Medullary Breast Carcinoma (MBC) is an uncommon and one of the specific subtypes of invasive breast cancer. It is characterized by distinctive histological and molecular features. Protheragen's diagnostics and therapeutics development services are distinguished by a very high level of scientific precision, innovation, and industry. Our company employs modern technologies and approaches that expedite the development processes without compromising quality.
Overview of Medullary Breast Carcinoma (MBC)
Medullary Breast Carcinoma (MBC) is a peculiar and rare sub-type of invasive breast cancer which accounts for less than 1% of all breast malignant tumors. Invasive MBC is marked by the presence of well-circumscribed tumor margins, syncytial growth of the tumor, prominent lymphoplasmacytic tumor stroma, and high-grade nuclei. Paradoxically, MBC has a more favorable outcome than other triple-negative breast cancers (TNBCs) despite its aggressive histological appearance, with some cohorts reporting greater than 80%-decade survival. It is believed that MBC's unique prognosis is due to its dense immune cell infiltration that may control metastatic spread. MBC is strongly linked to BRCA1 germline mutations and typically manifests as ER-negative, PR-negative, HER2-negative, which places it in the basal-like molecular subtype.
Fig.1 Photomicrograph shows syncytial growth pattern exhibited by a medullary breast carcinoma, with distinct intercellular borders (H&E, ×40). (Ju H.,
et al., 2023)
Pathogenesis of Medullary Breast Carcinoma (MBC)
The pathogenesis of MBC is driven by a combination of genetic, immunological, and microenvironmental factors:
- BRCA1 dysfunction: About 60-80% of BRCA1-linked breast cancers exhibit medullary-like features, which connect MBC to malfunctioning DNA repair systems.
- TP53 mutations: Found in over 80% of MBC cases, this contributes to the high-grade morphology and genomic instability.
- Immune microenvironment: The presence of dense lymphocytic infiltrates (CD8+ T cells and B cells) is associated with a better prognosis, pointing toward immune-related mechanisms of tumor control.
- Basal-like phenotype: Overexpression of basal markers, including EGFR, CK14, and 34BE12, along with the absence of hormone receptors delineate its aggressive, although paradoxically indolent behavior.
- Epigenetic alterations: Further tumor progression may be driven by hypermethylation of tumor suppressor genes such as RASSF1A.
Diagnostics Development for Medullary Breast Carcinoma (MBC)
Histopathological Diagnosis
A specific set of criteria must be met for the histopathological diagnosis of MBC which includes syncytial growth pattern, complete microscopic circumscription, diffuse mononuclear stromal infiltrate, and absence of microglandular features. These criteria are evaluated under light microscopy and are vital in the differentiation of MBC from other subtypes of breast cancer. An example of this is identifying a circumscribed tumor containing syncytial sheets of pleomorphic cells with dense lymphoplasmacytic infiltrate which suggests MBC.
Immunohistochemical Diagnosis
In the case of Medullary Breast Carcinoma (MBC), confirming the diagnosis and detailing the molecular profile requires immunohistochemical analysis. MBCs usually display triple-negative phenotype, wherein ER, PR, and HER2 are not expressed. In addition, they are frequently positive for basal markers including cytokeratin 14 (CK14), epidermal growth factor receptor (EGFR), and 34BE12. These markers assist in defining the basal-like phenotype of MBCs and differentiating them from other triple-negative Medullary Breast Carcinomas (MBCs).
Molecular Diagnostics
Specific genetic mutations and alterations in Metastatic Breast Cancers (MBCs) are being identified with greater precision through molecular diagnostics like next-generation sequencing (NGS) and genomic profiling. These methods are capable of identifying mutational changes such as BRCA1 and TP53 mutations which play an important role in the oncogenic evolution of Medullary Breast Carcinoma (MBC). Additionally, molecular diagnostics have a role in determining therapy-responsive predictive factors and potential therapeutic targets.
Therapeutics Development for Medullary Breast Carcinoma (MBC)
Chemotherapy
Although MBCs are triple negative, adjuvant chemotherapy is applied in some cases, especially with lymph node involvement. Commonly, chemotherapy regimens consist of anthracycline, taxane, and other cytotoxic agents. For instance, some studies confirm that adjuvant chemotherapy improves disease-free survival in cases with node-positive MBC.
Targeted Therapies
Targeted therapies are still developing in the scope of research regarding MBC. Because of the overexpression of EGFR in some MBCs, EGFR inhibitors are being investigated as possible therapeutic modalities. Also, MBCs bearing BRCA1 mutations are being treated with PARP inhibitors and studied further. For instance, some clinical trials focus on evaluating the effectiveness of PARP inhibitors for cases with MBC and a BRCA1 mutation.
Immunotherapy
Immunotherapy is another highly promising branch of research in regard to MBC. The rich lymphoplasmacytic infiltrate seen in MBCs indicates that at least some immune checkpoint targets and other immunomodulatory therapies will be active. For instance, researchers are investigating the application of PD-1 and PD-L1 blockers in MBCs to bolster the immune system’s antitumor activity.
Our Services
The diagnostics and therapeutics development services of Protheragen for MBC have notable advantages. Our comprehensive approach ensures that clients receive a detailed and accurate characterization of MBC tumors, enabling the development of targeted therapies and customized therapeutic strategies.
Diagnostics Development
- Karyotype Analysis Service
- Omics Analysis Service
- Biomarker Development Service
- Artificial Intelligence Service
- Customized Diagnostics Development
Therapeutic Development
- Anticancer Peptide
- Gene Therapy
- Immunotherapy
- Monoclonal Antibody
- Phytotherapy
- Small Molecule Drug
- Therapeutic Cancer Vaccine
Disease Models
- 2D Monolayer Cell Culture
- 3D Spheroid Culture
- BRCA1 Mutation Mouse Models
- TP53 Mutation Mouse Models
- Large Animal Models
Protheragen stands out for offering tailor-made services bespoke to the requirements of different projects. Understanding how MBC research can be uniquely challenging, Protheragen works closely with the clients to formulate and implement studies that meet their coordinated goals. These include, but are not limited to, custom assay development, model generation, and data analysis. If you are interested in our services, please feel free to
contact us.
References
- Ju, Hong, et al. "A rare case of invasive cribriform carcinoma in male breast." The American Journal of Case Reports 24 (2023): e938939-1.
- Branca, Giovanni, et al. "An updated review of cribriform carcinomas with emphasis on histopathological diagnosis and prognostic significance." Oncology reviews 11.1 (2017): 317.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
