ERBB2 alterations a new prognostic biomarker in stage III colon cancer from a FOLFOX based adjuvant trial (PETACC8)

Laurent‐Puig, Pierre; Balogoun, Ralyath; Cayre, Anne; Malicot, Karine Le; Tabernero, J.; Mini, Enrico; Folprecht, Gunnar; Laethem, J. Van; Thaler, Josef; Petersen, Lone; Sanchez, Eduardo Vilar; Bridgewater, John; Ellis, Stephen B.; Locher, Clara; Lagorce, Christine; Ramé, J-F.; Lepage, Côme; Penault‐Llorca, Frédérique; Taieb, Julien

doi:10.1093/annonc/mdw370.08

Cited by 33 publications

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“…Thus, we designed this study in Chinese population to explore the relationship between HER2 amplification and BRAF mutation and clinicopathological parameters, and to evaluate prognostic and predictive values of HER2 amplification and BRAF mutation for CRC. In our study, the HER2 gene amplification rate is 5.63%, similar to some other studies (Hyman et al, 2018;Jeong et al, 2016;Laurentpuig et al, 2016;Richman et al, 2016). However, report from Korea (Dong et al, 2007) showed the protein expression rate was 47%.…”

Section: Discussionsupporting

confidence: 89%

“…No evidence has convinced that HER2 gene amplification is a prognostic factor for CRC. Laurentpuig et al (2016) and Stahler et al (2017) demonstrated patients with HER2 amplification tumor had a worse survival, but some recent studies (Pietrantonio et al, 2017;Richman et al, 2016) argued no meaningful relationships between this marker and survival. Several studies had reported the frequency of BRAF mutation in Chinese CRC patients, but the number of samples was limited in most of the studies (Li et al, 2011a; Mao et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Li et al (2011b) reported an association between HER2 expression and tumor size and distant metastases, and a recent meta-analysis showed HER2 amplification was associated with lymph node metastasis and advanced tumors stage (Sun et al, 2016). The number of studies suggests that HER2 may play some role in tumor progression and would be a valuable prognostic factor for CRC patients (Laurentpuig et al, 2016;Stahler et al, 2017). But in other studies, HER2 gene amplification was higher in patients with more advanced stage or distant metastases, and no significant difference in prognosis for CRC patients (Pietrantonio et al, 2017;Wang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…The prognostic value of HER2 amplification in CRC patients has been widely investigated, but no rationale had been obtained. A study from Germany indicated that HER2 amplification resulted in poorer prognosis in all stage CRC (Ingold Heppner et al, 2014), and Laurentpuig et al (2016) found that HER2 amplification was significantly associated with worse prognosis in patients with stage III CRC. Moreover, some studies showed patients with HER2 wild-type tumors have positive OS compared with those tumors containing amplified HER2 due to benefit from anti-EGFR monoclonal antibody, and the targeted management may be an influential factor in patients with advanced CRC (Pietrantonio et al, 2017;Salvia, Lopez-Gomez & Garcia-Carbonero, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, information about HER2 amplification in Chinese CRC patients was limited (Li et al, 2011b). Some studies (Laurentpuig et al, 2016;Stahler et al, 2017) demonstrated patients with HER2 amplification tumor had a worse survival, but other studies (Pietrantonio et al, 2017;Richman et al, 2016) argued no meaningful relationships between this marker and survival. Therefore, in the present study, we analyzed the HER2 amplification and BRAF V600E mutation status of CRC patients to evaluate possible associations between HER2 and BRAF V600E mutation and the clinicopathological characteristics in primary stage I-III CRC, and we also attempted to explore the prognostic role of HER2 and BRAF V600E mutation.…”

Section: Introductionmentioning

confidence: 99%

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HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China

Zhang

Wang

et al. 2020

PeerJ

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Objective To investigate the frequency and prognostic role of the human epidermal growth factor receptor 2 gene (HER2) and BRAF V600E gene mutation in Chinese patients with colorectal cancer (CRC). Methods Clinicopathological and survival information from 480 patients with stage I–III CRC were reviewed and recorded. HER2 amplification was analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), BRAF V600E mutation was tested by IHC and Sanger sequencing. The relationship between HER2 and BRAF V600E mutation status and clinicopathological characteristics and outcomes were determined. Results The amplification of HER2 and BRAF V600E mutation were identified in 27 of 480 (5.63%) and 19 of 480 (3.96%) CRC patients, respectively. HER2 amplification significantly correlated with greater bowel wall invasion (P = 0.041) and more advanced TNM stage (I vs. II vs. III; 0 vs 5.78% vs. 7.41%, P = 0.013). Patients suffering from tumors with poor differentiation had a higher incidence rate of BRAF V600E mutation than those with moderate/well differentiation (7.77% vs 2.92%, P = 0.04). HER2 amplification was an independent prognostic factor for worse disease-free survival (DFS) (HR = 2.53, 95% CI: 1.21–5.30, P = 0.014). Conclusion The prevalence of HER2 amplification and BRAF V600E mutation in stage I–III CRC patients in Chinese was 6% and 4%, respectively, and HER2 amplification appeared to be associated with a worse DFS. More comprehensive molecular classification and survival analysis are needed to validate our findings.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China

Zhang

Wang

et al. 2020

PeerJ

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Molecular Markers Beyond Microsatellite Instability for Assessing Prognosis in Early-Stage Colorectal Cancer

Sartore-Bianchi

2017

JAMA Oncol

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Diagnosis and Treatment of ERBB2-Positive Metastatic Colorectal Cancer

et al. 2022

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Amplification of ERBB2 (formerly referred to as HER2) is present in nearly 3% of patients with metastatic colorectal cancer overall and 5% of patients with KRAS and NRAS wild-type tumors. Despite the availability of several ERBB2-targeted therapeutic options for patients with ERBB2-positive breast and gastric/gastroesophageal tumors, to date, there are currently no approved therapies for patients with ERBB2-positive metastatic colorectal cancer, although ERBB2-targeted therapies are recommended in National Comprehensive Cancer Network guidelines. Recent evidence indicates that anti-ERBB2 therapeutic strategies are active in patients with ERBB2-positive metastatic colorectal cancer and could potentially represent a new standard-of-care.OBSERVATIONS The protein ERBB2 is a member of a family of epidermal growth factor receptors that also includes epidermal growth factor receptor (ERBB1), ERBB3, and ERBB4. Amplification of ERBB2 leads to overexpression of the ERBB2 tyrosine kinase receptor, resulting in aberrant signaling and cell migration, growth, adhesion, and differentiation. Colorectal tumors that harbor ERBB2 amplification are more likely to originate on the left side of the colon, are associated with primary and acquired resistance to anti-epidermal growth factor receptor therapies, and have increased incidence of central nervous system metastases. Using immunohistochemistry, fluorescence in situ hybridization, next-generation sequencing, and liquid biopsy techniques, several randomized clinical trials have evaluated the efficacy of ERBB2-targeted therapies in patients with ERBB2-positive metastatic colorectal cancer. These therapies include monoclonal antibodies, antibody-drug conjugates, and tyrosine kinase inhibitors, many of which were associated with favorable efficacy and safety profiles when treating patients with ERBB2-positive metastatic colorectal cancer. CONCLUSIONS AND RELEVANCEThe results of this review suggest the ERBB2 receptor is a promising target for patients with metastatic colorectal cancer; however, to date, no therapies are approved for use in this patient population. Therefore, it is imperative to continue to work to address this unmet need so that patients with ERBB2-positive metastatic colorectal cancer have therapeutic options should they become refractory to treatment with standard therapies.

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ERBB2 alterations a new prognostic biomarker in stage III colon cancer from a FOLFOX based adjuvant trial (PETACC8)

Cited by 33 publications

References 0 publications

HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China

HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China

Molecular Markers Beyond Microsatellite Instability for Assessing Prognosis in Early-Stage Colorectal Cancer

Diagnosis and Treatment of ERBB2-Positive Metastatic Colorectal Cancer

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