Personalizing breast cancer treatment: CDK4/6 inhibitors, oral SERDs, and what's next

Treating hormone receptor (HR)–positive, HER2-negative breast cancer is increasingly about matching the right therapy to the right patient. Mayo Clinic oncologist Dr. Matthew Goetz explains that menopausal status, recurrence risk, and tolerability are the key levers guiding adjuvant endocrine therapy decisions. For postmenopausal patients, aromatase inhibitors remain the standard, while premenopausal patients at higher risk are increasingly receiving aromatase inhibitors plus ovarian function suppression — though tamoxifen remains a valid option for lower-risk patients who can't tolerate the side effects.

CDK4/6 inhibitors abemaciclib and ribociclib have earned their place in adjuvant regimens for higher-risk patients, backed by long-term data from the monarchE and NATALEE trials showing sustained disease-free survival benefits — and, in monarchE's case, a reduction in the risk of death. In the metastatic setting, CDK4/6 inhibitors remain the first-line standard, though oral SERDs like giredestrant and camizestrant have so far failed to outperform aromatase inhibitors when combined with CDK4/6 inhibitors.

Key Takeaways

• Abemaciclib is FDA-approved for adjuvant use in high-risk HR+ breast cancer (≥4 positive lymph nodes, or 1–3 nodes with grade 3 disease or large tumor size)
• The phase 3 lidERA trial showed giredestrant reduced invasive disease risk by ~30% vs. standard endocrine therapy — a larger effect than anticipated
• Oral SERDs (giredestrant, camizestrant) have not shown PFS benefit over aromatase inhibitors when combined with CDK4/6 inhibitors in the metastatic setting

Why it matters: With giredestrant potentially nearing FDA approval, clinicians may soon have a more potent oral option for ER-targeted therapy — reshaping how adjuvant treatment is escalated for HR+ breast cancer patients.