New Horizons in ESR1-Mutated Breast Cancer With Komal Jhaveri, MD, FACP

The recent FDA approval of imlunestrant represents a pivotal milestone in the treatment of patients with advanced or metastatic breast cancer and an ESR1 mutation, which is found in nearly half of patients who have taken hormone therapies and contributes to treatment resistance. In this interview, Dr. Komal Jhaveri, Breast Medical Oncologist at Memorial Sloan Kettering Cancer Center and lead author of the EMBER-3 trial, on which the approval was based shared her insights into the significance of the approval and its broader impact during Breast Cancer Awareness Month.

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Understanding Imlunestrant and Its Approval

Dr. Jhaveri began by explaining that imlunestrant is an oral selective estrogen receptor degrader (SERD) specifically developed to combat resistance mechanisms such as ESR1 mutations. These mutations, which can occur in up to 40% to 50% of metastatic estrogen receptor (ER)–positive breast cancers, represent a major challenge for current therapies. “Oral SERDS are thought to be very attractive because they’re well-tolerated and they can overcome the endocrine resistance of ESR1 mutation,” explained Dr. Jhaveri.

In the EMBER-3 trial, imlunestrant demonstrated significant benefit compared with physician’s-choice endocrine therapy in patients with ESR1-mutant tumors:

Median progression-free survival: 5.5 months in the imlunestrant arm and 3.8 months in the physician choice arm
Overall response rate: 14.3% in the imlunestrant arm and 7.7% in the investigator’s choice arm

While the benefit was not statistically significant in wild-type ESR1 tumors, imlunestrant still proved non-inferior, offering oncologists another valuable treatment option.

Impact on the Treatment Landscape

When considering the broader treatment landscape, the approval of imlunestrant provides welcome flexibility for both oncologists and patients. “As a community, we’re accustomed to having multiple options—whether CDK4/6 inhibitors, aromatase inhibitors, or antibody-drug conjugates (ADCs). Now, with imlunestrant joining lasofoxifene, we have another oral SERD option for ESR1-mutant tumors. Patients also find oral therapies preferable compared to injectable fulvestrant,” Dr. Jhaveri commented.

She also highlighted EMBER-3’s exploratory analysis of imlunestrant in combination with abemaciclib, which showed a median progression-free survival of 9.1 months in patients previously treated with CDK4/6 inhibitors, reinforcing the promise of future combination approvals.

Optimizing Biomarker Testing in Practice

Performing testing to identify which patients could benefit from imlunestrant remains central to clinical implementation. “After progression on a CDK4/6 inhibitor, our treatment selection is increasingly biomarker-driven,” Dr. Jhaveri emphasized. “Liquid biopsy has become an attractive, rapid option—not only to detect PI3K mutations but also ESR1 mutations, which guide use of oral SERDs like imlunestrant.” She underscored the importance of repeat testing across lines of therapy, as ESR1 mutations can emerge over time under selective therapeutic pressure.

Looking Forward During Breast Cancer Awareness Month

Reflecting on the significance of these advances during Breast Cancer Awareness Month, Dr. Jhaveri shared a hopeful, forward-looking message. “Breast Cancer Awareness Month is a reminder of how important it is for us to come together—not only to celebrate progress, but also to keep pushing forward. We must educate patients, nurses, fellows, and the broader community to promote screening, clinical trial awareness, and advocacy. Only then can we move closer to the ultimate goal of cure.”

Conclusion

The approval of imlunestrant is an important step forward in precision oncology, providing a new oral option for patients with ESR1-mutant, ER-positive breast cancer. Yet, as Dr. Jhaveri reminds us, much work remains to be done. “We’ve made remarkable progress, but there is still a lot of work ahead. These approvals show us how far we’ve come—and why it’s so critical to continue.”

About Dr. Jhaveri

Komal Jhaveri, MD, FACP, is a Breast Medical Oncologist and Section Head of the Endocrine Therapy Research Program in the Breast Medicine Service at Memorial Sloan Kettering Cancer Center. She is also the Clinical Director of the Early Drug Development Service. Dr. Jhaveri specializes in the treatment of breast cancer and leads clinical trials investigating novel therapeutics to improve patient outcomes.