Breast carcinoma is a diverse disease with varying morphological, phenotypical, and biological characteristics, which impact disease progression and therapeutic responsiveness. Molecular classification has greatly impacted clinical management and prediction of clinical outcomes, but it is not perfect. Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer (IBC) and is associated with 45-78% of all invasive breast cancers. However, not all IBC are preceded by DCIS, even though carcinogenesis starts from a single ductal epithelial cell.
My paper in 2017 dealt with multifocal tumors which can be of different origins despite being closely located to each other, and phenotypes of multifocal breast cancer are heterogeneous. Further study using whole-exome sequencing revealed that a DCIS lesion in the breast of one patient displayed a greater amount of genetic aberration than the accompanying IBC, which can imply that a subset of DCIS was as advanced or more advanced than the synchronous IBC. We demonstrated genetic intra-tumoral heterogeneity in DCIS lesions coexisting with IBC. My colleague and I recently demonstrated that the Luminal B type is the most common of the heterogeneous phenotypes through immunohistochemical analysis.
Many benign breast diseases, such as ductal hyperplasia, fibroadenoma, papilloma, and lobular hyperplasia, are associated with breast cancer. Currently, we use a widely accepted classification system based on pathological and molecular phenotype. However, we are exploring the potential of a more meticulous classification of breast cancer based on the presence or absence of DCIS and/or depending on the type of benign breast disease.
For this study, in 2019, we roughly mapped 500 pathological samples of breast cancer patients at Korea University Guro Hospital. Pathological evaluations were carefully conducted and analyzed not only for breast cancer but also for accompanying DCIS and benign breast disease. This new classification could provide valuable insight into the carcinogenesis of breast cancer as well as set a new paradigm for screening, diagnosing, and treating patients.