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PATH3309 > Breast Cancer > Flashcards

Breast Cancer Flashcards

1
Q

How many womem develop breast cancer?

A

1/11

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2
Q

What is the mortality rate of breast cancer?

A

20%

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3
Q

Where in the breast do most breast cancers arise from?

A

Terminal Duct Lobular Unit

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4
Q

What are some risk factors associated with breast cancer?

A 
Age
Gender
Diet
family history
Hormones (pregnancy, lactation, menopause)
Previous Breast cancer 
Radiation
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5
Q

What type of proliferative duct lesions are there?

A

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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6
Q

What type of lobule lesions are there?

A 
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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7
Q

What % of breast cancer appears inherited?

A

5-10%

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8
Q

What genes are associated with familial breast cancer?

A

90% = BRCA1 or BRCA2

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9
Q

What is BRCA1?

A

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

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10
Q

How is BRCA1 passed?

A

Autosomal dominant tranmission

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11
Q

With BRCA1 mutation, what is chance of breast cancer?

A

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

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12
Q

What is BRCA2?

A

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

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13
Q

How is BRCA2 passed?

A

Autosomal dominant

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14
Q

What risks associated with BRCA2 mutation?

A

6% breast in men

50-85% breast in women

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15
Q

What symptoms are associated with breast cancer?

A

Breast lump
Nipple discharge
Skin changes

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16
Q

How does pathologist play a role in predicting prognosis?

A

Examines histology

Plays role in diagnosis and prognosis

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17
Q

What are the two breast cancer histological types?

A

Non-infiltrating

Infiltrating

18
Q

What cancers are non-infiltrating?

A

Ductal carcinoma in situ
Lobular carcinoma in situ

Non metastatic

19
Q

What cancers are infiltrating?

A

Invasive ductal carcinoma
Invasive lobular carcinoma

Special types regarded as variants of IDC

  • Tubular
  • Mucinous
  • Cribriform
  • Papillary
  • Medullary

Potentially metastatic

20
Q

What factors are used to predict prognosis in breast cancer?

A

Tumour Size
Histological Grade
Stage of disease (TNM)

21
Q

What is the histological grade of breast cancer?

A

Assessed on architecture, cytology and proliferative activity

  • Grade 1 = well differentiated = good
  • Grade 2 = poorly differentiated = bad
22
Q

What is the major focus of breast cancer research of pathologists and scientists?

A

Characterizing breast cancer

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

23
Q

What are current treatments for breast cancer?

A 
Surgery (mastectomy)
Drugs
  - Antioestrogens
   - Aromatases
   - LHRH Antagonists
Radiation, chemo and targeted therapy
24
Q

After surgery etc, how is breast cancer further managed?

A 
Histopathological characteristics and stage
Surgical margins / sentinel node status
Biological characteristics (biomarkers)
25
Q

How are breast cancer biomarkers studied / quantified?

A

Immunohistochemistry

Gene expression analysis

26
Q

Is oestrogen a steroid?

A

Yus

27
Q

Are steroid hormone receptors linked with breast cancer?

A

Yes, in particular ER, PR, AR (androgen receptor)

28
Q

How do steroid receptors/ligands work?

A

Steroid hormones bind to receptors in nucleus
Complex binds to DNA response elements in promoter region of regulated genes
Involved in cell growth

29
Q

Is breast cancer stimulated by oestrogens?

A

Yes

Thus treated with anti-oestrogen therapies/ drugs

30
Q

How can you detect hormone receptors?

A

Hormone receptor assays

31
Q

What is % chance to respond to treatment if ER+ and PR+?

A

80%

32
Q

What is % chance to respond if ER+ PR- or ER- PR+?

A

40%

33
Q

What is % chance to respond if ER- PR-?

A

10%

34
Q

How do anti-oestrogens work?

A

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

35
Q

What drugs target the oestrogen receptor?

A

Antiestrogens,

- tamoxifen, Raloxifene, Fulvestrant

36
Q

What drugs inhibit conversion of androstenedione and testosterone to oestradiol?

A

Aromatase inhibitors

- Letrozole

37
Q

What drugs eventually cause shutdown of GnRH? (gonadotropin releasing hormone)?

A

LHRH agonists

38
Q

What is HER2?

A

Human Epidermal Growth Factor Receptor 2
Encodes protein p185
Amplification stimulates cell growth
- Associated with 30% metastatic BCs

39
Q

How does HER2 work?

A

protein monomer
Binds other members of HER forming heterodimers
Ligand binding stabilises and activates cytoplasmic signal proteins

40
Q

What are some indicators of increased HER2 production?

A

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

41
Q

What drugs target HER family of receptors?

A

Herceptin (Trastuzumab)
- Monoclonal antibody against the extracellular domain of HER2

IV infustion

42
Q

What subtypes can cancer be expressed as?

A

Basal, erb-B-2 and luminal subtypes

PATH3309 (14 decks)

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