Positive predictive value of ERBB2 copy number gain by tissue or circulating tumor DNA next-generation sequencing across advanced cancers
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Ami N. Shah1, Ashwin Sunderraj1, Brian Finkelman2, Sharlene H. See1, Andrew A. Davis3, Lorenzo Gerratana4, Firas Wehbe1, Neelima Katam1, Deva Mahalingam1, William J. Gradishar1, Amir Behdad1, Luis Blanco1 and Massimo Cristofanilli1
1 Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA
2 Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
3 Siteman Cancer Center of Washington University, St. Louis, MO, USA
4 Department of Medical Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy
|Ami N. Shah,||email:||email@example.com|
Keywords: ERBB2; HER2; next-generation sequencing; copy number gain; circulating tumor DNA
Received: November 30, 2021 Accepted: January 10, 2022 Published: February 02, 2022
Background: The correlation of ERBB2 copy number gain (CNG) from tissue or circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) with standard HER2 tissue evaluation is not well understood.
Materials and Methods: We retrospectively identified patients with ERBB2 CNG on commercial NGS. We described their clinical-pathologic features and calculated the positive predictive value (PPV) of ERBB2 CNG by NGS for HER2-positivity by IHC and FISH testing.
Results: 176 patients had NGS revealing an ERBB2 CNG (112 by tumor tissue and 91 by ctDNA). The cancer subtypes with the most cases with ERBB2 CNG by NGS were breast (n = 67), non-small cell lung (n = 25), colorectal (n = 18), gastroesophageal (n = 17), pancreatic (n = 11), and uterine (n = 11). The PPV of ERBB2 CNG in determining HER2 positivity by standard IHC/FISH definitions was 88% for tissue NGS (n = 57) and 80% for ctDNA (n = 47). The PPV among breast cancer patients for tissue NGS was 97% (n = 35) and ctDNA was 93% (n = 39). However, for non-breast cancer cases, the PPV of ERBB2 amplification by tissue NGS dropped to 76% (n = 22) and by ctDNA to 44% (n = 7).
Conclusions: ERBB2 CNG by NGS is detected in numerous malignancies for which HER2 testing is not standard. Detection of ERBB2 CNG by tissue NGS and ctDNA has a high PPV for true HER2-positivity by standard IHC and/or FISH testing in breast cancer.
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