[Paper-level Aggregated] PMCID: PMC7081042

Evidence Type(s): Oncogenic, Predictive, Prognostic

Justification: Oncogenic: The text indicates that mutations in the HER2 gene, such as S310F, S310Y, R678Q, D769H, and I767M, are associated with favorable outcomes and good responses to anti-HER2 therapy, suggesting their role in cancer progression. Predictive: The mention of specific HER2 mutations (e.g., L755S, D769Y) influencing the efficacy of treatments like neratinib and afatinib indicates their potential as predictive biomarkers for treatment response in HER2-positive breast cancer patients. Prognostic: The text discusses the association of HER2 overexpression with an aggressive phenotype and lower survival rates, indicating that certain mutations may have prognostic implications for patient outcomes.

Gene→Variant (gene-first): ERBB2(2064):D769H ERBB2(2064):D769Y ERBB2(2064):I767M EGFR(1956):K753I ERBB2(2064):L755S ERBB2(2064):R678Q ERBB2(2064):S310F ERBB2(2064):S310Y ERBB2(2064):V842I

Genes: ERBB2(2064) EGFR(1956)

Variants: D769H D769Y I767M K753I L755S R678Q S310F S310Y V842I

[Paragraph-level] PMCID: PMC7081042 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses how certain HER2 mutations, such as S310F, S310Y, R678Q, D769H, and I767M, correlate with favorable outcomes and good responses to anti-HER2 therapy, indicating their predictive value for treatment efficacy. Diagnostic: The passage mentions the identification of HER2 SNPs in HER2-positive breast cancer patients and their relationship with clinical outcomes, suggesting that these variants can be used to classify or define the disease subtype. Oncogenic: The passage indicates that somatic mutations in HER2 are linked to resistance to anti-HER2 therapy, suggesting that these mutations contribute to tumor development or progression.

Gene→Variant (gene-first): 2064:D769H 2064:D769Y 2064:I767M 1956:K753I 2064:L755S 2064:R678Q 2064:S310F 2064:S310Y 2064:V842I

Genes: 2064 1956

Variants: D769H D769Y I767M K753I L755S R678Q S310F S310Y V842I

[Paragraph-level] PMCID: PMC7081042 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses how certain HER2 mutations, such as S310F, S310Y, R678Q, D769H, and I767M, correlate with favorable outcomes and good responses to anti-HER2 therapy, indicating their predictive value for treatment efficacy. Diagnostic: The passage mentions the identification of HER2 SNPs in HER2-positive breast cancer patients and their relationship with clinical outcomes, suggesting that these variants can be used to classify or define the disease subtype. Oncogenic: The passage indicates that somatic mutations in HER2 are linked to resistance to anti-HER2 therapy, suggesting that these mutations contribute to tumor development or progression.

Gene→Variant (gene-first): 2064:D769H 2064:D769Y 2064:I767M 1956:K753I 2064:L755S 2064:R678Q 2064:S310F 2064:S310Y 2064:V842I

Genes: 2064 1956

Variants: D769H D769Y I767M K753I L755S R678Q S310F S310Y V842I