[Relevant mutations in predictive breast cancer pathology].

Area of Science:

• Oncology
• Molecular Pathology
• Genetics

Background:

• Immunohistochemistry has long been standard in breast cancer classification.
• Predictive molecular pathology is increasingly vital due to new targeted therapies for metastatic disease.
• In situ hybridization for HER2 amplification is an established molecular diagnostic.

Purpose of the Study:

• To highlight the growing importance of predictive molecular pathology in metastatic breast cancer.
• To review key molecular alterations and their corresponding targeted therapies.
• To underscore the shift from traditional methods to molecular diagnostics.

Main Methods:

• Review of current literature on predictive molecular pathology in breast cancer.
• Identification of key gene mutations (BRCA1/2, PIK3CA, HER2, ESR1, tropomyosinreceptor kinase) and their clinical relevance.
• Correlation of molecular targets with approved or investigational therapies.

Main Results:

• BRCA1/2 mutations mandate PARP inhibitor use.
• PIK3CA mutations (up to 40% in luminal cancers) enable alpelisib treatment.
• HER2 alterations (amplification/mutation) guide tyrosine kinase inhibitors (tucatinib/neratinib).
• ESR1 mutations (up to 30% in treated luminal cancers) confer resistance to aromatase inhibitors.
• Tropomyosinreceptor kinase mutations are common in secretory breast cancers (up to 50%).

Conclusions:

• Predictive molecular pathology is essential for personalized treatment strategies in metastatic breast cancer.
• Molecular profiling identifies actionable targets for novel therapeutics.
• The field is rapidly evolving, offering new hope for patients with advanced disease.