Episode Highlights
0:35 | Introduction
0:58 | Significance of ESR1 mutations in HR+ Metastatic Breast Cancer
2:20 | ESR1 testing in clinical practice
3:57 | When he recommends ESR1 testing
5:55 | About the SERENA-6 Trial (NCT04964934)
8:35 | Liquid vs tissue biopsy
10:25 | Discussing VAF
13:22 | Interpreting VAF
15:09 | What higher VAF mean for endocrine therapy resistance
16:36 | Utilizing ctDNA
19:20 | Differences between tissue and CtDNA results for ESR1
20:48 | Key resistance mechanisms with newer treatments targeting ESR1
23:21 | Key challenges
27:00 | Closing thoughts
In this episode of Targeted Talks, Seth Wander, MD, PhD, medical oncologist at Massachusetts General Hospital and assistant professor at Harvard Medical School, discusses the clinical importance of ESR1 mutations in hormone receptor (HR)-positive metastatic breast cancer and how these mutations influence treatment approaches.
ESR1 mutations, which make tumors resistant to aromatase inhibitors, are more frequently seen in advanced disease stages. Wander highlights how the recent FDA approval of the oral selective estrogen receptor degrader elacestrant (Orserdu), specifically for patients with estrogen receptor (ER)-positive/HER2-negative advanced or metastatic breast cancer, underscores the importance of ESR1 mutation testing in clinical practice.
“Because of the EMERALD study [NCT03778931], we learned that the oral selective estrogen receptor degrader elacestrant is particularly effective in [patients with] hormone receptor-positive metastatic breast cancer that have ESR1 alterations, and because of that, it is really important for clinicians to be looking for ESR1, particularly in patients that are progressing after standard antiestrogen therapy,” Wander says.
He then emphasizes that mutation testing via both solid and liquid biopsies is crucial for an accurate diagnosis and effective treatment planning, with liquid biopsy offering a less invasive option for ongoing monitoring.
One promising development in this area is the SERENA-6 trial (NCT04964934), which Wander describes as having the potential to reshape treatment strategies by focusing on patients with ESR1 mutations.
He also discusses the importance of understanding variant allele frequency (VAF) when interpreting these mutations. VAF is key for assessing disease biology and tumor burden, though interpreting these levels remains a challenge for many oncologists. Wander explains how high and low VAFs can impact treatment decisions, particularly as higher VAFs are often associated with endocrine resistance.
Here, Wander further delves into the practicalities and challenges of ESR1 mutation testing, the interpretation of VAF, and the future role of precision medicine in managing HR-positive metastatic breast cancer.
