Tolerability, Adherence, and Practical Use of Oral SERDs for ESR1-Mutant Breast Cancer in Clinical Practice

In this segment, Drs. Mouabbi and Bardia focus on the tolerability, side effect profiles, and real-world practicality of oral SERDs. Dr. Mouabbi opens with a clinical observation from practice, noting that patients who transition to oral SERDs frequently describe a “night and day” improvement in tolerability compared with prior endocrine therapies. This consistent patient-reported experience highlights the growing importance of quality of life and long-term adherence as these agents move earlier in treatment paradigms.

Dr. Bardia reviews the expanding landscape of oral SERDs and related agents, emphasizing that differences in trial design and combination strategies help guide clinical use. Elacestrant and imlunestrant were studied as single agents, with elacestrant most commonly associated with upper gastrointestinal symptoms such as nausea, and imlunestrant more frequently causing lower gastrointestinal effects, particularly diarrhea. Other agents, including giredestrant and camizestrant, were primarily studied in combination regimens. Giredestrant demonstrated benefit when combined with everolimus, while camizestrant was evaluated in a CDK4/6 inhibitor switch strategy. Emerging agents such as vepdegestrant introduce alternative mechanisms of estrogen receptor targeting and appear generally well tolerated, with mild myelosuppression noted in early studies.

Unique adverse events are also discussed, including bradycardia seen with giredestrant and camizestrant, and transient visual disturbances associated with camizestrant, typically described as light adaptation phenomena. Importantly, these side effects are generally manageable and reversible.

Drawing from early-stage data, the speakers note that oral SERDs are associated with substantially lower rates of treatment discontinuation due to arthralgias and vasomotor symptoms compared with aromatase inhibitors. This improved tolerability suggests better adherence and sustained disease control over time.

The segment concludes with a practical discussion on integrating molecular testing into busy community practices. Dr. Bardia emphasizes that waiting 7–10 days for mutation results is unlikely to compromise outcomes in most patients with ER-positive disease and allows clinicians to select the most appropriate, biology-driven therapy rather than initiating treatment prematurely.