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August 2, 2017Pharmacogenetics and Genomics

Six novel genetic loci were associated with a decline in LVEF in patients with HER2-positive breast cancer treated with combination chemotherapy and trastuzumab (P=7.73×10 to 8.93×10).

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Why the study?

Are specific single nucleotide polymorphisms (SNPs) associated with a decline in LVEF in patients with HER2-positive breast cancer treated with trastuzumab?

Population

1191 White, non-Hispanic patients with HER2-positive breast cancer from the NCCTG N9831 trial with available…

Comparison

Chemotherapy plus trastuzumab vs Chemotherapy only

Design

Cohort

Key result

Six novel genetic loci were associated with a decline in LVEF in patients with HER2-positive breast cancer treated with combination chemotherapy and trastuzumab (P=7.73×10 to 8.93×10).

Authors

DSDaniel SerieJCJulia E. CrookBNBrian M. Necela

Discussion

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Overview

Supports genetic risk for trastuzumab cardiotoxicity; leaves open clinical utility pending larger validation studies.

Key Points

  • To identify genetic markers associated with cardiotoxicity in patients receiving trastuzumab and chemotherapy.
  • Conducted a genome-wide association study on 1446 patients from the NCCTG N9831 trial.
  • Compared 618,863 SNPs to assess associations with decline in left ventricular ejection fraction.
  • Adjusted for factors including age, baseline LVEF, and antihypertensive medications.
  • Identified six loci associated with LVEF decline in patients receiving chemotherapy plus trastuzumab (P=7.73×10 to 8.93×10).
  • No significant associations found for SNPs related to trastuzumab-induced cardiotoxicity in chemotherapy-only group (arm A, N=391).
  • Confirmed associations with known SNPs related to anthracycline-induced cardiotoxicity at CBR3 and ABCB1.

Study Design

Type

Observational (n=1,446)

Structured PICO

Are specific single nucleotide polymorphisms (SNPs) associated with a decline in LVEF in patients with HER2-positive breast cancer treated with trastuzumab?

P
Population
1191 White, non-Hispanic patients with HER2-positive breast cancer from the NCCTG N9831 trial with available DNA passing quality control
I
Intervention
Chemotherapy plus trastuzumab (doxorubicin and cyclophosphamide followed by paclitaxel then trastuzumab, or concurrent paclitaxel and trastuzumab)
C
Comparator
Chemotherapy only (doxorubicin and cyclophosphamide followed by weekly paclitaxel)
O
Outcome
Decline in left ventricular ejection fraction (LVEF)safety

Main Result

p-value: p=7.73×10 to 8.93×10

This genome-wide association study identified six novel genetic loci associated with trastuzumab-induced cardiotoxicity in patients with HER2-positive breast cancer.

Cite This Study

Serie et al. (2017) conducted an observational in HER2-positive breast cancer (n=1,446). Trastuzumab plus chemotherapy vs. Chemotherapy only was evaluated on Decline in left ventricular ejection fraction (LVEF) (p=7.73×10 to 8.93×10). Six novel genetic loci were associated with a decline in LVEF in patients with HER2-positive breast cancer treated with combination chemotherapy and trastuzumab (P=7.73×10 to 8.93×10).

synapsesocial.com/papers/6a14e36d253bd9cd3ce62703https://doi.org/10.1097/fpc.0000000000000302
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