BluePrint™ Provides Deeper Insights into Your Patient's Tumor Biology

BluePrint provides physicians with more information about their patient’s unique tumor biology.  Following risk assessment with a MammaPrint^® 'low risk' or 'high risk' result, and when used in conjunction with other clinical risk factors, BluePrint will allow physicians to more accurately tailor treatment decision-making for each breast cancer patient.

Result Description of Basal-type

Basal-type breast cancers are characterized by gene expression of the basal-myoepithelial cell origin. The Basal-type cancers are typically triple-negative for ER, PR and HER2/neu (basal-like) with a specific gene expression profile. Hormone therapy and anti-HER2 therapies, such as trastuzumab and lapatinib, are not believed  to be effective against these cancers, although chemotherapy is thought to be helpful.  A Basal-type molecular subtyping result means that the tumor most closely resembles the Basal-type intrinsic subtype.

Result Description of Luminal-type

Luminal-type breast cancers are characterized by gene expression of luminal epithelial cells that line the breast ducts and glands. The Luminal-type cancers are typically hormone receptor positive tumors and therefore responsive to hormonal therapy. A Luminal-type molecular subtyping result means that the tumor most closely resembles the Luminal-type intrinsic subtype. Patients classified as MammaPrint 70-gene signature 'low risk' and Luminal-type can be expected to have a clinical course similar to luminal A, usually treated with hormonal therapy. Patients classified as MammaPrint 'high risk' and Luminal-type can be expected to have a clinical course similar to luminal B patients who usually benefit from more aggressive treatment which may include chemotherapy.

Result Description of ERBB2-type

The ERBB2-type breast cancers are characterized by amplification or over-expression of the HER2 locus. The ERBB2-type cancers are typically HER2-positive tumors (HER2/neu positive). ERRB2-type cancers tend to grow more quickly and may recur, although they can often be treated with targeted therapies such as trastuzumab and lapatinib. An ERBB2-type molecular subtyping result means that the tumor most closely resembles the ERBB2-type intrinsic subtype.

Assay Description

Gene expression analysis has confirmed the heterogeneity of breast cancer, revealing it to be a disease with intrinsic subgroups that can be uncovered by genomic profiling.⁽¹⁾ The BluePrint molecular subtyping profile was designed to distinguish the Basal-type, Luminal-type and ERBB2-type (HER2/neu positive) intrinsic subgroups of tumors.⁽²⁾ The BluePrint signature determines the RNA levels of 80 genes that best discriminate among these three distinctive subtypes. Tumors from a cohort of 295 patients were used for the development of gene expression profiles specific for the Basal-type, Luminal-type and ERBB2-type breast cancers. Using state-of-the-art bioinformatics tools, Agendia identified genes whose expression ratios best discriminate between the three subgroups. Subtype specific gene expression profiles were identified in a 3-fold cross-validation procedure. Optimal classification of the training samples in the corresponding Basal-type, Luminal-type and ERBB2-type subgroups was reached with a set of 80 genes. Next, a nearest-centroid classification procedure utilizing the 80-gene profile was developed that most accurately classified the breast cancer molecular subtypes on all samples. The BluePrint molecular subtyping profile was subsequently validated on 374 independent samples and demonstrated high concordance with the subgroups (excluding normal-like) described by Perou et al.^(1,2)