Combination of cyclin-dependent kinase 4/6 inhibitors and renin-angiotensin system inhibitors in breast cancer treatment: a promising therapeutic approach.

OBJECTIVE

The prognosis of metastatic breast cancer has improved with new targeted therapies like cyclin-dependent kinase 4/6 inhibitors. Renin-angiotensin system inhibitors, such as direct renin inhibitors, angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors are frequently used to manage hypertension and heart failure. However, recent research indicates that they may also provide potential benefits in cancer therapy. The combination of renin-angiotensin system inhibitors with cyclin-dependent kinase 4/6 inhibitors is an emerging area of interest in cancer research. Our hypotesis that, by inhibiting angiogenesis, renin-angiotensin system inhibitors may reduce tumor growth and improve the effectiveness of cyclin-dependent kinase 4/6 inhibitors by cutting off the supply of nutrients and oxygen to the tumor.

METHODS

Metastatic breast cancer patients treated with cyclin-dependent kinase 4/6 inhibitors were enrolled and retrospectively divided according to angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use: angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (+) and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (-). Progression-free survival and overall survival were defined as primary and secondary endpoints. The effect of categorized data on progression-free survival and overall survival was determined by Cox regression analyses.

RESULTS

Estimated median progression-free survival (HR 0.61, 95%CI 0.34-0.94; p = 0.041) and overall survival (HR 0.71, 95%CI 0.49-0.79; p: 0.01) were statistically significantly longer in the angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (+) group than in the angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (-) group.

CONCLUSION

Concomitant use of renin-angiotensin system inhibitors and cyclin-dependent kinase 4/6 inhibitors may have beneficial oncological effects in patients with breast cancer beyond their cardiovascular indications.