Prognostic Significance of Pretreatment ¹⁸F-FDG PET/CT Parameters in Patients With ER+/HER2- Metastatic Breast Cancer Treated With CDK4/6 Inhibitors Plus Endocrine Therapy.

OBJECTIVE

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy (ET) constitute the standard systemic treatment for estrogen receptor-positive, human epidermal growth factor 2-negative (ER+/HER2-) metastatic breast cancer (MBC). However, treatment responses remain heterogeneous, highlighting the need for reliable prognostic markers. This study aimed to evaluate the prognostic significance of ¹⁸F-fluorodeoxyglucose (FDG) PET/CT findings in this setting.

MATERIALS AND

METHODS

This retrospective single-center cohort study included patients with ER+/HER2- MBC who underwent ¹⁸F-FDG PET/CT before initiating CDK4/6 inhibitors plus ET between 2018 and 2023. Maximum standardized uptake value (SUVmax), whole-body metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. Progression-free survival (PFS) and overall survival (OS) were evaluated as the primary and secondary outcomes, respectively, using multivariable Cox models. PET parameters (SUVmax, MTV, and TLG) were analyzed as both continuous and dichotomized variables based on median values, adjusting for relevant clinical covariates.

RESULTS

Among the 374 patients, 82 (21.9%) presented with de novo metastatic disease, and 357 (95.5%) received CDK4/6 inhibitors as first-line therapy. In multivariable Cox analysis, all continuous PET parameters were independently associated with PFS (adjusted hazard ratio for SUVmax 1.05 [95% confidence interval 1.02-1.08]; log-transformed MTV 1.16 [1.08-1.25]; and log-transformed TLG 1.14 [1.07-1.23]) and OS (SUVmax 1.08 [1.04-1.11]; log-transformed MTV 1.24 [1.12-1.38]; and log-transformed TLG 1.22 [1.11-1.34]) with all P < 0.001. Results based on dichotomized PET parameters were similar to those obtained with continuous values: PFS (adjusted hazard ratio for SUVmax ≥ 7.6, 1.41 [1.08-1.85]; MTV ≥ 21.2 cm³, 1.41 [1.08-1.86]; and TLG ≥ 78.9, 1.51 [1.14-1.99]) with P ≤ 0.013 and OS (1.43 [1.01-2.04]; 1.84 [1.28-2.66]; and 1.73 [1.20-2.50], respectively) with P ≤ 0.046.

CONCLUSION

Pretreatment ¹⁸F-FDG PET/CT parameters are independent prognostic markers in patients with ER+/HER2- MBC receiving CDK4/6 inhibitors with ET, supporting their potential utility in risk stratification.