Pre-existing and emerging immune-mediated diseases in patients with breast cancer undergoing cyclin-dependent kinases 4/6 inhibitors and endocrine therapy.

BACKGROUND

CDK4/6 inhibitors (CDK4/6i) are cornerstone therapies in Hormone Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Breast Cancer (BC) and emerging evidence suggests that they may influence immune function, potentially enhancing antitumor immunity but also triggering autoimmune reactions. This study aims to investigate the prevalence of autoimmune diseases (AD) in patients with HR+/HER2- BC to identify potential predictive biomarkers and to assess the impact of AD on disease progression.

PATIENTS AND METHODS

This retrospective-prospective cohort study included consecutive HR+/HER2- BC patients treated with CDK4/6i at Humanitas Research Hospital. Clinical-pathological features, treatment data, AD occurrence, and blood test values were collected. Descriptive statistics were used to determine AD prevalence, Kaplan-Meier method to estimate progression-free survival (PFS), and log-rank test to compare survival curves.

RESULTS

352 patients (median age: 54 years) were enrolled, of which 87.2% had metastatic disease and received palbociclib, abemaciclib, or ribociclib (45.2%, 31.0%, and 23.9%, respectively). 12.8% of patients had early BC and received abemaciclib. ADs were identified in 49 patients: most had pre-existing conditions (38 stable and 4 flaring during treatment) while 7 developed new-onset ADs. The most frequent AD were Hashimoto thyroiditis, vitiligo, and rheumatoid arthritis. In the metastatic setting, the median PFS was significantly longer in patients with AD compared to those without (P = .0013), with patients with flaring or new-onset AD showing a better PFS (P = .0015). No significant predictive biomarkers for AD evolution were found.

CONCLUSION

CDK4/6i therapy is feasible in patients with pre-existing AD. Interestingly, the onset or flaring of AD during treatment is associated with improved PFS, suggesting a potential immune activation induced by CDK4/6i. However, further robust and prospective studies are required to validate these findings and explore the underlying mechanisms.