Oncology Flashcards
Breast cancer risk factors
Female
Oestrogen exposure
Older age at first birth
Age
1st deg relative
BRCA1/2 - inc. risk if multiple relatives with breast/ovarian ca
Alcohol
BRCA1/2
DNA repair genes
Inherited in Autosomal dominant fashion
50-60% lifetime breast ca risk
Consider tamoxifen pre or post menopausal or raloxifene if post menopausal (40% RR)
Luminal A
ER+, HER2 low, low Ki67
Good prognosis
Treat with endocrine therapy
Luminal B
ER+ but weaker, HER 2 + or -, high Ki67
High recurrence
Benefit from chemo and trastuzumab if HER2 +
HER 2 enriched
ER - HER2 +
Chemo + trastuzumab
TNBC
Chemo
Adjuvant endocrine therapy in breast cancer
All with ER+ve cancer
SERM pre-menopausal
AI post-menopausal (slightly more effective than SERM at reducing recurrence)
5-10yrs of therapy
SERM
Tamoxifen
Antagonists on ER in breast tissue or cancer
Agonist on bone, uterus, liver
Risks: VTE, uterine cancer
Aromatase inhibitors
Anastrozole, letrozole
Block DHEA –> testosterone
Slightly more effective at reducing recurrence compared to SERM
Only use in post-menopausal women
Risks: Decreased BMD, arthralgia
No increase in VTE or uterine Ca risk
Trastuzumab in breast cancer
Monoclonal Ab to HER2
12 months therapy
Risks: reversible cardiomyopathy
No CNS penetration
Pertuzumab in breast cancer
Monoclonal Ab to HER2
Given as neoadvjuvant therapy with pertuzumab in early disease
Or as dual therapy with trastuzumab in metastatic disease
Anthracyclines
Doxorubicin most common
Work by inhibiting topoisomerase (which usually helps to form double stranded DNA complex)
Risks: Irreversible cardio toxicity
Adjuvant radiotherapy in early disease breast cancer
Give if post-breast conserving therapy - recurrence rates similar to mastectomy
Post mastectomy chest wall RTx if >5cm breast cancer or LN +ve
Metastastic ER+ HER2 -
CDK4/6 inhibitor combined with AI or fulvestrant
CDK4/6 inhibitors
Ribociclib/abemaciclib/palbociclib
Block transition from the G1 to the S phase by binding to CDK 4/6 to inhibit Rb protein phosphorylation
Risks: cytopenias, hepatotoxicity
Breast cancer subtypes
Invasive ductal carcinoma (80%)
Invasive lobular carcinoma
Mixed ductal/lobular
Recurrence based on ER status
If ER negative tumours recur - they will recur in first 5 years
ER positive tumours may recur in first 5 years (50%) but can also recur up to 25 years later
Rationale for neoadjuvant therapy in breast cancer
Outcomes are equivalent for neo adjuvant vs adjuvant therapy
Neo-adjuvant can downstage a tumour prior to surgery –> less extensive surgery –> better cosmetic outcome
Everolimus in breast cancer
mTOR inhibitor
Can be used 2nd line in conjunction with AI/fulvestrant in ER + metastatic breast cancer
Risks: stomatitis, pneumonitis
Tumour markers in breast cancer
Tumour markers in breast cancer:
- CA15-3 and CA27-29
- Can aid in assessment of response to systemic therapy
- Not used alone as a reason to change systemic therapy
- May also be elevated in liver failure, B12 deficiency, haemoglobinopathies
Pembrolizumab in breast cancer
PD-L1 inhibitor
In combination with chemo in TNBC metastatic if PD-L1 positive
Olaparib in breast cancer
PARP inhibitor
Used 2nd line or later in metastatic TNBC that is BRCA positive
Risks: decreased Hb, pneumonitis, MDS/leukaemia, Nausea and diarrhoea
Radiotherapy indications in metastatic breast cancer
Bone pain
Spinal cord compression
Cerebral mets
Ulcerating skin/primary lesion
Screening in BRCA + patients
BSE, 6/12 clinical breast examination
Annual mammogram from 40 (or 5 yrs younger than relative)
BRCA genetic testing
All women <70 years old with epithelial ovarian cancer
Melanoma risk factors
> 10 dysplastic naevi
100 common naevi
Fair skin, red hair
High intermittent sun exposure (e.g. blistering sunburn as a child)
Melanoma subtypes
Superficial spreading - most common 70%
Lentigo maligna - high cumulative UV exposure
Acral lentiginous - not caused by UV light. Occurs on palms, soles, under nails. Asians and Black people
Nodular - vertical growth, 50% of melanoma deaths, rapidly growing
Melanoma immunohistochemistry
Positive for S100 and Melan A
Ulceration in melanoma
Upstages diagnosis
Increases risk for metastasis a lot
Stage 1 melanoma
No imaging required
Stage 2 melanoma
WLE and SNB
MRI brain, CT CAP, PET scan
Tx: Nivolumab or pembrolizumab
Stage 3 melanoma
No longer get full LN dissection - completion dissection if disease progression
Pembrolizumab/nivo in all patients
BRAF mutant: Dabrafenib + trametinib (BRAF + MEK inhibitor)
Give vemurafenib if BRAFV600E mutation present
Stage 4 melanoma
10 yr survival 50-60%
Surgical resection of mets if possible3
1st line: ipi + nivo regardless of mutational status (single agent nivo if old or poor ECOG)
2nd line: BRAF mutant: encorafenib + binimetinib. BRAF wildtype: Nivo/relatimab or clinical trial
Predictor of response to immunotherapy
High mutational burden
Melanoma has highest mutational burden
Sunitinib
TKI with anti-VEGF activity
Give in renal cell carcinoma
Hypertension is a predictive marker - treat with ACE-I
Other side effects: ON of jaw, hand-foot skin reaction, hypothyroidism
Pancoast tumour
Apical lung tumour
Usually NSCLC
Can present with shoulder pain or neuropathic arm pain
Horners syndrome via sympathetic ganglion (stellate ganglion) compression
Lung cancer risk factors
Cigarette smoking
Radiation
Environmental toxins: smoking, asbestos, inhaled metals
Pulmonary fibrosis
Genetic factors
Lung cancer subtypes/histology
Adenocarcinoma 40%
Squamous cell 20%
Small cell 13%
Large cell 7%
Other 20%
Small cell lung cancer
Early to metastasise, high mitotic rate
Classically bulky lymphadenopathy
Very chemo/radiosensitive
Almost always non-smokers
Don’t cause clubbing
Can present with paraneoplastic syndromes and/or SIADH
Small cell lung cancer treatment limited stage
Surgery
Chemoradiotherapy
Prophylactic cranial irradiation (brain is sanctuary for micro metastatic disease)
Small cell lung cancer extensive stage treatment
1st line: chemoimmunotherapy and PDL1
Atezolizumab + carboplastin + etoposide
2nd line: topotecan/irinotecan or cyclophosphamide/dox/vincristine
Mesothelioma
Related to Asbestos and tobacco
Asbestos also increases NSCLC risk
Long latency 30-40 years
Incurable
Dual ipi/nivo
NSCLC
Complete full workup including MRI brain, CT CAP, PET
NSCLC stage 1 treatment
Resection if fit
Stereotactic RTx if not fit
NSCLC stage 2 treatment
Resection if fit/amenable
Adjuvant chemotherapy: 4 months cisplatin + cinorelbine
Adjuvant immunotherapy: Atezolizumab if PDL1 >50%
Adjuvant osimertinib
NSCLC stage 3 treatment
Neoadjuvant chemo or immunotherapy to try and downstage to allow resection
Combined chemoradiotherapy
Durvalamab (PD-L1) post chemoRTx improves survival to 50% - no benefit if PDL1 0% or EGFR +
NSCLC stage 4 treatment
Incurable - 6 months survival without treatment
Check for driver mutation and if present treat with specified agent first line (more effective than chemo)
No driver mutation and PDL1 <50% - give platinum doublet + PDL1
No driver mutation and PDL1 >50% - single agent PDL1
EGFR driver mutation
15%
Osimertinib 3rd gen EGFR inhibitor
Good CNS activity
Side effects: Acne-like rash, diarrhoea, pulmonary fibrosis
NO cytopenias
EGFR inhibitor resistance
NSCLC driver mutation present in 15%
Occurs with 1st and 2nd gen EGFR inhibitors after 6-24 months therapy.
Due to T790M mutation
Osimertinib effective against T790M
ALK gene rearrangement driver mutation
NSCLC driver mutation present in 5%
NSCLC associated with EML4-ALK fusion gene
Treat with Alectinib - 62% 5 year survival
Prolonged QT
ROS1 fusion gene driver mutation
NSCLC driver mutation present in 2%
Respond to Crizotinib/lorlatinib/entrectinib
KRAS driver mutation
NSCLC driver mutation present in 25%
More common in smokers (other driver mutations more common in non-smokers)
50% of KRAS mutations are KRAS G12C
Treat with Sotorasib as 2nd line after chemo
ALK inhibitors
Alectinib, crizotinib, ceritinib
KRAS mutation inhibitor
Sotorasib
EGFR inhibitors
Osimertinib, afatinib, gefitinib, erlotinib
MEN1
Autosomal dominant
Tumours of:
-Parathyroid
-Anterior pituitary
-Pancreatic islet cells
90% penetrance by age 50-70
MEN2A
Autosomal dominant with very high penetrance
RET proto-oncogene on chromosome 10
Tumours of:
-Medullary thyroid cancer
-Phaeochromocytoma
-Parathyroid hyperplasia
MEN2B
Autosomal dominant with very high penetrance
RET proto-oncogene on chromosome 10
Tumours of:
-Medullary thyroid cancer
-Phaeochromocytoma
-NOT PARATHYROID
Associated with mucosal neuromas on lips or tongue - not see in 2A
Tumours at an earlier age and more aggressive than 2A
Prostate Cancer screening
PSA 2 yearly from 50-69 and further investigation if PSA >95th percentile for that age group
Prostate cancer localised disease management
Prostatectomy
Radiotherapy
If intermediate risk add on ADT
Prostate cancer advanced disease management
ADT (hormonal therapy or bilateral orchidectomy) combined with novel anti-androgen
Chemotherapy if high volume disease (visceral mets and >4 bone mets)
ADT
Hormonal or bilateral orchidectomy
Hormonal
-GnRH agonists: goserelin, leuprolide
-GnRH antagonists: dagarelix
Need to give androgen receptor blocker for 2 weeks prior to starting GnRH agonist due to flare effect
Novel anti-androgens
CYP17 blockers: Abiraterone (inhibits 17a-hydroxylase)
-Reduced testosterone AND cortisol - give with steroid. Increased mineralocorticoid - hypokalaemia, hypertension, CCF
Androgen receptor blockers: Bicalutamide, enzalutamide
Side effects of ADT
Vasomotor symptoms
Decreased libido
Decreased BMD
Decreased muscle mass
Increased cardiovascular risk factors
Chemotherapy for prostate cancer
Taxane based
Give with ADT if visceral mets or >4 bone mets
Taxanes
Docetaxel, cabazitaxel
Interfere with microtubule growth –> cell cycle arrest in G2/M phase
Also inactivate BCL-2 –> apoptosis
SE: Hair loss, pancytopenia, mucositis/diarrhoea, peripheral neuropathy
Seminoma
AFP not elevated
Testicular cancer markers
AFP and bHCG
Marker of disease severity
Should normalise post radical inguinal orchidectomy
Used for surveillance/follow-up
Adjuvant chemo in localised testicular cancer
Seminoma - carboplatin
NSGCT - BEP
Chemo for metastatic/advanced testicular cancer
BEP
(Bleomycin, etoposide, cisplatin)
Bleomycin
Causes DNA strand scission leading to inhibition of DNA synthesis
G phase, M phase and S phase
Skin side effects most common, pneumonitis in 10%
Etoposide
Topoisomerase II inhibitor
Myelosuppression, alopecia, N/V/D
Cisplatin
Platinum based agent
Binds to DNA and disrupts DNA function
SE: Ototoxicity (30%), tinnitus, myelosuppression, neurotoxicity (peripheral neuropathy), nephrotoxic
Colorectal cancer risk factors
Increased body weight, decreased activity
High consumption of processed meat and alcohol
Low fibre diet
Cigarette smoking
IBD
HNPCC/FAP
HNPCC
AD inheritance, high penetrance
Defect in DNA mismatch repair genes
MLH1, MSH2, MSH6, PMS2
DNA mismatches often occur in areas of micro satellites
Screening for HNPCC: Amsterdam 3:2:1 criteria
Screening with HNPCC: 1-2 yearly colonoscopies from age 25 or 5 years younger than earliest affected relative
Give aspirin in HNPCC - decreases risk of developing CRC
Microsatellite instability
Expansion or contraction of microsatellites seen in tumours compared to normal tissue
Not specific for HNPCC
Can have epigenetic silencing of MLH1 associated with BRAF V600E - generally rules out HNPCC
FAP
1% of CRC
Germline mutation in APC gene on Chromosome 5
Location of mutation associated with severity of polyposis
Screening: sigmoidoscopy from age 10-15. When first adenoma detected do yearly colonoscopies until colectomy
Colectomy indications in FAP
Documented/supsected CRC
Adenoma with high grade dysplasia
Significant symptoms related to polyps e.g. bleeding
Marked increase in number of polyps from one exam to another
Inability to survey colon due to polyposis
Stage 1 CRC management
Surgery
Stage 2 CRC management
Surgery
Consider adjuvant chemo if high risk features
Stage 3 CRC management
Surgery
Adjuvant chemo definitely (CAPOX or FOLFOX)
-Fluoropyrmidine + oxaliplatin
Stage 4 CRC managemenet
Chemotherapy backbone +/- targeted therapy
-VEGF regardless of RAS/RAF status)
-EGFR only in RAS wild-type and left-sided
VEGF inhibitors
Bevacizumab
Inhibits angiogenesis
SE: Hypertension, delayed wound healing
EGFR inhibitors
Cetuximab/Panatumumab
Mechanism of resistance is downstream KRAS/BRAF mutations
Hence only use in wild-type KRAS
SE: Acneform rash, hypomag
Fluoropyrmidines
5-FU (IV) or capecitabine (oral pro-drug converted to fluorouracil in tumour)
SE:
Hand foot syndrome (Cape > 5FU)
Myelosuppression (5FU > Cape)
Oxaliplatin
Platinum derivative
Used in combo with fluoropyrmidines for CRC
SE:
Cumulative peripheral neuropathy
Cold sensitivity/dysthaesias
CRC poor prognostic factors
Right sided tumours
BRAF mutant (more common in right sided tumours)
Number of LN involved –> higher risk of recurrence
Stage 4 CRC with MMR or high MSI
Can use PDL1
