Choosing Among Oral SERDs for Treating ESR1-Mutant Breast Cancer and Final Takeaways for Clinical Practice

In this final segment, Drs. Mouabbi and Bardia explore how clinicians might differentiate among multiple oral SERD options when efficacy appears broadly comparable, focusing instead on tolerability, lifestyle considerations, and safety. Using the example clinical case as a framework, they set aside elacestrant and compare imlunestrant and camizestrant as hypothetical monotherapy choices.

Dr. Bardia emphasizes that when several reasonable options exist, lifestyle factors become decisive. Imlunestrant is associated primarily with lower gastrointestinal toxicity, particularly diarrhea, which could significantly interfere with a patient who travels frequently. Camizestrant, in contrast, is associated with bradycardia and transient visual disturbances such as photopsia. Although these visual symptoms may initially be noticeable, especially in low-light situations, patients often adapt over time, and they generally have less impact on day-to-day functioning and travel. For this reason, camizestrant may be preferable for a patient prioritizing mobility and flexibility.

The discussion also revisits combination strategies, noting that if available, giredestrant plus everolimus could represent an attractive option due to its largely asymptomatic bradycardia and minimal impact on quality of life compared with diarrhea-prone regimens. This reinforces the recurring theme of aligning treatment choice with patient priorities rather than relying solely on efficacy metrics.

Safety considerations around cardiac effects are also addressed. Dr. Mouabbi raises questions about combining oral SERDs associated with bradycardia with ribociclib, which requires QT interval monitoring. Dr. Bardia notes that although formal safety data are still emerging, the differing mechanisms, heart rate effects versus QT prolongation, make clinically significant overlap unlikely, and he does not anticipate major barriers to such combinations.

The segment concludes with the message that routine molecular testing is essential. Identifying ESR1 and other actionable mutations enables optimal use of emerging oral SERDs and ensures that patients receive the most appropriate, targeted therapy.