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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2018

01-08-2018 | Preclinical study

Construction of a novel multi-gene assay (42-gene classifier) for prediction of late recurrence in ER-positive breast cancer patients

Authors: Ryo Tsunashima, Yasuto Naoi, Kenzo Shimazu, Naofumi Kagara, Masashi Shimoda, Tomonori Tanei, Tomohiro Miyake, Seung Jin Kim, Shinzaburo Noguchi

Published in: Breast Cancer Research and Treatment | Issue 1/2018

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Abstract

Purpose

Prediction models for late (> 5 years) recurrence in ER-positive breast cancer need to be developed for the accurate selection of patients for extended hormonal therapy. We attempted to develop such a prediction model focusing on the differences in gene expression between breast cancers with early and late recurrence.

Methods

For the training set, 779 ER-positive breast cancers treated with tamoxifen alone for 5 years were selected from the databases (GSE6532, GSE12093, GSE17705, and GSE26971). For the validation set, 221 ER-positive breast cancers treated with adjuvant hormonal therapy for 5 years with or without chemotherapy at our hospital were included. Gene expression was assayed by DNA microarray analysis (Affymetrix U133 plus 2.0).

Results

With the 42 genes differentially expressed in early and late recurrence breast cancers in the training set, a prediction model (42GC) for late recurrence was constructed. The patients classified by 42GC into the late recurrence-like group showed a significantly (P = 0.006) higher late recurrence rate as expected but a significantly (P = 1.62 × E−13) lower rate for early recurrence than non-late recurrence-like group. These observations were confirmed for the validation set, i.e., P = 0.020 for late recurrence and P = 5.70 × E−5 for early recurrence.

Conclusion

We developed a unique prediction model (42GC) for late recurrence by focusing on the biological differences between breast cancers with early and late recurrence. Interestingly, patients in the late recurrence-like group by 42GC were at low risk for early recurrence.
Appendix
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Metadata
Title
Construction of a novel multi-gene assay (42-gene classifier) for prediction of late recurrence in ER-positive breast cancer patients
Authors
Ryo Tsunashima
Yasuto Naoi
Kenzo Shimazu
Naofumi Kagara
Masashi Shimoda
Tomonori Tanei
Tomohiro Miyake
Seung Jin Kim
Shinzaburo Noguchi
Publication date
01-08-2018
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-018-4812-0

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