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

Gabriel N. Hortobagyi, David Chen, Martine Piccart, Hope S. Rugo, Howard A. Burris, Kathleen I. Pritchard, Mario Campone, Shinzaburo Noguchi, Alejandra Perez, Ines Deleu, Mikhail Shtivelband, Norikazu Masuda, Shaker Dakhil, Ian Anderson, Douglas M. Robinson, Wei He, Abhishek Garg, E. Robert McDonald, Hans Bitter, Alan HuangTetiana Taran, Thomas Bachelot, Fabienne Lebrun, David Lebwohl, José Baselga

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Purpose: 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. Patients and Methods: 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. Results: 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 exonspecificmutations in PIK3CA (exon 20 v 9) or by different degrees of chromosomal instability in the tumor tissues. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)419-426
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number5
DOIs
StatePublished - Feb 10 2016
Externally publishedYes

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Hormones
Breast Neoplasms
Chromosomal Instability
exemestane
Disease-Free Survival
Patient Advocacy
Neoplasms
Aromatase Inhibitors
Neoplasm Genes
Everolimus
human ERBB2 protein
Exons
Population
Genes
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Hortobagyi, Gabriel N.; Chen, David; Piccart, Martine; Rugo, Hope S.; Burris, Howard A.; Pritchard, Kathleen I.; Campone, Mario; Noguchi, Shinzaburo; Perez, Alejandra; Deleu, Ines; Shtivelband, Mikhail; Masuda, Norikazu; Dakhil, Shaker; Anderson, Ian; Robinson, Douglas M.; He, Wei; Garg, Abhishek; McDonald, E. Robert; Bitter, Hans; Huang, Alan; Taran, Tetiana; Bachelot, Thomas; Lebrun, Fabienne; Lebwohl, David; Baselga, José.

In: Journal of Clinical Oncology, Vol. 34, No. 5, 10.02.2016, p. 419-426.

Research output: Contribution to journalArticle

Hortobagyi, GN, Chen, D, Piccart, M, Rugo, HS, Burris, HA, Pritchard, KI, Campone, M, Noguchi, S, Perez, A, 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 2016, '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 of Clinical Oncology, vol. 34, no. 5, pp. 419-426. https://doi.org/10.1200/JCO.2014.60.1971
Hortobagyi, Gabriel N. ; Chen, David ; Piccart, Martine ; Rugo, Hope S. ; Burris, Howard A. ; Pritchard, Kathleen I. ; Campone, Mario ; Noguchi, Shinzaburo ; Perez, Alejandra ; Deleu, Ines ; Shtivelband, Mikhail ; Masuda, Norikazu ; Dakhil, Shaker ; Anderson, Ian ; Robinson, Douglas M. ; He, Wei ; Garg, Abhishek ; McDonald, E. Robert ; Bitter, Hans ; Huang, Alan ; Taran, Tetiana ; Bachelot, Thomas ; Lebrun, Fabienne ; Lebwohl, David ; Baselga, José. / 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. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 5. pp. 419-426.
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abstract = "Purpose: 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. Patients and Methods: 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. Results: 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 exonspecificmutations in PIK3CA (exon 20 v 9) or by different degrees of chromosomal instability in the tumor tissues. Conclusion: 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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AU - Hortobagyi, Gabriel N.

AU - Chen, David

AU - Piccart, Martine

AU - Rugo, Hope S.

AU - Burris, Howard A.

AU - Pritchard, Kathleen I.

AU - Campone, Mario

AU - Noguchi, Shinzaburo

AU - Perez, Alejandra

AU - Deleu, Ines

AU - Shtivelband, Mikhail

AU - Masuda, Norikazu

AU - Dakhil, Shaker

AU - Anderson, Ian

AU - Robinson, Douglas M.

AU - He, Wei

AU - Garg, Abhishek

AU - McDonald, E. Robert

AU - Bitter, Hans

AU - Huang, Alan

AU - Taran, Tetiana

AU - Bachelot, Thomas

AU - Lebrun, Fabienne

AU - Lebwohl, David

AU - Baselga, José

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N2 - Purpose: 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. Patients and Methods: 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. Results: 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 exonspecificmutations in PIK3CA (exon 20 v 9) or by different degrees of chromosomal instability in the tumor tissues. Conclusion: 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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