Multigene Tests Compared for Breast Cancer Prognosis

Several commercial assays are being introduced to assign clinical subtype or predict risk of recurrence for breast cancer of which there are at least four different subtypes with clinical relevance.

Scientists at Mater Misericordiae University Hospital (Dublin, Ireland) extracted ribonucleic acid (RNA) from 119 formalin-fixed, paraffin-embedded tissue blocks from breast cancer patients who have been classified as being at clinically intermediate risk for recurrence based on several criteria: median tumor size 1.5 cm, all estrogen receptor (ER)-positive, Human Epidermal growth factor Receptor 2 (HER2) -negative, lymph-node negative and most of them were classified as grade II. Working with colleagues in the USA, the scientists performed the PAM50 Breast Cancer Intrinsic Classifier Reverse Transcription/Quantitative Polymerase Chain Reaction and compared it to the OncotypeDX recurrence score (RS) assay.

The results showed that all patients with high RS according to the OncotypeDX were classified as 'luminal B' or 'basal-like' by the PAM50 classifier, whereas 83%, the majority of low RS cases were "luminal A" type. Half of the Intermediate RS cancers were recategorized as low risk 'luminal A' cancers by the PAM50. All 'luminal A' cancers are either low (70%) or intermediate (30%) risk by RS, whereas 'luminal B' cancers are comprised of a mixed risk group by RS including 33% that are high risk by OncotypeDX. These results indicate that there is a reasonably good agreement between the two methods for high and low prognostic risk assignment. According to the authors of the study, intermediate risk groups by one assay often include cases with discordant risk prediction by the other method. When discordant risk results are obtained it is currently unknown which assay will predict outcome more accurately.

The OncotypeDX test (Genomic Health; Redwood City, CA, USA) is intended for use in patients with hormone receptor-positive, lymph node-negative breast cancer to identify women at low risk of breast cancer recurrence who can safely avoid chemotherapy. It measures the activity of 21 genes and generates a recurrence score (RS) which categorizes patients into low, intermediate or high risk groups depending on the risk of distant recurrence. The PAM50 breast cancer intrinsic classifier, (ARUP Laboratories; Salt Lake City, UT, USA) measures the expression of 50 genes and stratifies breast cancers into five sub-types; luminal A, luminal B, basal-like, Her2-enriched and normal-like, so the target population is not just patients with ER-positive breast cancers. This test is currently undergoing clinical validation. The study was presented at the Improving Care and Knowledge Through Translational Research (IMPAKT) Breast Cancer Conference, 5-7 May, 2011, held in Brussels, Belgium.

Related Links:
Mater Misericordiae University Hospital
Genomic Health
ARUP Laboratories