Breast Cancer Flashcards
What causes breast cancer?
A combination of genetic and environmental risk factors
A genetic mutation occurs in tumour suppressor genes BRCA1 and 2 which are responsible for ensuring function of DNA repair or arresting cell cycle
What are the risk factors for breast cancer?
Age > 50 Earl menopause Obesity Alcohol (>5u/day) Smoking No previous breast feeding Lifetime oestrogen exposure Socioeconomic status Race
How does breast cancer present?
Lumps Skin dumpling Inverted nipples Nipple discharge Breast pain Change is breast size/shape Axilliary lymphadenopathy
How can you diagnose breast cancer?
Palpation - identify characteristics of lump (size, texture, can it move easily?), benign often distinct from malignant
Mammography Ultrasonography Biopsy Fine needle aspirate CT scan
What is the first line treatment for breast cancer?
- Simple mastectomy (removal of breast, tumour and lymph nodes, pectoralis major and minor)
- Modified mastectomy (removal of breast, lymph nodes and pectoral is muscle lining)
- Wide local excision (cut section out bigger than tumour
- Quadrantectomy
IN COMBINATION WITH
- Chemotherapy
- Radiotherapy
- Hormonal therapy
- Biological therapy (Trastuzamab)
How is tumour growth stimulated in breast cancer?
The presence of oestrogen
How would you reduce tumour growth?
Selective Oestrogen receptor modulators (Tamoxifen)
Aromatase enzymes (Letrozole)
Ovarian ablation in premenopausal women
reducing exposure to oestrogen reduces tumour growth
How does Tamoxifen work?
It is a selective oestrogen receptor antagonist
It binds to the oestrogen receptor to prevent oestrogen from binding
This slows down proliferation of cancer cells driven by oestrogen
Therefore it is a cytostatic drug
How do aromatase inhibitors (Letrozole) work?
They bind to the aromatase enzyme and prevent it from converting androgens into oestrogen
This prevents tumour growth
When is Tamoxifen started? State the dose
It is started after chemotherapy
Dose = 10mg BD or 20mg OD for 5 years
What is a benefit of Letrozole compared to Tamoxifen?
Neoadjuvant use of Letrozole has been shown to result in more women retaining their breast than for tamoxifen
How does Trastuzumab work?
It is a monoclonal antibody (immune checkpoint inhibitor)
That targets the Her-2 receptor which over expressed on tumour cells
It is licensed for metastatic disease
How is Trastuzamab administered?
IV infusion given as a loading dose of 4mg/kg and then started 1 week later at 2mg/kh
What is the main disadvantage of Trastuzumab?
Implicated in cardiotoxicity especially when used with anthracyclines
How is radiotherapy used in breast cancer?
Used as an adjuvant to eradicate local spread following tumour excision
What combinations of chemotherapy are used for breast cancer?
Cyclophosphamide Methotrexate Epirubicin 5-FU Doxorubicin & Taxanes (Docetaxel)
Which 2 agents are typically used in the treatment for breast cancer?
Cyclophosphamide
Doxorubicin
What is the main side effect of cyclophosphamide?
An alkylating agent
/ Pro drug that is activated by liver metabolism
Acrolein is a urinary metabolite which is very toxic to the urinary tract
Can lead to haemorrhagic cystitis
What is the treatment of haemorrhagic cystitis?
Mesna given routinely to pts on IV high dose cyclophosphamide
It reacts with acrolein and neutralises it in the urinary tract to prevent toxicity
What is the main side effect of Doxorubicin?
Development of cardiomyopathy resulting in a reduced ejection fraction
Occurs due to cumulative dosages of the drug so a limit of 450mg/m2 is given in any tx course
Weekly low dose administration may result in less toxicity
Staging of breast cancer
T0 = No tumour T1 = less than 2cm T2 = more than 2cm less than 5cm T3 = more than 5cm T4 = fixation to chest wall/ulceration
N0 = No palpable axilliary nodes N1a = palpable nodes do NOT contain tumour N1b = palpable nodes contain tumour N2 = Nodes more than 2cm fixed to one another and deep structure N3 = Supraclavicular/infraclavicular nodes
M0 = no distant metastases M1 = distant metastases present
What are the haemorrhagic risk factors?
High dose IV >2g
Previous pelvic irradation
Describe the structure of SERMs
- lack steroid structure of oestrogens
- but possess tertiary structure so can bind to oestrogen receptor
why is the binding to selective of SERMs
- differential ostrogen receptor expression in a given target tissue
- differential oest receptor confirmation on ligand binding
- differential expression and binding to the oest receptor of co regulator proteins
