Overview of Test
Invasive breast cancers can be classified by gene expression into at least four major biologic “intrinsic” subtypes referred to as Luminal A, Luminal B, HER2-enriched, and Basal-like1. These subtypes have been reproducibly identified in the research setting by microarray1,2,3,4 and RT-qPCR1,5,6. In 2009, Parker, et al. proposed a 50-gene set (PAM50) for standardizing subtype classification1. The PAM50 Breast Cancer Intrinsic Classifier is the clinical manifestation of this gene set using an RT-qPCR assay that has been validated on formalin-fixed, paraffin-embedded tissues. Multivariable analyses using the PAM50 subtypes and other clinical data (e.g., node status, grade, ER-status) show that the PAM50 is an independent predictor of survival in breast cancer1,6.
Standard methods for diagnosing and treating breast cancer include anatomic staging, histological assessment, and immunohistochemical testing for ER, PR, and HER2/neu protein expression. The PAM50 test provides additional information about the tumor biology and quantitative data on biomarkers already used for treatment decisions. Along with a categorical classification of breast cancer subtype, the clinical PAM50 test also provides quantitative values for proliferation, luminal gene expression, ESR1, PGR, and ERBB2. The genes used for subtyping, individual gene scores, and meta-gene scores are provided below:
| ACTB | ACTR3B | ANLN | BAG1 | BCL2 |
| BIRC5 | BLVRA | CCNB1 | CCNE1 | CDC20 |
| CDC6 | CDCA1 | CDH3 | CENPF | CEP55 |
| CXXC5 | EGFR | ERBB2 | ESR1 | EXO1 |
| FGFR4 | FOXA1 | FOXC1 | GPR160 | GRB7 |
| KIF2C | KNTC2 | KRT14 | KRT17 | KRT5 |
| MAPT | MDM2 | MELK | MIA | MKI67 |
| MLPH | MMP11 | MRPL19 | MYBL2 | MYC |
| NAT1 | ORC6L | PGR | PHGDH | PSMC4 |
| PTTG1 | RPLP0 | RRM2 | SF3A1 | SFRP1 |
| SLC39A6 | TMEM45B | TYMS | UBE2C | UBE2T |
| Control Gene | Proliferation Gene | Luminal Gene |
|---|
References
1. Parker JS, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 2009;27(8):1160–7.
2. Perou CM, et al. Molecular portraits of human breast tumours. Nature 2000;406:747–52.
3. Sorlie T, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003;100:8418–23.
4. Mullins M, et al. Agreement in breast cancer classification between microarray and quantitative reverse transcription PCR from fresh-frozen and formalin-fixed, paraffin-embedded tissues. Clin Chem 2007;53:1273–9.
5. Hu Z, et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 2006;7:96.
6. Nielsen TO, et al. A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor positive breast cancer. Clin Cancer Res 2010;16(21):5222–5232.