Poster Spotlight Session 9: Exploiting Tumor Biology in HER2-positive Breast Cancer to Escalate or De-escalate Neoadjuvant Therapy
Wednesday, December 6 • 5:30 p.m. – 6:30 p.m. • Stars at Night Ballroom 1-2
Presentation: Genomic characterization of endocrine resistance in ER+HER2+ breast cancers in the POETIC Trial
Maggie Chon U Cheang, PhD
The Institute of Cancer Research,
London, England
What is your presentation about?
We want to improve our understanding of both intrinsic and adaptive mechanisms for endocrine resistance in ER+HER2+ breast cancers. We studied both genomic and spatial transcriptomics and proteomics in both baseline and on-treatment good and poor responders to aromatase inhibitors. We had previously found that intrinsic HER2-enriched molecular subtype at baseline predicts poor early biological response, defined by high on treatment Ki67 level. In this study, we went deep on some interesting cases, and we have found a subset of ER+HER2+ samples that are HER2-enriched with TP53 mutations having good response to aromatase inhibitors and clinical outcome, while in other tumors TP53 mutation is associated with poor response, consistent to what we observed within ER+HER2- tumours. Our spatial biology data points to intratumoral and intertumoral heterogeneity that varies between good and poor responders.
What makes this topic important in 2023?
It has long been known that overall, there is impeded anti-proliferative response of HER2+ breast cancer to endocrine therapy. Many anti-HER2 therapies are now available and might be felt to negate the importance of this relationship. However, while anti-HER2 therapy is given for 1 year in primary breast cancer patients (including the patients participating in the POETIC trial), endocrine therapy is given for at least 5 years. Thus, any residual HER2+ disease after the anti-HER2 therapy remains at risk of an incomplete endocrine response. By exploring how endocrine therapy works in HR+HER+ tumour in highly personalised fashion we expect to be able to provide supporting evidence for scientists to identify newer or alternative approved drugs which have the maximum potential to prevent disease returning in the future.
HER2-Enriched subtype and immune components are typically considered features associated with sensitivity to anti-HER2 treatments. Cross talk between ER and HER2 has been implicated in both response and resistance to therapy. The uniqueness of our study is that we are performing in-depth molecular characterization of the tumours showing differential early biological response to AI prior to receiving their standard of care treatment including anti-HER2 agents as needed. By exploring how endocrine therapy works in HR+HER+ tumour in highly personalized fashion we expect to be able to provide supporting evidence for scientists to identify newer or alternative approved drugs which have the maximum potential to prevent disease returning in the future.
How did you get involved in this particular area of breast cancer research, care, or advocacy?
When I was young, I always loved to read detective stories like Sherlock Holmes and discovered I had a passion for solving cases. I even applied for a job in a forensic laboratory after my first degree in genetics!
I started to work in the field of cancer research because cancer has affected my family, and this sparked an interest in learning about this disease.
The more I learn, especially about the molecular profile of cancer, I find myself a step further to revealing the “mystery”!