Abstract P4-11-08: Pathological assessment of discordant cases for molecular (BluePrint and MammaPrint) vs clinical subtypes for breast cancer, among 6,694 patients from the EORTC 10041/BIG 3-04 (MINDACT) trial

Background: Biology has become the main driver of breast cancer therapy. Intrinsic biological subtypes by gene expression profiling have been identified. Pathology can be used to define surrogates of these subtypes but these are not always concordant, which may lead to different treatment plans. We investigated the concordance between BluePrint and MammaPrint (microarray-based) breast cancer subtypes and pathological surrogates (based on ER, PR, HER2 & Ki67). Methods: Using available data (centrally assessed pathology and genomics) from the MINDACT pilot phase [Rutgers et al. EJC 2011] 621 tumors were analyzed. Patients were classified according to 4-category based pathology (ER, PR, HER2 and Ki67); additionally, classification was performed adhering to the recent St. Gallen recommendations [Goldhirsch et al. 2011], which recognizes an additional category (Luminal B HER2+). Based on BluePrint and MammaPrint 4 subtypes are formed: Luminal A (Luminal-type/MammaPrint Low Risk); Luminal B (Luminal-type/MammaPrint High Risk); HER2-type; and Basal-type. This study is an analysis of discordant patient groups (i.e. clinical HER2+/BluePrint Luminal-type; clinical Hormone Receptor (HR)-positive/BluePrint Basal-type) providing comparison of centrally assessed tumor heterogeneity as well as comparison of quantified ER, PR and HER2 results. Results: Ki67 is often used as biomarker to distinguish Luminal A from Luminal B subgroups. The concordance between MammaPrint and centrally assessed Ki67 in Luminal-type patients is 71%, with a κ score of 0.35 (95% CI 0.26–0.45) indicating that Ki67 and MammaPrint cannot reliably substitute for each other. There is a relatively large group of clinical HER2+ cases that are BluePrint Luminal-type (29 out of 76; 38%) indicating that tumor expression of the Luminal profile is dominant compared with expression of the HER2 profile. These patients have high IHC ER results and fall into the group that St Gallen separately defines as Luminal B HER2-type. These patients may have lower response to trastuzumab [von Minckwitz et al. JCO 2012]. 12 out of 76 BluePrint Basal-type patients are clinical HR+. These patients have low centrally assessed IHC ER and PR expression (≥1% and Conclusions: Marked differences are observed between BluePrint and MammaPrint (microarray based) breast cancer subtypes and centrally re-assessed pathological surrogates (based on ER, PR, HER2 & Ki67). The greatest discordance is seen in the sub-stratification of Luminal patients, and in the HR+/HER2+ patients. The observed subtype discrepancies may have an important impact on treatment decision making. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-05-02.