CDK4/6 Inhibitor Therapy for Breast Cancer

(SIGNAL-ER 101 Trial)

This trial aims to determine if using ctDNA (a blood test that detects cancer DNA) can guide the optimal timing for starting a specific breast cancer treatment called CDK4/6 inhibitors, alongside hormone therapy. It targets individuals with early-stage breast cancer that is hormone receptor-positive (HR+) and HER2-negative, meaning the cancer grows with hormones and lacks excess HER2 protein. Participants will either begin CDK4/6 therapy based on ctDNA results or continue with hormone therapy alone, seeking to maintain treatment effectiveness while avoiding unnecessary medication. This study suits those who have undergone breast cancer surgery and meet specific tumor characteristics, such as being hormone receptor-positive without HER2 overexpression. As an unphased trial, it offers participants the chance to contribute to innovative research that could personalize the timing of breast cancer treatment.

The trial does not specify if you need to stop taking your current medications. However, you cannot use hormone replacement therapy while participating.

Research has shown that CDK4/6 inhibitors, such as ribociclib and abemaciclib, are generally well-tolerated by patients with HR+/HER2- breast cancer. Studies have found that these treatments can extend the time patients live without cancer spreading, and they typically do not cause severe side effects for most individuals. Specifically, trials with ribociclib and abemaciclib demonstrated that patients can live longer without disease progression, with manageable side effects.

Researchers are excited about CDK4/6 inhibitor therapy for breast cancer because it utilizes a personalized approach through ctDNA testing. Unlike standard treatments that rely solely on endocrine therapy, this method tailors treatment based on circulating tumor DNA results. This innovative approach allows for early intervention with ribociclib or abemaciclib when ctDNA is positive, potentially leading to more precise and effective cancer management. This strategy also minimizes unnecessary treatment for patients with negative ctDNA, reducing exposure to additional drugs and their side effects.

Research has shown that CDK4/6 inhibitors, such as ribociclib and abemaciclib, effectively treat early-stage breast cancer that is hormone receptor-positive (HR+) and HER2-negative (HER2-). Studies have found that combining these drugs with hormone therapy can extend the time patients live without cancer spreading. Specifically, trials like NATALEE and monarchE demonstrated better outcomes compared to hormone therapy alone. In this trial, participants with positive ctDNA results will begin CDK4/6 inhibitor therapy (ribociclib or abemaciclib) alongside standard endocrine therapy. Participants using these inhibitors had a lower risk of breast cancer recurrence. Overall, CDK4/6 inhibitors have improved survival rates and offer hope for better management of this breast cancer type.¹⁴⁶⁷⁸