Breast
non-CME
Anna D. Louie, MD (she/her/hers)
General Surgery Resident
Duke University, United States
Disclosure information not submitted.
Anna D. Louie, MD (she/her/hers)
General Surgery Resident
Duke University, United States
Disclosure information not submitted.
Rani Bansal, MD
Assistant Professor of Medicine
Duke University, United States
Disclosure information not submitted.
Sharon Wu, PhD
Senior Research Scientist, Clinical and Translational Research
Caris Life Sciences, United States
Disclosure information not submitted.
Marzia Capelletti, PhD, MMSc
Director, Molecular Science Liaisons
Caris Life Sciences, United States
Disclosure information not submitted.
W. Michael Korn, MD
Chief Medical Officer
Caris Life Sciences, United States
Disclosure information not submitted.
Virginia Kaklamani, MD, DSc
Professor of Medicine
University of Texas Health Sciences Center, United States
Disclosure information not submitted.
Antoinette Tan, MD, MHSc, FACP
Chief of Breast Medical Oncology
Levine Cancer Institute, Atrium Health, United States
Disclosure information not submitted.
Pavani Chalasani, MD, MPH
Associate Professor of Medicine
University of Arizona Cancer Center, United States
Disclosure information not submitted.
Wafik S. El-Deiry, MD, PhD, FACP
Director, Cancer Center at Brown University, Director, Joint Program in Cancer Biology,
Legorreta Cancer Center of Brown University, United States
Disclosure information not submitted.
Don Dizon, MD, FACP, FASCO
Professor of Medicine, Professor of Surgery
Legorreta Cancer Center of Brown University, United States
Disclosure information not submitted.
Stephanie L. Graff, MD
Director of Breast Oncology
Lifespan Cancer Institute, United States
Disclosure information not submitted.
Prevalence of known pathogenic mt of PIK3CA in primary BCTs was 30.5% (n=1529). Further, metastatic sites enriched for the HR+/HER2- subtype had increased prevalence of PIK3CA-mt compared to primary BCT: gastrointestinal (GI: PIK3CA mt 50.4%), gynecologic (Gyn: 47.7%), bone (42.0%), and liver (36.7%) (all q < 0.001).
Hierarchical clustering showed Gyn, GI, and peritoneum/omentum (PO) metastases clustered in a separate clade and had frequent CDH1-mt (Overall: 8.9%, GI: 62.9%, PO: 45.7%, Gyn: 42.1%; q < 0.005). These sites were also enriched in lobular histology (Overall: 6.2%, GYN: 25.4%, GI: 30.4%, P/O: 27.8%).
PIK3CA-mt/CDH1-wt did not confer a significant prognostic advantage over PIK3CA-mt/CDH1-mt (n=774 vs 3366, p=0.15). But patients who were PIK3CA-mt and CDH1-mt had significantly worse post-Alpelisib survival compared to those who were PIK3CA-mt but CDH1-wt (n=69 vs 294; 258 vs >700 days, median survival not reached), hazard ratio: 1.69, 95% CI (1.09-2.61), p=0.017) (Fig 1).
Conclusions: Patients treated with Alpelisib with concurrent PIK3CA and CDH1 mt had significantly worse survival than patients who were PIK3CA-mt/CDH1-wt. This finding warrants further investigation, as it may predict benefit from PI3Kis. A possible mechanism involving cadherin switch as a downstream effect of PIK3CA hyperactivation should be explored.