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04.05.2018 | Preclinical study | Ausgabe 1/2018

Breast Cancer Research and Treatment 1/2018

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

Zeitschrift:
Breast Cancer Research and Treatment > Ausgabe 1/2018
Autoren:
Ryo Tsunashima, Yasuto Naoi, Kenzo Shimazu, Naofumi Kagara, Masashi Shimoda, Tomonori Tanei, Tomohiro Miyake, Seung Jin Kim, Shinzaburo Noguchi
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10549-018-4812-0) contains supplementary material, which is available to authorized users.

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.

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Zusatzmaterial
Supplementary Fig. 1. Prediction of prognosis by 42GC for recurrent breast cancer patients. Distant metastasis-free survival (DMFS) rates were compared between the late recurrence-like (LR) and the non-late recurrence-like (NLR) groups in the training set (a) and the validation set (b). Supplementary material 1 (PPTX 69 KB)
10549_2018_4812_MOESM1_ESM.pptx
Supplementary material 2 (DOC 87 KB)
10549_2018_4812_MOESM2_ESM.doc
Literatur
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