Lobular carcinoma in situ (LCIS) signifies an anomalous growth of undifferentiated, loosely organized, soft epithelial cells within the confines of the terminal duct lobular unit (TDLU) of the breast. At Protheragen, we focus on integrated preclinical therapeutics development for lobular carcinoma in situ (LCIS). Our services encompass a wide range of diagnostic and therapeutic approaches, tailored to meet the specific needs of our clients.
Overview of Lobular Carcinoma in Situ (LCIS)
Lobular carcinoma in situ (LCIS) is a type of in situ neoplasm which consists of abnormal cells growth within the terminal duct lobular unit (TDLU) of the breast. LCIS, is usually discovered during biopsies performed for other reasons, increases the likelihood of invasive carcinomas by approximately 7-10 times when compared to the general population. The diagnosis of LCIS encompasses both classic LCIS and atypical lobular hyperplasia (ALH), with the distinction being primarily quantitative and arbitrary. LCIS is often multicentric, bilateral, and clinically silent, making it challenging to detect without histopathological examination.
Fig.1 Spectrum of lobular neoplasia (LN). (Sokolova A.,
et al., 2021)
Pathogenesis of Lobular Carcinoma in Situ (LCIS)
The pathogenesis of LCIS is multi-faceted and includes molecular and genetic changes that upset normal cell adhesion and proliferation processes. Loss of E-cadherin expression, a cell adhesion molecule and a product of the CDH1 gene, is a central feature of LCIS. This loss enables greater invasive potential of lobular carcinoma. Genetic research have found recurrent deletions of 16q and 17p alongside the gains on 1q, markers which undergo neoplastic modification. In conjunction with this, there is also the alteration of the PI3K/AKT/mTOR estrogen receptor signaling pathways which contributes to the emergence of LCIS. All these factors result in abnormal proliferation which, in turn, increases the likelihood of progressing toward an invasive disease.
Diagnostics Development for Lobular Carcinoma in Situ (LCIS)
Histopathological Examination
LCIS diagnosis mostly utilizes histopathology of the breast tissue specimen acquired through a biopsy. Classic LCIS displays monomorphic, loosely cohesive cells that fill and expand at least 50\% of the acini of a TDLU. E-cadherin immunohistochemistry is done to distinguish between lobular and ductal neoplasia which in the case of lobular carcinoma in situ usually shows loss of staining or atypical membranous staining.
Molecular Profiling
The use of advanced molecular techniques, such as comparative genomic hybridization (CGH) and next-generation sequencing (NGS), is becoming more common for the identification of genetic changes in LCIS. These procedures assist in appreciating the risk of development of invasive carcinoma and further clarify the clonal nature of LCIS. For instance, detection of CDH1 mutations and loss of heterozygosity on 16q are fundamental in confirming the diagnosis and determining the molecular fundamental components of LCIS.
Therapeutics Development for Lobular Carcinoma in Situ (LCIS)
- Chemoprevention
The intention of these strategies is to lower the likelihood of invasive breast cancer in a person who has been diagnosed with LCIS. Some medications, for example, tamoxifen and aromatase inhibitors have been shown to effectively lower the chances of developing breast cancer in high-risk groups. These compounds interact with endocrine pathways, which in most cases are dysfunctional in LCIS.
- Targeted Therapies
Targeted strategies concentrate on particular molecular changes found in lobular carcinoma in situ (LCIS). For instance, therapies aimed at the PI3K/AKT/mTOR pathways are being developed because there are frequent gaps in this pathway in LCIS. Furthermore, agents directed at the E-cadherin succumbing are being examined because of the key role of E-cadherin loss in the LCIS pathogenesis.
Table 1. Therapeutics of Lobular Carcinoma in Situ (LCIS).
| Drug Name |
Target |
Description |
Stage |
| Tamoxifen |
Estrogen receptors |
A selective estrogen receptor modulator (SERM) that blocks estrogen receptors in breast cells, reducing the risk of estrogen-sensitive breast cancer. |
Approved |
| Raloxifene |
Estrogen receptors |
Another SERM, approved for postmenopausal women to reduce breast cancer risk and also used for osteoporosis prevention. |
Approved |
| Anastrozole |
Aromatase enzyme |
An aromatase inhibitor that reduces estrogen production in postmenopausal women, thereby lowering the risk of estrogen receptor-positive breast cancer. |
Approved |
| Exemestane |
Aromatase enzyme |
An aromatase inhibitor that decreases estrogen levels in the body, helping to prevent the development of breast cancer in high-risk postmenopausal women. |
Approved |
| Ruxolitinib |
Janus Kinase (JAK) signaling pathway |
Ruxolitinib is a JAK inhibitor that blocks the JAK-STAT signaling pathway, which is involved in the regulation of cell growth, differentiation, and immune response. |
Phase II (NCT02928978) |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen is dedicated to advancing the field of Lobular Carcinoma in Situ (LCIS) research through our comprehensive diagnostics and therapeutics development services. Our expertise, combined with our commitment to excellence, positions us as a leader in the industry, ready to support your research endeavors.
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
- Cdh1; Trp53 GEMMs
- Invasive Lobular Breast Cancer (ILC) PDXs
- Cdh1; Pten GEMMs
- SUM-44PE and MDA-MB-134-VI Xenografts
Protheragen's
preclinical research services for LCIS include in vitro and in vivo models to study the pathogenesis, progression, and potential therapeutic targets of LCIS. We utilize state-of-the-art technologies and methodologies to ensure the highest quality of research outcomes. If you are interested in our services, please feel free to
contact us.
References
- Sokolova, Anna, and Sunil R. Lakhani. "Lobular carcinoma in situ: diagnostic criteria and molecular correlates." Modern Pathology 34 (2021): 8-14.
- Wen, Hannah Y., and Edi Brogi. "Lobular carcinoma in situ." Surgical pathology clinics 11.1 (2018): 123-145.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
