Breast Cancer Flashcards by Alex Martin

How many womem develop breast cancer?

1/11

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What is the mortality rate of breast cancer?

20%

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Where in the breast do most breast cancers arise from?

Terminal Duct Lobular Unit

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What are some risk factors associated with breast cancer?

Age
Gender
Diet
family history
Hormones (pregnancy, lactation, menopause)
Previous Breast cancer 
Radiation

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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

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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

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What % of breast cancer appears inherited?

5-10%

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What genes are associated with familial breast cancer?

90% = BRCA1 or BRCA2

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What is BRCA1?

Tumour supressor gene on chromosome 17
500 mutations reported
Protein with role in genomic stability

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How is BRCA1 passed?

Autosomal dominant tranmission

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With BRCA1 mutation, what is chance of breast cancer?

50-85% often early onset
Ovarian cancer = 15%
Second primary breast cancer = 40 - 60%

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What is BRCA2?

Tumour supressor gene on chromosome 13
Genomic stability
~300 different mutations

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How is BRCA2 passed?

Autosomal dominant

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What risks associated with BRCA2 mutation?

6% breast in men

50-85% breast in women

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What symptoms are associated with breast cancer?

Breast lump
Nipple discharge
Skin changes

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How does pathologist play a role in predicting prognosis?

Examines histology

Plays role in diagnosis and prognosis

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What are the two breast cancer histological types?

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Non-infiltrating

Infiltrating

What cancers are non-infiltrating?

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Ductal carcinoma in situ
Lobular carcinoma in situ

Non metastatic

What cancers are infiltrating?

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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?

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Tumour Size
Histological Grade
Stage of disease (TNM)

What is the histological grade of breast cancer?

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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?

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Characterizing breast cancer

Phenotypically identical breast cancers may be genetically distinct and have different clinical courses

What are current treatments for breast cancer?

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Surgery (mastectomy)
Drugs
  - Antioestrogens
   - Aromatases
   - LHRH Antagonists
Radiation, chemo and targeted therapy

After surgery etc, how is breast cancer further managed?

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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

Breast Cancer Flashcards

(42 cards)