0000000000598049
AUTHOR
Hans Wildiers
Abstract PD1-05: Latest findings from the breast cancer cohort in SUMMIT - a phase 2 ‘basket’ trial of neratinib + trastuzumab + fulvestrant for HER2-mutant, hormone receptor-positive, metastatic breast cancer
Abstract Background: HER2 mutations are oncogenic in hormone receptor positive (HR+) metastatic breast cancer (MBC), and may confer resistance to prior endocrine therapy but retain sensitivity to neratinib. Neratinib is an oral, irreversible, pan-HER tyrosine kinase inhibitor with clinical activity either as a single agent or in combination with fulvestrant in HER2-mutated, HER2-non-amplified MBC. Genomic analyses suggest that acquired resistance to neratinib can occur via additional HER2 alterations, which may alter HER2-pathway signaling. We investigated whether dual HER2-targeted therapy could improve clinical benefit in a cohort of patients with HER2-mutant, HR+ MBC treated with neratin…
Abstract P1-19-08: Neratinib + trastuzumab + fulvestrant for HER2-mutant, hormone receptor-positive, metastatic breast cancer: Updated results from the phase 2 SUMMIT ‘basket’ trial
Abstract Background: HER2 mutations define a subset of metastatic breast cancers (MBCs) with a unique mechanism of oncogenic addiction to HER2 signaling. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has been shown to have encouraging clinical activity when combined with fulvestrant in HER2-mutant, hormone receptor-positive (HR+) MBC [Smyth et al. SABCS 2018]. Genomic analyses suggest that acquired resistance to neratinib may occur by the acquisition of additional HER2 alterations, which may amplify HER2 pathway signaling [Won et al. AACR 2019]. We therefore explored whether dual HER2-targeted therapy may improve clinical benefit in this setting. Here we describe initial res…
Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
Journal article TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ~480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10!-7), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10!-8) and BRCA1 mutation carrier (P = 1.1 × 10!-5) breast cancers and altered promot…