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Ref Type Journal Article
PMID (26503204)
Authors Hortobagyi GN, Chen D, Piccart M, Rugo HS, Burris HA, Pritchard KI, Campone M, Noguchi S, Perez AT, Deleu I, Shtivelband M, Masuda N, Dakhil S, Anderson I, Robinson DM, He W, Garg A, McDonald ER, Bitter H, Huang A, Taran T, Bachelot T, Lebrun F, Lebwohl D, Baselga J
Title Correlative Analysis of Genetic Alterations and Everolimus Benefit in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From BOLERO-2.
Journal Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Vol 34
Issue 5
Date 2016 Feb 10
URL
Abstract Text To explore the genetic landscape of tumors from patients enrolled on the BOLERO-2 trial to identify potential correlations between genetic alterations and efficacy of everolimus treatment. The BOLERO-2 trial has previously demonstrated that the addition of everolimus to exemestane prolonged progression-free survival by more than twofold in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer previously treated with nonsteroidal aromatase inhibitors.Next-generation sequencing was used to analyze genetic status of cancer-related genes in 302 archival tumor specimens from patients representative of the BOLERO-2 study population. Correlations between the most common somatic alterations and degree of chromosomal instability, and treatment effect of everolimus were investigated.Progression-free survival benefit with everolimus was maintained regardless of alteration status of PIK3CA, FGFR1, and CCND1 or the pathways of which they are components. However, quantitative differences in everolimus benefit were observed between patient subgroups defined by the exon-specific mutations in PIK3CA (exon 20 v 9) or by different degrees of chromosomal instability in the tumor tissues.The data from this exploratory analysis suggest that the efficacy of everolimus was largely independent of the most commonly altered genes or pathways in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. The potential impact of chromosomal instabilities and low-frequency genetic alterations on everolimus efficacy warrants further investigation.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PIK3CA exon21 Her2-receptor negative breast cancer no benefit Everolimus Phase III Actionable In a retrospective analysis of a Phase III trial (BOLERO-2), Afinitor (everolimus) demonstrated greater benefit on progression-free survival in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring PIK3CA exon 10 (reported as exon 9) mutations (HR=0.26) compared to patients harboring PIK3CA exon 21 (reported as exon 20) mutations (HR=0.56) (PMID: 26503204; NCT00863655). 26503204
PIK3CA exon10 Her2-receptor negative breast cancer predicted - sensitive Everolimus Phase III Actionable In a retrospective analysis of a Phase III trial (BOLERO-2), Afinitor (everolimus) demonstrated greater benefit on progression-free survival in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring PIK3CA exon 10 (reported as exon 9) mutations (HR=0.26) compared to patients harboring PIK3CA exon 21 (reported as exon 20) mutations (HR=0.56) (PMID: 26503204; NCT00863655). 26503204
PIK3CA mutant Her2-receptor negative breast cancer no benefit Everolimus Phase III Actionable In a retrospective analysis of a Phase III trial (BOLERO-2), the presence of PIK3CA mutations did not significantly affect the efficacy of Afinitor (everolimus) in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer, with a HR for progression-free survival of 0.37 in PIK3CA wild-type group and a HR of 0.51 (p=0.35) in patients with PIK3CA mutations (PMID: 26503204; NCT00863655). 26503204