Molecular Breast Cancer Flashcards
BRAC1
Tumor suppressor gene on chromosome 17
Engages in double-stranded break repair (Nonhomologous end joining, homologous recombination), cell cycle checkpoints, mitotic spindle pole assembly, separation of sister chromatids, centrosomal duplication
Familial vs sporadic breast cancer
10-15% due to multifactorial familial risk (5% due to familial mutations in BRAC1 and BRAC2)
80% is sporadic, no associated family history
BRAC2
Tumor suppressor gene on chromosome 13
DSBR, meiosis recombination functions
Carcinogenesis from BRAC1 and BRAC2 mutations
Double-stranded breaks from failure to repair can lead to cancer
Genomic instability resulting in gross chromosomal arrangements, chromosomal missegregations, and aneuploidy
Human epidermal growth factor receptor 2 (HER2)
Membrane tyrosine kinase
Oncogene that is overexpressed in 20% of breast cancers
Transcription factors activated by pathway regulate genes involved in cell proliferation, survival, differentiation, angiogenesis, invasion, and metastasis
Tests used to detect HER2 amplification in breast cancer samples
Immunohistochemistry (IHC): staining that detects HER2 protein overexpression using monoclonal or polyclonal antibodies to bind to the protein
In situ hybridization: labeled DNA probe complementary to genomic sequences of HER2 are hybridized to sample tissue
- FISH: shows number of copies of HER2
- CISH: light microscopy, chromogens used for detection of gene amplification but can’t determine exact copy number
- SISH: silver-enhanced, quantitative scoring of gene copy number
Trastuzumab
Target HeR2 positive breast cancer
Humanized monoclonal antibody that recognizes external domain of HER2
Interrupts intracellular signaling, target cells for destruction by immune system
Lapatinib
Small molecule tyrosine kinase inhibitor that blocks kinase activity of HER1 and 2, inhibiting signaling
