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Open Access 01-01-2020 | Breast Cancer | Epidemiology

Research-based PAM50 signature and long-term breast cancer survival

Authors: Minya Pu, Karen Messer, Sherri R. Davies, Tammi L. Vickery, Emily Pittman, Barbara A. Parker, Matthew J. Ellis, Shirley W. Flatt, Catherine R. Marinac, Sandahl H. Nelson, Elaine R. Mardis, John P. Pierce, Loki Natarajan

Published in: Breast Cancer Research and Treatment | Issue 1/2020

Abstract

Purpose

Multi-gene signatures provide biological insight and risk stratification in breast cancer. Intrinsic molecular subtypes defined by mRNA expression of 50 genes (PAM50) are prognostic in hormone-receptor positive postmenopausal breast cancer. Yet, for 25–40% in the PAM50 intermediate risk group, long-term risk remains uncertain. Our study aimed to (i) test the long-term prognostic value of the PAM50 signature in pre- and post-menopausal breast cancer; (ii) investigate if the PAM50 model could be improved by addition of other mRNAs implicated in oncogenesis.

Methods

We used archived FFPE samples from 1723 breast cancer survivors; high quality reads were obtained on 1253 samples. Transcript expression was quantified using a custom codeset with probes for > 100 targets. Cox models assessed gene signatures for breast cancer relapse and survival.

Results

Over 15 + years of follow-up, PAM50 subtypes were (P < 0.01) associated with breast cancer outcomes after accounting for tumor stage, grade and age at diagnosis. Results did not differ by menopausal status at diagnosis. Women with Luminal B (versus Luminal A) subtype had a > 60% higher hazard. Addition of a 13-gene hypoxia signature improved prognostication with > 40% higher hazard in the highest vs lowest hypoxia tertiles.

Conclusions

PAM50 intrinsic subtypes were independently prognostic for long-term breast cancer survival, irrespective of menopausal status. Addition of hypoxia signatures improved risk prediction. If replicated, incorporating the 13-gene hypoxia signature into the existing PAM50 risk assessment tool, may refine risk stratification and further clarify treatment for breast cancer.

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Title: Research-based PAM50 signature and long-term breast cancer survival
Authors: Minya Pu
Karen Messer
Sherri R. Davies
Tammi L. Vickery
Emily Pittman
Barbara A. Parker
Matthew J. Ellis
Shirley W. Flatt
Catherine R. Marinac
Sandahl H. Nelson
Elaine R. Mardis
John P. Pierce
Loki Natarajan
Publication date: 01-01-2020
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 1/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05446-y

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