Li-Fraumeni Syndrome (LFS) is one of the most difficult conditions in oncology and one of the few hereditary syndromes that has an incredibly high lifetime risk of multiple cancers, including highly aggressive early-onset breast cancer. Protheragen provides full services concerning the development of diagnostics and therapeutics for breast cancer associated with LFS.
Overview of Li-Fraumeni Syndrome (LFS)-associated Breast Cancer
Li-Fraumeni Syndrome (LFS) is an uncommon, inherited, autosomal dominant cancer syndrome marked by the early onset of multiple malignancies, particularly breast cancer. It is most commonly linked to germline alterations of the TP53 tumor suppressor gene, an essential regulator of the cell cycle and apoptosis. The penetrance for possible cancer-inducing mutations in TP53 is exceptionally high, approaching 100% in females and about 75% in males, significantly predisposing them to cancer at a young age. In LFS, breast cancer is the most prevalent malignancy occurring before the patient reaches menopause. It tends to be hormone receptor-sensitive and often HER2-positive.
Fig.1 A case study of pathological analysis of LFS-associated breast cancer. (Sasaki R.,
et al., 2022)
Pathogenesis of Li-Fraumeni Syndrome (LFS)-associated Breast Cancer
The pathogenesis of LFS-associated breast cancer is primarily driven by germline mutations in the TP53 gene. These mutations result in a dysfunctional p53 protein, which impairs the cell's ability to repair DNA damage and regulate cell cycle progression. Consequently, cells with DNA damage are more likely to proliferate uncontrollably, leading to the development of cancer. Additionally, the loss of p53 function may also affect the response to chemotherapy and radiation therapy, making these therapeutics less effective and potentially increasing the risk of secondary malignancies. The high penetrance and early onset of cancers in LFS highlight the critical role of TP53 mutations in the pathogenesis of this syndrome.
Diagnostics Development for Li-Fraumeni Syndrome (LFS)-associated Breast Cancer
Histopathologic Analysis
Histopathologic analysis is crucial for characterizing LFS-associated breast cancers. This involves examining tissue samples under a microscope to assess the tumor's histology, grade, and hormone receptor status. Immunohistochemistry is commonly used to determine the expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2). These markers are important for guiding therapeutic decisions, as they can predict the tumor's response to hormone therapy and targeted therapies.
Molecular Profiling
Molecular profiling of LFS-associated breast cancers can provide additional insights into the tumor's biology and potential therapeutic vulnerabilities. This may include next-generation sequencing to identify mutations in other genes that may contribute to cancer development or progression. Molecular profiling can also help identify potential targets for novel therapies, such as PARP inhibitors or immune checkpoint inhibitors, which may be particularly effective in cancers with specific genetic alterations.
Therapeutics Development for Li-Fraumeni Syndrome (LFS)-associated Breast Cancer
- Chemotherapy: Chemotherapy, including anthracycline-based regimens, is commonly used in the adjuvant setting. However, the response to chemotherapy in LFS-associated breast cancer may vary, with some studies reporting impaired response due to p53 dysfunction.
- Gene Therapy: Research into gene therapy approaches, such as the introduction of wild-type TP53, is ongoing. Although these therapies are not yet widely available, they hold promise for the future therapeutic of LFS-associated breast cancer.
Table 1. Consensus recommendations for the therapeutics of Li-Fraumeni syndrome. (Sasaki R., et al., 2022)
| Radiation therapy |
RT of the intact breast is contraindicated.
Post-mastectomy RT should only be considered in patients with a significant risk of locoregional recurrence.
[Strength of recommendation: Moderate, Quality of evidence: Low (case-series only)] |
| Surgical therapy |
A mastectomy is the recommended therapeutic option. |
| Systemic drug therapy |
Avoid cytotoxic anticancer drugs that induce DNA damage if possible.
PARP inhibitors: insufficient evidence for moderately penetrant genes, including TP53. |
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 provides all-inclusive diagnostic and therapeutic development solutions for LFS-associated breast cancer. Our offerings include genetic testing, immunohistochemistry, fluorescence in situ hybridization, as well as the creation of innovative drug and therapy strategies.
Diagnostics Development
- Karyotype Analysis Service
- Omics Analysis Service
- Biomarker Development Service
- Artificial Intelligence Service
- Customized Diagnostics Development Service
Therapeutic Development
- Anticancer Peptide
- Gene Therapy
- Immunotherapy
- Monoclonal Antibody
- Phytotherapy
- Small Molecule Drug
- Therapeutic Cancer Vaccine
Disease Models
- Primary Cell Line System
- Heterozygous p53-null Mouse Models
- Humanized p53 knock-in Mouse Models
- MMTV-Neu Transgenic Mice with Altered TP53
The distinct advantages of partnering with Protheragen for LFS-associated breast cancer diagnostics and therapeutics development stem from our integrated expertise and cutting-edge technologies. If you are interested in our services, please feel free to contact us.
References
- Sasaki R., et al. "Lessons learned in practice with Li-Fraumeni syndrome: LFS-related breast cancer treatment strategy and establishment of a surveillance system." Juntendo Medical Journal 68.4 (2022): 405-412.
- Kast, Karin, et al. "Late onset Li-Fraumeni Syndrome with bilateral breast cancer and other malignancies: case report and review of the literature." BMC cancer 12 (2012): 1-7.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
