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Published on: July 25, 2020
Clinical and molecular characterization of HER2 amplified-pancreatic cancer
Angela Chou1, Nicola Waddell2, Mark J Cowley3
1Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; Anatomical Pathology, Sydpath, St Vincent's Hospital, Sydney, Australia ; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
Background:
Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.
Methods:
HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).
Results:
An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2- amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is >22,000 per annum.
Conclusions:
HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.
Insights
HER2 amplification occurs in 2% of pancreatic ductal adenocarcinoma (PDAC) cases, presenting unique clinical features. This finding supports exploring anti-HER2 therapies for this lethal cancer, offering new treatment avenues.
Area of Science:
- Oncology
- Genomics
- Cancer Therapeutics
Background:
- Pancreatic cancer (PDAC) is a highly lethal and molecularly diverse malignancy.
- Repurposing targeted therapies is a promising strategy for improving outcomes.
- HER2 amplification in PDAC is not well-characterized, limiting anti-HER2 therapy potential.
Purpose of the Study:
- To characterize HER2 amplification in pancreatic ductal adenocarcinoma.
- To establish diagnostic criteria for HER2 amplification in PDAC.
- To explore the clinical implications of HER2 amplification in PDAC.
Main Methods:
- Detected and analyzed HER2 amplification using multiple genomic sequencing approaches.
- Defined HER2 amplification in 469 PDAC patients using standardized reference laboratory assays.
Main Results:
- Identified an amplified inversion event at the HER2 locus in a PDAC patient.
- Established diagnostic criteria for HER2 amplification in PDAC, with a prevalence of 2%.
- HER2-amplified PDAC showed a lack of liver metastases and a higher incidence of lung and brain metastases.
Conclusions:
- HER2 amplification occurs in 2% of PDAC and has distinct clinical features.
- The 2% incidence of HER2-amplified PDAC is an attractive target for anti-HER2 therapies due to limited treatment options.
- Patient recruitment for anti-HER2 therapy trials based on HER2 amplification could enhance feasibility for less common cancer types.
