Anatomy - Breast cancer Flashcards
What are the properties of malignant lumps?
- Irregular and hard
- Fixed to chest wall
- Skin above is tethered
- Palpable lymph nodes in axilla
- Indrawn nipple
- Bone tenderness/pain
What data is required for breast cancer diagnosis?
- Tumour size
- Lymph node staging
- Histological type and grade
- Vascular invasion
- Excision margins
- In-situ components
- Hormone and HER2 status
Where in the breast does breast cancer usually occur?
Lobular cells and duct
What does histology of a high grade tumour look like?
What type of tumour is this?
Oestrogen receptor positive tumour
What type of tumour is this?
Oestrogen receptor negative tumour
What type of tumour is this?
HER2 receptor positive tumour
What is the triple approach to breast cancer diagnosis?
- Physical examination
- Mammogram
- Biopsy
What are the 4 types of chemotherapy?
- Neo-adjuvant –> shrinks tumours before surgery
- Adjuvant –> follow up after surgery
- Palliative –> relieves symptoms
- Immunotherapy
What are the properties of anti-cancer drugs?
- Use cytotoxic drugs
- Kill rapidly dividing cells
- Target DNA synthesis and mitosis
- Given in cycles
What does the treatment cycle graph for chemotherapy look like?
What is the function of anitmetabolites?
- Interfere with metabolic pathways in DNA synthesis
- Folate antagonist –> inhibit purine and pyramidine synthesis
- Methotrexate
- Dihydrofolate reductase inhibitor
What is the function of false substrates?
- 5-Fluoruracil
- Similar to pyrimidines
- Inhibits thymidylate synthase
- Incorporated into DNA as false metabolites
- Lead to DNA damage
What is the function of alkylating agents?
- Cyclophosphamide
- Causes chemical cross-linking of DNA
- Leads to defective DNA replication
What is the function of platinum compounds?
- Inhibit DNA synthesis by cross-linking guanine residues
- nausea though
What is the function of antibiotics in chemotherapy?
- Interfere with nucleotide synthesis by intercalating between DNA strands
- Inhibit topoisomerase
- Generate free radicals
What is the function of topoisomerase inhibitors?
- Inhibit topoisomerase ii
- Prevents ligation of DNA
- Leads to breaks in DNA strand
What is the function of microtubule inhibitors?
- Vinca alkaloids block formation of mitotic spindle
- Taxanes stabilise spindle fibres and make them rigid so cells can’t separate
What are all the chemotherapy side effects?
- Inhibit all fast-growing cells
- Myelosuppression
- Reduced white cell counts
- Infections
- Nausea (+ with platinum compounds)
- Hair loss
- Infertility
- Cardiotoxicity (anthracycline antibiotics)
How do you reduce all of the chemotherapy side effects?
(myelosuppression, reduced white cell counts, infections, nausea, hair loss, infertility, cardiotoxicity)
- Monitor blood counts and Hb
- Colony-stimulating factors
- Antibiotics and antifungals
- Anti-emetics
- Cool cap
- Max lifetime dose and regular ECGs
What are the types of palliative care?
- Pain relief
- Strong opioids (morphine, diamorphine, fenatyl patches
- Syringe drivers
- Hospice care
What are the benefits of molecular testing of cancer cells?
- Determines receptor expression
- Can effectively be targeted
What is the function of tamoxifen?
- Blocks oestrogen as is selective oestrogen-receptor modulator
- Prevents breast cancer
- Reduces oestrogen-driven breast cancer growth
- Used in ER+ breast cancer
- Guven after surgical removal
- A receptor modulator
What is the function of aromatase inhibitors?
- Prevent peripheral conversion of oestrogen in post-menopausal women
- Tamoxifen alternative
- Inhibit aromatase enzymes that convert androgens to oestrogen
What are the properties of HER2?
- Overexpression in some breast cancers
- Phosphorylates tyrosine - dysregulation of cell cycle - cancer
- Naturally present in low levels
- Due to oncogene
- Treatment = trastuzumab
What is the mode of action of trastuzumab?
- Monoclonal antibody
- Targets HER2 - slowing of cell replication
- Used in early and metastatic breast cancer with HER2 positive tumours
What is the functions of EGF receptor kinase?
- ‘Small molecule’ approach
- Used in lung and pancreatic cancers
- Inhibits tyrosine kinase activation - no gene transcription or cell cycle dysregulation - apoptosis
What are the properties of tyrosine kinase activity?
- Philadelphia chromosome = associated with chronic myeloid leukaemia
- Philadelphia chromosome = produces bcr-abl protein
- Bcr-abl protein has tyrosine kinase activity
- Chronic myeloid leukaemia = ‘Philadelphia positive’
What is imatinib?
Tyrosine kinase inhibitor
+ effective for chronic myeloid leukaemia
What is the function of PARP inhibitors?
- Enzyme which repairs DNA
- Repairs single strand breaks in DNA
- Prevents double strand repair –> cell death
- BRCA gene association
- Used in chemo-resistant ovarian cancer
What is the function of proteasome inhibitors?
- Proteasomes degrade proteins but some proteins kill cancer (pro-apoptotic factors)
- Inhibits intracelular proteasomes - altered intracellular protein regulation
- Used in multiple myeloma (bone cancer/cancer of plasma-producing cells in bone marrow)
What are the properties of anti-VEGF?
- Vascular endothelial growth factor
- Secreted to promote angiogenesis
- Leads to blood vessel growth to support metastasis
- Used in renal carcinoma
