Intro to Case Flashcards
outline the risk factors of developing breast cancer
- age >60 years
- oestrogen exposure- early menarche, late menopause, oral contraceptive use, HRT
3.lifestyle factors such as obesity, alcohol - family history of breast cancer
what can protect against breast cancer
breastfeeding and physical activity
describe the presentation of breast cancer
- lump in the breast
- a change in size or shape of the breast
- dimpling of the skin or thickening in breast tissue
- presence of inverted nipple
- rash or discharge from the nipple
- swelling or a lump in the armpit
describe the screening of breast cancer
- breast self examination
- mammography- UK national breast screening programme screens all women aged 50-70 every 3 years
- facilitates detection of early breast cancer, reducing mortality by 20-30%
outline the basic treatment options of breast cancer
- surgery
- endocrine therapy
- radiotherapy
- chemotherapy
- MAbs and other target treatments
what does TNM staging stand for
- T- tumour size
- N- lymph nodes
- M- metastasis
describe the tumour size in TNM staging
- T1- <2cm
- T2- 2-5cm
- T3- >5cm
- T4- direct extension to chest wall or skin
describe the lymph nodes in TNM staging
- N1- mobile ipsilateral lymph nodes
- N2- fixed to one another or other structures
- N3- intraclavicular or ipsilateral internal mammary and axillary nodes
describe metastasis in tNM staging
- M0- no distant metastasis
- M1- contralateral lymph nodes or any distant metastases
- Mx- distant metastasis can’t be assessed
outline the grading pathology
- Grade I- well differentiated/low grade
- cancer cells look similar to normal cells and grow very slowly - Grade II- moderately differentiated
- cancer cells look more abnormal and are slightly faster growing - grade III- poorly differentiated/high grade
- cancer cells look very different from normal cells and grow quickly
describe the pathological classification
- 70-80% ductal
- 5-10% lobular
- 10-20% tubular
- 5-10% medullary
- 1-2% mucinous/colloid
- 2% inflammatory
what are the 2 categories in the immunohistochemistry receptor status
- ER- oestrogen receptor and PR- progesterone receptor
- HER2 positive
- human epidermal growth factor receptor type 2
what is the role of the oestrogen and progesterone receptor and describe prognosis
- hormone dependent tumour
- more likely to respond to hormonal treatments
- aromatase inhibitors
- tamoxifen - more favourable prognosis and more common
what is HER2 and describe the prognosis of this receptor status
- a transmembrane tyrosine kinase which regulates growth, survival and migration
- may respond to trastuzumab (herceptin)
- more aggressive and less favourable prognosis
what factors should be considered when considering chemotherapy
- gender, age
- personal and family history
- pathological stage of tumour
- biological characteristics of tumours
describe how molecular assays are used
- uses real time PCR to assess expression of a panel of 21 genes related to tumour proliferation
- gives a validated recurrence score indicating the patients 10 year recurrence risk
- gives a validated prediction as to whether the patient will have additional benefit from chemotherapy compared to tamoxifen alone
- NICE approved for early stage node -ve, ER +, HER2-ve breast cancer
what is the difference between adjuvants and Neo-adjuvant
- adjuvant- after primary surgery
- Neo-adjuvant starts before surgery
- locally advanced tumours
- inflammatory tumours
- to preserve tissue, facilitate less invasive surgery
describe the treatment for early stage, HER+ breast cancer
- surgery- lumpectomy and lymph nodes
- adjuvant chemotherapy including HER2 targeted treatment
- radiotherapy
- endocrine therapy
what does adjuvant chemotherapy consist of
- cyclophosphamide
- an anthracycline- doxorubicin
- a taxane- docetaxel, paclitaxel
- for HER2+, should contain trastuzumab +/- pertuzumab
describe the properties of cyclophosphamide
- alkylating agent- crosslinks DNA strands and inhibits DNA synthesis, transcription and replication
- non cell cycle specific
- a pro drug- activated in liver to phosphoramide mustard
describe the properties of anthracyclines
- creation of free radicals- oxidative damage
- intercalates between base pairs in DNA
- inhibit action of topoisomerase II by stabilising the DNA topoisomerase II complex, preventing re-ligation of the double helix
- non cell cycle specific
describe the properties of taxanes
- enhance the polymerisation of tubulin
- stabilise the microtubule polymer, preventing disassembly of the mitotic spindle
- blocks progression of mitosis, leading to apoptosis
- cell cycle specific- M phase
what is involved in combination chemotherapy
- choose drugs which act at different stages of the cell cycle, with different MOAs to maximise cytotoxic effect and minimise resistance
- lots of different regimes- eg. EC-T
- epirubicin, cyclophosphamide and docetaxel
describe the MOA of trastuzumab
- the only approved HER2 therapy that binds to HER2+ tumour cells and flag them for destruction by immune system
- blocks downstream HER2 signalling to inhibit proliferation of cells
describe the health economics related to the sue of trastuzumab
- hazard ratio= 0.54- trastuzumab halves the risk of relapse
- cost per patient- 25k
- NNT=12= £300k
- originally rejected by NICE but reviewed after public pressure
- biosimilars have reduced the price
how is pertuzumab used
can be used in combination with trastuzumab to provide a more comprehensive block
describe the results of the intention to treat population category in the APHINITY trial
- pertuzumab vs placebo
- 19% risk reduction
- overall 1.7% reduction in percentage of patients relapsing after 4 years
describe the results of the population with node negative disease category in the APHINITY trial
- little differences between the 2 groups
describe the results of the population with node positive disease category in the APHINITY trial
- 3.2% Absolute reduction in relapses over 4 years
- 23% risk reduction
- Cost per QALY <£20k
- NICE approved for lymph node positive disease only
outline the dosage regime of EC100T and T and P
- Epirubicin 100mg/m2 IV bolus
- cyclophosphamide 500mg/m2 IV bolus
- on day 1 of a 21 day cycle for 3 cycles, then - docetaxel (taxotere) 100mg/m2 iV infusion in 250ml 0.9% sodium chloride over 1 hour
- on day 1 of a 21 day cycle for 3 cycles - Trastuzumab and pertuzumab 1200/600mg LD SC over 8 mins (cycle 1) then 600/600mg SC over 5 mins (cycle 2+)
- on day 1 of a 21 day cycle for 18 cycles
