Breast Cancer Flashcards
How many womem develop breast cancer?
1/11
What is the mortality rate of breast cancer?
20%
Where in the breast do most breast cancers arise from?
Terminal Duct Lobular Unit
What are some risk factors associated with breast cancer?
Age Gender Diet family history Hormones (pregnancy, lactation, menopause) Previous Breast cancer Radiation
What type of proliferative duct lesions are there?
Epithelial Hyperplasia = 1.5x increase chance
Atypical epithelial hyperplasia = 4-5x increase
Low grade ductal carcinoma in situ = 10x chance
High grade ductal carcinoma in situ = 10x chance
What type of lobule lesions are there?
ALH = Atypical lobular hyperplasia = 4-5x chance LCIS = Lobular carcinoma in situ = 10x chance
Lobules expanded by proliferatoin of cells with uniform appearance
What % of breast cancer appears inherited?
5-10%
What genes are associated with familial breast cancer?
90% = BRCA1 or BRCA2
What is BRCA1?
Tumour supressor gene on chromosome 17
500 mutations reported
Protein with role in genomic stability
How is BRCA1 passed?
Autosomal dominant tranmission
With BRCA1 mutation, what is chance of breast cancer?
50-85% often early onset
Ovarian cancer = 15%
Second primary breast cancer = 40 - 60%
What is BRCA2?
Tumour supressor gene on chromosome 13
Genomic stability
~300 different mutations
How is BRCA2 passed?
Autosomal dominant
What risks associated with BRCA2 mutation?
6% breast in men
50-85% breast in women
What symptoms are associated with breast cancer?
Breast lump
Nipple discharge
Skin changes
How does pathologist play a role in predicting prognosis?
Examines histology
Plays role in diagnosis and prognosis
What are the two breast cancer histological types?
Non-infiltrating
Infiltrating
What cancers are non-infiltrating?
Ductal carcinoma in situ
Lobular carcinoma in situ
Non metastatic
What cancers are infiltrating?
Invasive ductal carcinoma
Invasive lobular carcinoma
Special types regarded as variants of IDC
- Tubular
- Mucinous
- Cribriform
- Papillary
- Medullary
Potentially metastatic
What factors are used to predict prognosis in breast cancer?
Tumour Size
Histological Grade
Stage of disease (TNM)
What is the histological grade of breast cancer?
Assessed on architecture, cytology and proliferative activity
- Grade 1 = well differentiated = good
- Grade 2 = poorly differentiated = bad
What is the major focus of breast cancer research of pathologists and scientists?
Characterizing breast cancer
Phenotypically identical breast cancers may be genetically distinct and have different clinical courses
What are current treatments for breast cancer?
Surgery (mastectomy) Drugs - Antioestrogens - Aromatases - LHRH Antagonists Radiation, chemo and targeted therapy
After surgery etc, how is breast cancer further managed?
Histopathological characteristics and stage Surgical margins / sentinel node status Biological characteristics (biomarkers)
How are breast cancer biomarkers studied / quantified?
Immunohistochemistry
Gene expression analysis
Is oestrogen a steroid?
Yus
Are steroid hormone receptors linked with breast cancer?
Yes, in particular ER, PR, AR (androgen receptor)
How do steroid receptors/ligands work?
Steroid hormones bind to receptors in nucleus
Complex binds to DNA response elements in promoter region of regulated genes
Involved in cell growth
Is breast cancer stimulated by oestrogens?
Yes
Thus treated with anti-oestrogen therapies/ drugs
How can you detect hormone receptors?
Hormone receptor assays
What is % chance to respond to treatment if ER+ and PR+?
80%
What is % chance to respond if ER+ PR- or ER- PR+?
40%
What is % chance to respond if ER- PR-?
10%
How do anti-oestrogens work?
Influence G1 phase of cell cycle
1) Decrease cyclin D1 protein and mRNA levels
2) decline in cyclin D1 cdK4 activity
3) Decreased phosphorylation of Rb
Impedes S phase entry
Also increase levels of CDK inhibitors p21 and p27
What drugs target the oestrogen receptor?
Antiestrogens,
- tamoxifen, Raloxifene, Fulvestrant
What drugs inhibit conversion of androstenedione and testosterone to oestradiol?
Aromatase inhibitors
- Letrozole
What drugs eventually cause shutdown of GnRH? (gonadotropin releasing hormone)?
LHRH agonists
What is HER2?
Human Epidermal Growth Factor Receptor 2
Encodes protein p185
Amplification stimulates cell growth
- Associated with 30% metastatic BCs
How does HER2 work?
protein monomer
Binds other members of HER forming heterodimers
Ligand binding stabilises and activates cytoplasmic signal proteins
What are some indicators of increased HER2 production?
1) Increase in gene copy number
2) Increase in mRNA transcription
3) Increase in cell surface receptor or protein expression
4) Increase in release of receptor extracellular domain
What drugs target HER family of receptors?
Herceptin (Trastuzumab)
- Monoclonal antibody against the extracellular domain of HER2
IV infustion
What subtypes can cancer be expressed as?
Basal, erb-B-2 and luminal subtypes
