Developing Story: What Biomarkers Tell Us with Dr. Neil Vasan
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Live from Stage 4 | Episode #043 | 08/25/2026 | Developing Story
GUEST
Dr. Neil Vasan, MD, PhD, is a distinguished breast oncologist, physician-scientist, and the Director of Translational Research in Breast Cancer at NYU Langone Health. Armed with an Ivy League background—including degrees from Harvard and Yale—he has dedicated his career to bridging the gap between laboratory discovery and patient care. Dr. Vasan’s groundbreaking research famously identified double PIK3CA mutations as an oncogenic biomarker, a discovery that has successfully transitioned from bench to bedside to guide target treatments. In addition to running the Vasan Lab and treating patients, he serves as an Acting Chair and Standing Member of the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC), positioning him at the absolute forefront of evaluation for next-generation cancer therapies.
Quick Summary
Biomarkers are reshaping breast cancer care, but understanding what they measure is key. This episode breaks down three essential types: DNA biomarkers that identify genetic mutations, RNA biomarkers that reveal which genes are active in your tumor, and protein biomarkers like HER2 and PD-L1 that show what's actually happening at the cellular level. Learn why this distinction matters for treatment decisions and how emerging liquid biopsy platforms are making real-time tumor monitoring more accessible
Key Topics Covered
DNA biomarkers reveal genetic mutations and structural changes in the tumor's genome (like BRCA1/BRCA2) — they show what's in the blueprint.
RNA biomarkers measure which genes are actively expressed in your specific tumor — they show what's actually turned on.
Protein biomarkers reflect the functional output of gene activity (HER2, PD-L1) — they show what the tumor is doing.
PD-L1 is a predictive biomarker that helps determine if immunotherapy checkpoint inhibitors are likely to work for your tumor.
PD-L1 expression varies — it can be heterogeneous within the same tumor, and how it's scored depends on the assay and antibody used, making it an imperfect but clinically meaningful measurement.
In triple-negative breast cancer, PD-L1 status directly influences treatment selection decisions.
Liquid biopsy platforms are making it easier to monitor tumors through blood tests and enrolling patients nationwide in real-time research studies.
Understanding which layer of biology your biomarker testing is measuring — DNA, RNA, or protein — helps you ask better questions about what results mean for your treatment plan.
Clinical Trials Cited
SERENA-6 — Studied ESR1 mutations and oral selective estrogen receptor degraders (SERDs) for response prediction in metastatic breast cancer
TBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial)
TBCRC 048 (olaparib expanded) expansion cohorts: Phase 2 study of olaparib monotherapy in patients with metastatic breast cancer (MBC) with germline mutations in PALB2 or somatic mutations in BRCA1 or BRCA2 - Dr. Nadine Tung Clinical trial information: NCT02032823.
ReDiscover-2 - Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer NCT06982521
KEYNOTE-522Pembrolizumab for Early Triple-Negative Breast Cancer
lidERA Breast Cancer — A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer NCT04961996
the PREDICT-DNA trial— Circulating tumor DNA, pathologic response after neoadjuvant therapy, and survival: TBCRC 040 Clinical trial information: NCT02743910.
Genes & Biomarkers Mentioned
BRCA1, BRCA2 (DNA biomarker, germline, high penetrance)
PALB2 (DNA biomarker, germline, high penetrance gene)
TP53 (DNA biomarker, germline, high penetrance gene) Inherited changes in TP53 point to Li-Fraumeni syndrome, a rare condition that raises the lifetime risk for many types of cancer
ATM, CHEK2 (DNA biomarker, germline, moderate penetrance genes)
PIK3CA (DNA biomarker, truncal, somatic mutation, ~40% of breast cancers)
ESR1 (DNA biomarker, drug resistance mutation, subclonal (acquired) somatic mutation, -20% of metastatic breast cancer)
PD-L1 (protein biomarker, important in triple-negative breast cancer)
ER, PR, HER2 (protein biomarker, receptor status)
Drugs Mentioned
PARP inhibitors (olaparib, rucaparib, talazoparib)
CDK4/6 inhibitors
Alpelisib, capivasertib (PIK3CA inhibitors)
Elacestrant, imlunestrant, vepdegestrant (oral SERDs)
Gedatolisib (sold under the brand name Revtorpyk(approved July 14, 2026) (dual PI3K/mTOR inhibitor)
T-DXd (HER2-targeted therapy, now in adjuvant setting)
Pembrolizumab
