Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer

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Buus, RichardInstitute of Cancer Research London,Royal Marsden Hospital, London (author)

Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer

Article/chapterEnglish2018

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2018-09-04
Springer Science and Business Media LLC,2018

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LIBRIS-ID:oai:lup.lub.lu.se:1508ae8f-d83d-4ce1-9282-045b3c37faf0
https://lup.lub.lu.se/record/1508ae8f-d83d-4ce1-9282-045b3c37faf0URI
https://doi.org/10.1186/s13058-018-1040-9DOI

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Language:English
Summary in:English

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Background: Several prognostic signatures for early oestrogen receptor-positive (ER+) breast cancer have been established with a 10-year follow-up. We tested the hypothesis that signatures optimised for 0-5-year and 5-10-year follow-up separately are more prognostic than a single signature optimised for 10 years. Methods: Genes previously identified as prognostic or associated with endocrine resistance were tested in publicly available microarray data set using Cox regression of 747 ER+/HER2- samples from post-menopausal patients treated with 5 years of endocrine therapy. RNA expression of the selected genes was assayed in primary ER+/HER2- tumours from 948 post-menopausal patients treated with 5 years of anastrozole or tamoxifen in the TransATAC cohort. Prognostic signatures for 0-10, 0-5 and 5-10 years were derived using a penalised Cox regression (elastic net). Signature comparison was performed with likelihood ratio statistics. Validation was done by a case-control (POLAR) study in 422 samples derived from a cohort of 1449. Results: Ninety-three genes were selected by the modelling of microarray data; 63 of these were significantly prognostic in TransATAC, most similarly across each time period. Contrary to our hypothesis, the derived early and late signatures were not significantly more prognostic than the 18-gene 10-year signature. The 18-gene 10-year signature was internally validated in the TransATAC validation set, showing prognostic information similar to that of Oncotype DX Recurrence Score, PAM50 risk of recurrence score, Breast Cancer Index and IHC4 (score based on four IHC markers), as well as in the external POLAR case-control set. Conclusions: The derived 10-year signature predicts risk of metastasis in patients with ER+/HER2- breast cancer similar to commercial signatures. The hypothesis that early and late prognostic signatures are significantly more informative than a single signature was rejected.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
Biomarkers
Breast cancer
Late recurrence
Oestrogen receptor
Prognostic tests

Added entries (persons, corporate bodies, meetings, titles ...)

Yeo, BelindaAustin Health,Olivia Newton-John Cancer Research Institute (author)
Brentnall, Adam R.Queen Mary University (author)
Klintman, MarieLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-mkt (author)
Cheang, Maggie Chon U.Institute of Cancer Research London (author)
Khabra, KomelRoyal Marsden Hospital, London (author)
Sestak, IvanaQueen Mary University (author)
Gao, QiongInstitute of Cancer Research London (author)
Cuzick, JackQueen Mary University (author)
Dowsett, MitchInstitute of Cancer Research London,Royal Marsden Hospital, London (author)
Institute of Cancer Research LondonRoyal Marsden Hospital, London (creator_code:org_t)

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In:Breast Cancer Research: Springer Science and Business Media LLC20:11465-54111465-542X

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By the author/editor: Buus, Richard; Yeo, Belinda; Brentnall, Adam ...; Klintman, Marie; Cheang, Maggie C ...; Khabra, Komel; show more...; Sestak, Ivana; Gao, Qiong; Cuzick, Jack; Dowsett, Mitch; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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