Skip to main content
eScholarship
Open Access Publications from the University of California

UC San Diego

UC San Diego Previously Published Works bannerUC San Diego

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

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

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View