Pulmonary nodule was negative on ¹⁸F-FES PET/CT (arrow), and multiple pleural masses showed obvious FES uptake (arrows, SUVmax 5.0). (D) Pulmonary nodule was negative on followed-up ¹⁸F-FESPET/CT (arrow), and multiple pleural masses showed different levels of FES uptake (arrows, SUVmax3.8).

Figure 3

Timeline of the patient’s disease progression.