Genomic testing is becoming part of the standard-of-care for diagnosis of breast cancer. While molecular classification of breast tumors is not widely used in the clinic, there is wider acceptance of prognostic genomic assays that predict likelihood of tumor recurrence. These tests can spare women who are at low risk of recurrence from unnecessary chemotherapy.

Breast cancer affects 1 in 8 women in the United States, with a survival rate ranging between 23-98%. In the clinical lab, breast cancer subtypes are identified using histology and immunohistochemistry for ESR1, PGR, and Her2/Neu. In Situ Hybridization (FISH, CISH, or DISH) is also used for evaluation of Her2/Neu amplification. Staining for cell-specific markers also assists the characterization of breast malignancies. The majority of breast tumors are ESR1 positive (80%). All ESR1 positive patients receive endocrine therapy, although 30-40% experience recurrence within 10 years.

It has been known for a while that there are four main “intrinsic” molecular subtypes of breast cancer, Luminal A, Luminal B, basal-like, and ERBB2, with significant heterogeneity within each class. Such information has not been used in the clinical evaluation of breast cancer patients because it is more costly than current methods and has yet to demonstrate efficacy in improving therapeutic outcome. However, there are yet many more types of breast cancer, and there is a need for clinical genomic tests that would accurately identify these classes and link them to proper selection of therapy. This has been our motivation to develop a sensitive, specific, and quantitative molecular diagnostic test for breast cancer.

After many years of research, we have developed a gene expression-based test for molecular classification of breast cancer tumors and specifically to predict response to Tamoxifen therapy. The Falcon Breast Cancer Test currently identifies 8 classes of breast cancer with high specificity and sensitivity, namely the ESR1-negative, Basal-like, ERBB2, and Normal-like, and the ESR1-positive, Lobular, L1, L2, L3, and L4 tumors.

In our validation studies, we observed that lobular tumors usually express ESR1, but have very low levels of E-Cadherin (CDH1). L1 samples, also known in the literature as Luminal-B, expressed high levels of proliferation genes and showed the highest likelihood of recurrence among untreated patients, but responded well to Tamoxifen treatment. However, the likelihood of recurrence after Tamoxifen for these patients is similar to other untreated Luminal groups (L3-L4). While L3 and L4 patients showed statistically significant increase in survival after Tamoxifen, L2 patients did not. By further classifying ESR1-positive tumors, we were able to identify key genes that are associated with survival in each one of these groups.

In summary, the Falcon Breast Cancer Test provides comprehensive classification of breast cancer. Consequently, if integrated into the standard of care, it has the potential to identify patients that would not respond to Tamoxifen therapy at an early stage. Furthermore, the test can also reveal class-specific gene targets for therapy. These targets could then be validated using our 3D functional genomic test, the Falcon Cancer BioChip. This will lead to the development of more effective and targeted therapy for each type of breast cancer.