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Cancer part 2

Sem 1 - breast cancer

What happens to the cortex of an abnormal lymph node? Tends to become markedly hypoechoic (gives off few echoes in ultrasonography)
What is a sentinel lymph node? The first lymph node 'downstream' from the cancer in the lymph node system
What do pathologists/radiologists look at to see if a lump is a tumour and cancerous? The hilum to cortex ratio
What happens to the hilum:cortex ratio if the tumour is cancerous? Hilum decreases in size and the cortex becomes thicker
What other changes occurs to a cancerous lymph node? It becomes rounder in shape
Where is the BRCA1 gene located? 17q21
Where is the BRCA2 gene located? 13q12.3
What do these genes produce? Tumour suppressor proteins
In which ethnicities are BRCA1 and BRCA2 gene mutations common? Ashkenazi genes, Norwegians, Dutch and Icelandic people
How does BRCA1 usually function? -BRCA1 provides instructions for making a protein that is usually involved in repairing damaged DNA -In the nucleus of many normal types of cells the BRCA1 protein interacts with several other types of proteins (eg RAD51,BARD1) to mend breaks in DNA
What family of genes does BRCA1 belong to? RING-type zinc fingers (RNF)
In the zinc finger proteins of these genes, what amino acids do the domains contain? Cysteine and histidine
What enzyme activity do Ring-type zinc finger proteins have? E3 ubiquitous protein ligase
How are cancer risks caused by BRCA1 and BRCA2 mutations passed on? In an autosomal dominant manner
What are the different variation of mutations that can occur? (relating to cancer) -Deleterious mutation -Suspected deletions -Variant of unknown significance -Favour of polymorphism -Benign polumorphism
What are some tumour suppressor genes? APC, p53 and BRCA1
When can BRCA1 gene mutations be tested for? -If there is a strong family history of breast cancer -Most people need a living relative with breast cancer -If a faulty gene is found in the individual with cancer, researchers can look for the same injury in another individual
What are proto-concogenes? Inactive forms of oncogenes. They promote cell division, survival and growth
What are some examples of proto-oncogenes? K-Ras, PRL-3, ER and HER2
When might cancer be related to an inherited gene? -2 or more close blood relatives on the same side of the family affected by the same type of cancer -Close relative has had more than one primary cancer -Members of a family have had certain cancers at a young age -You have Polish or Jewish ancestory
What type of mutations commonly occur in proto-oncogenes? Missense mutations
What type of mutations in tumour suppressor genes? Deletions that remove the gene, nonsense mutations that truncate the protein
What are the 3 main categories of carcinogens? Chemical, radiation and viruses
What is the multiple theory of carcinogenesis? -As tumours progress, genetic damage accumulates -Abnormal cells are able to survive -Abnormal cell proliferative -Eventually invade surrounding tissue -Later spread to other parts of the body
What is a mammogram? A low-does x-ray of the breast
What ages does the NHS screening programme carry out mammograms on women? Age 50-70 (Currently being expanded to between 47-73 years)
What is the procedure of a mammogram? Radiographer positions one breast at a time between two small flat plates on the x-ray machine. Plates press firmly onto the breast for a few moments to take the x-ray. Compression of the breast helps to give a clearer picture. You have two x-rays on each
Why might a breast ultrasound be carried out? If you're under 35 (as younger women have denser breasts) or to see if the lump is solid or contains a liquid (cyst)
What non-cancerous growths can breast ultrasounds show? Cysts: Fluid filled sac Fibroadenomas: non-cancerous solid growths Lipomas: non-cancerous fatty lumps that can occur anywhere
What signs are looked for during inspection of the breasts? -Variation in breast size and contour -Whether there is an inverted nipple (uni or bilateral) -Any oedema -Redness or retraction of the skin -Peau d'orange (dimpling of the skin)
What follows the inspection of the breast? Palpation of the breast
What 3 search patterns are used to search (palpate) the breast? -Radial spoke method -Concentric spoke method -Vertical strip method
In which quadrant of the breast are cancers most common? Superior lateral quadrant (45%)
What are the different types of breast biopsy? Needle aspiration, needle biopsy, vacuum biopsy, punch biopsy, excision biopsy (surgery), wire guided biopsy
What are four different classes of breast cancer? -Endocrine receptor (oestogen or progesterone) positive -HER2 positive -Triple negative; not positive for ER, PR, HER2 receptor -Triple positive; for ER, PR and HER2 receptors
What percentage of breast cancers are ER positive? 75%
What therapy is used for breast cancers that are ER and/or PR positive? Endocrine therapy
What drug might women with ER positive cancer take? Tamoxifen (or aromatase inhibitors such as anastrazole)
What class of drugs does Tamoxifen belong to? Selective oestrogen receptor molecules (SERMs)
How does Tamoxifen act? -Binds to oestrogen receptors (antagonist) -Results in conformational change in receptor -Causes a blockage or change in the expression of ER dependent genes
What does prolonged binding of Tamoxifen to the nuclear chromatin of genes result in? -Reduced DNA polymerase activity -Impaired thymidine utilisation -Blockade of oestradiol uptake -Decreased oestrogen receptors
Which gene codes for the HER2 protein? ERBB2 gene
What type of gene is this, and where is it located? A proto-oncogene at 17q12
What is this family of genes composed of? Four plasma-membrane-bound receptor tyrosine kinases. All four contain an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain.
What does HER2 stimulate? Cell proliferation
Which drug is often used for women with HER2 positive breast cancers? Herceptin or monoclonal antibody therapy called Trastuzumab
What is the drug Herceptin and how does it work? -Recombinant IgG I Kappa, Monoclonal antibody -Selectivity binds with high affinity in cell-based assay in growth factor protein -It binds to the HER2 proto-oncogenes and kills the HER2 positive cells
What are the different types of breast conserving surgery? -Lumpectomy (removal of the lump) -Quadrantectomy (removal of one quadrant) -Segmented mastectomy (removal of the cancer as well as some of the breast cancer as well as some of the breast tissue around the tumour and lining over the chest muscle)
What will the type of breast conserving surgery of a woman has depend upon? -Size if the cancer in the breast -Whether it has spread to any other part of the body -The size of the woman's breast -Her personal wishes and feelings
What usually follows breast conserving surgery? Radiotherapy
Why is a border of healthy tissues taken from the cells surrounding the tumour? These cells are examined by a pathologist for a clear margin. If there isn't a clear margin, more surgery may be required
What are the 3 types of mastectomies? -Total mastectomy -Modified radical mastectomy -Radical mastectomy
Which type of mastectomy is used to treat ductal carcinoma in situ? Total mastectomy
When might radiotherapy be used for women with breast cancer? -4 weeks after breast-conserving surgery -Possibly after chemotherapy -If the cancer has spread to the surrounding lymph nodes but only some were removed -After a mastectomy if there's an increased risk of cancer returning to the same area
Outline the process of external radiotherapy? -Each treatment is in the hospital radiotherapy department -Daily sessions (10-15 mins) -Usually for 3 weeks to the whole breast area, and close to where lymph nodes are situated
What are potential side effects of radiotherapy? -Reddening and soreness of the skin -Tiredness -Feeling sick (nausea)
What are possible long term side effects of radiotherapy? -telang iectasia (damage to small blood vessels in skin,causing red 'spidery' marks) -Skin may have a slightly darker skin tone and feel firmer -Rarely, a few women develop breathlessness (recovers after 2-4 weeks) -Rarely radiotherapy my weaken ribs
Why might some women choose immediate reconstruction surgery? Only one anaesthetic, one hospital stay, and one recovery period
Why might some women choose delayed reconstruction surgery? Shorter recovery period, may be necessary to wait if they are going to have radiotherapy or chemotherapy
What are two types of breast reconstruction? -Prosthetic reconstruction (artificial implants are used) -Autogenous reconstruction (tissue from elsewhere is used to create the breast mound)
How often are patients seen once their cancer treatment has finished? -Around 6-8 weeks after their treatment has finished -Then every few months -Then reduced to once a year -Others may be required to contract their GP or have telephone consultations
What 3 aspects of cancer might psychology play a role in? Susceptibility, progression and longevity
What four common clinically significant symptoms/illnesses do women with newly diagnosed breast cancer often exhibit? -Severe emotional distress -Major depression -Post traumatic stress disorder -Generalised anxiety disorder
What psychosocial factors may affect the initiation and promote of cancer? Behavioural factors, Stress, Life Events, Control, Depression, Personality, Hardiness (H may be protective against developing cancer)
What is the type-C personality? And how does this relate to cancer? Individuals react to stress with hopelessness and helplessness and individuals who repress emotional reactions to life events. These people are 10x more likely to get cancer
Created by: SandersE