GENOMIC MEDICINE IN RISK PREDICTION AND SCREENING
Risk Factors for Breast Cancer
Female
Age: 75% occur over 50 years, mean age is 64 years.
Pregnancy: protected if full term, pregnancy <30years.
Family history: increases with each 1st degree relative
Race: lower incidence but more aggressive disease in women of African descent.
Aetiology of Breast Cancer
Unknown.
Genetic factors: 5% of breast cancers due to inherited mutation BRCA1/BRCA2/p53.
Estrogenic exposure: oophorectomy reduces risk of breast cancer by 75%. HRT increases risk (only if
unopposed oestrogen).
Lifestyle: diet, exercise, alcohol.
Morphological Classification of Breast
Cancer
a) In-stu
- Lobular
- Ductal (high grade, low grade,
intermediate grade)
- Paget’s disease
b) Invasive
- Lobular
- Ductal. No special type
- Special types
Infiltrating Ductal Carcinoma
, o The most common subtype.
o Very variable appearance.
o Need to exclude “special types” to get diagnosis.
o Outcome most variable of all subtypes.
Infiltrating Lobular Carcinoma
o The second most common tumour.
o Multifocality.
o Bilaterality- 15-30%.
o Metastasis to serous cavities and abdominal organs.
o Lacks E-Cadherin.
Tubular Carcinoma
o Tubules >90%.
o Admixed cribriform elements (>50%)
o 2-3% in symptomatic setting.
o Up to 20% in screening.
o Excellent prognosis.
Prognostic Factors in Breast Cancer
Tumour type
Tumour grade
Tumour size
Tumour spread (lymph node status)
Biological markers
Challenges in Breast Cancer
Better predict prognosis to determine who requires adjuvant treatment.
Predict response to hormone and chemotherapy.
Identify novel therapeutic targets.
‘patient tailored therapy’.
Gene Expression Arrays
Conventionally require large amounts of fresh tissue.
Amplification techniques.
Formalin fixed paraffin embedded tissue.
Chips may be commercial or ‘in house’
Genome-wide.
Limited gene set. Cancer specific chips.
Risk Factors for Breast Cancer
Female
Age: 75% occur over 50 years, mean age is 64 years.
Pregnancy: protected if full term, pregnancy <30years.
Family history: increases with each 1st degree relative
Race: lower incidence but more aggressive disease in women of African descent.
Aetiology of Breast Cancer
Unknown.
Genetic factors: 5% of breast cancers due to inherited mutation BRCA1/BRCA2/p53.
Estrogenic exposure: oophorectomy reduces risk of breast cancer by 75%. HRT increases risk (only if
unopposed oestrogen).
Lifestyle: diet, exercise, alcohol.
Morphological Classification of Breast
Cancer
a) In-stu
- Lobular
- Ductal (high grade, low grade,
intermediate grade)
- Paget’s disease
b) Invasive
- Lobular
- Ductal. No special type
- Special types
Infiltrating Ductal Carcinoma
, o The most common subtype.
o Very variable appearance.
o Need to exclude “special types” to get diagnosis.
o Outcome most variable of all subtypes.
Infiltrating Lobular Carcinoma
o The second most common tumour.
o Multifocality.
o Bilaterality- 15-30%.
o Metastasis to serous cavities and abdominal organs.
o Lacks E-Cadherin.
Tubular Carcinoma
o Tubules >90%.
o Admixed cribriform elements (>50%)
o 2-3% in symptomatic setting.
o Up to 20% in screening.
o Excellent prognosis.
Prognostic Factors in Breast Cancer
Tumour type
Tumour grade
Tumour size
Tumour spread (lymph node status)
Biological markers
Challenges in Breast Cancer
Better predict prognosis to determine who requires adjuvant treatment.
Predict response to hormone and chemotherapy.
Identify novel therapeutic targets.
‘patient tailored therapy’.
Gene Expression Arrays
Conventionally require large amounts of fresh tissue.
Amplification techniques.
Formalin fixed paraffin embedded tissue.
Chips may be commercial or ‘in house’
Genome-wide.
Limited gene set. Cancer specific chips.
