Medical Oncology Flashcards
1
Q
What malignancy and manifestations is antibody Hu associated with?
A
Small cell lung cancer
Limbic encephalitis, peripheral neuropathy
2
Q
What malignancy and manifestations is antibody Yo associated with?
A
Breast / Ovarian Ca
Cerebellar degeneration
3
Q
What malignancy and manifestations is antibody Ri associated with?
A
Small cell lung cancer
Opsoclonus myoclonus, rhomboencephalitis
4
Q
What malignancy and manifestations is antibody Ma/Ta associated with?
A
Testicular cancer
Rhomboencephalitis
5
Q
Which malignancies is H Pylori associated with?
A
Gastric cancer
MALT lymphoma
Mechanism is chronic inflammation
6
Q
Which cancers is HPV implicated in?
A
Cervical cancer
Vulval cancer
Vaginal cancer
Penile cancer
Anal cancer
Oropharyngeal cancer
7
Q
Which genes are involved in the pathogenesis of Lynch syndrome?
A
MLH1
MSH2
MSH6
PMS2
EPCAM
MLH1 and PMS2 co-associated
MSH2 and MSH6 co-associated
8
Q
Name 5 different classes of chemotherapy.
A
Alkylating agents - e.g. platinum-based, mustard-based
Anti-metabolites - anti-folates, purine and pyramidine analogues
Alkaloids - microtubule and topoisomerase poisons
Antibiotics
Hormones
9
Q
Name 6 different alkylating agents.
A
Mustard and derivatives
- cyclosporin
- cyclophosphamide
- chlorambucil
- temozolamide
Platinum agents
- cisplatin
- carboplatin
- oxaliplatin
10
Q
What is the mechanism of action of alkylating chemotherapy agents?
A
Non-cell cycle specific
“Alkylates” guanine, distorting DNA structure; repair enzymes fail and fragment DNA
Cross-links DNA forming strong bond preventing helicase separating double strand, preventing replication
11
Q
Name 5 examples of anti-metabolite chemotherapy.
A
Purine antagonists (adenine, guanine)
- fludarabine
- 6MP
- methotrexate
Pyramidine antagonists (thymine, cytosine, uracil)
- 5FU
- gemcitabine
12
Q
Name 6 different alkylating agents.
A
Mustard and derivatives
- cyclosporin
- cyclophosphamide
- chlorambucil
- temozolamide
Platinum agents
- cisplatin
- carboplatin
- oxaliplatin
13
Q
Name 5 different classes of chemotherapy.
A
Alkylating agents - e.g. platinum-based, mustard-based
Anti-metabolites - anti-folates, purine and pyramidine analogues
Alkaloids - microtubule and topoisomerase poisons
Antibiotics
Hormones
14
Q
Name 5 examples of anti-metabolite chemotherapy.
A
Purine antagonists (adenine, guanine)
- fludarabine
- 6MP
- methotrexate
Pyramidine antagonists (thymine, cytosine, uracil)
- 5FU
- gemcitabine
15
Q
How do alkaloids work?
A
Vinca alkaloids - bind to tubulin and stop microtubule formation
Taxanes - bind to tubulin and stop microtubule disassembly
Topoisomerase inhibitor - DNA “tensioning” - S phase specific
16
Q
Name 7 examples of alkaloids.
A
Vinca alkaloids
- vincristine
- vinblastine
- vinorelbine
Taxanes
- paclitaxel
- docetaxel
Topoisomerase inhibitors
- Irinotecan
- etoposide
17
Q
Name 5 examples of antibiotic-based chemotherapies.
A
Doxorubicin
Daunorubicin
Epirubicin
Mitoxantrone
These are anthracyclines derived from streptomyces bacteria
18
Q
How do alkaloids work?
A
Vinca alkaloids - bind to tubulin and stop microtubule formation
Taxanes - bind to tubulin and stop microtubule disassembly
Topoisomerase inhibitor - DNA “tensioning” - S phase specific
19
Q
Name 7 examples of alkaloids.
A
Vinca alkaloids
- vincristine
- vinblastine
- vinorelbine
Taxanes
- paclitaxel
- docetaxel
Topoisomerase inhibitors
- Irinotecan
- etoposide
20
Q
Name 5 examples of antibiotic-based chemotherapies.
A
Doxorubicin
Daunorubicin
Epirubicin
Mitoxantrone
These are anthracyclines derived from streptomyces bacteria; non-cell cycle specific; interferes with topoisomerase 2
21
Q
How do anthracycline chemotherapies work?
A
Interferes with topoisomerase 2
Metabolite is a free radical causing widespread damage
Non-cell cycle specific
Induces histone eviction from chromatin
…definitely not to treat infections
22
Q
Name 6 classes of hormone-based chemotherapy.
A
LHRH analogues e.g. lucrin, Zoladex
Selective Oestrogen Receptor Modulator (SERM) e.g. tamoxifen
Aromatase inhibitors e.g. anastrozole, letrozole
Steroidal aromatase inhibitors e.g. exemestane
Peripheral androgen blockers e.g. bicalutamide, glutamine
Adrenal androgen synthesis e.g. abiraterone
23
Q
How does obesity impact upon the chance of developing pre-menopausal and post-menopausal breast cancer?
A
Obesity decreases the chance of developing pre-menopausal breast cancer
Obesity increases the chance of develop post-menopausal breast cancer
24
Q
Which gene is deleted in Familial Adenomatous Polyposis?
A
Deleted APC gene as germ-like mutation
25% have no family history
25
Which cancers may be seen in conjunction with FAP besides colorectal cancer?
Papillary thyroid
Ileal carcinoid
Gastric cancer
26
What is the Amsterdam criteria for Lynch syndrome?
“3-2-1 rule”
3 affected members
2 generations
1 under age 50
27
What features would suggest that a stage 2 colorectal cancer might be “high risk”? Name 4.
Obstruction
Poor differentiation
Extramural venous invasion
Adjacent organ invasion
28
What is the treatment for stage 2colorectal cancer?
Surgery cures 80% of cases
3-6 months adjuvant chemo for high risk stage 2 (5FU)
29
Which cancers may be seen in conjunction with FAP besides colorectal cancer?
Papillary thyroid
Ileal carcinoid
Gastric cancer
30
What is the Amsterdam criteria for Lynch syndrome?
“3-2-1 rule”
3 affected members
2 generations
1 under age 50
31
What features would suggest that a stage 2 colorectal cancer might be “high risk”? Name 4.
Obstruction
Poor differentiation
Extramural venous invasion
Adjacent organ invasion
32
What is the treatment for colorectal cancer?
Surgery
3-6 months adjuvant chemo for high risk stage 2 and stage 3
33
What is the treatment for colorectal cancer?
Surgery
3-6 months adjuvant chemo for high risk stage 2 and stage 3
34
What is the treatment for stage 3 colorectal cancer?
Stage 3, any T, N1/2 - surgery + 6 months adjuvant FOLFOX
T3/4 or node positive disease in rectal - XRT too (5FU is sensitiser)
If resectable mets - aim to cure
If unresectable - chemo (FOLFOX/FOLFIRI) + targeted therapy
35
What is bevacizumab, how does it work and what adverse effects does it have?
Mono Ab - binds and inhibits VEGF
Hypertension
Proteinuria
GI perforation
Thromboembolic events
Delayed wound healing
Can be used regardless of RAS/RAF status and location of tumour
36
What is bevacizumab, how does it work and what adverse effects does it have?
Mono Ab - binds and inhibits VEGF
Hypertension
Proteinuria
GI perforation
Thromboembolic events
Delayed wound healing
Can be used regardless of RAS/RAF status and location of tumour
37
What is cetuximab, how does it work and what are its side effects?
Mono Ab - anti-EGFR (EGFR -> RAS -> RAF -> MAPK)
Indicated in KRAS/RAF wild type (50% of CRC)
Rash (correlates with activity)
Skin sensitivity
Diarrhoea
Renal salt wasting
Worse toxicity in combination with capecitabine
38
What is cetuximab, how does it work and what are its side effects?
Mono Ab - anti-EGFR (EGFR -> RAS -> RAF -> MAPK)
Indicated in KRAS/RAF wild type (50% of CRC)
Rash (correlates with activity)
Skin sensitivity
Diarrhoea
Renal salt wasting
Worse toxicity in combination with capecitabine
39
What is trifluridine/tiperacil (Lonsurf)?
Nucleoside analogue and thymidine phosphorylase inhibitor
Works differently to 5-FU based fluoropyrimidines for CRC
SE - neutropenia
40
With GIST, what positive maker would you expect to see?
CD117 positive in 50% of cases (C-kit positive)
41
What sort of cells do you expect to see with GIST on histopath?
Spindle shaped cells
42
How are GISTs treated?
Imatinib
If PD - escalate doses (800mg daily max), then sunitinib and regorafenib
43
As well as a hypervascular liver lesion, what sort of AFP level would you expect to see in patients you suspect of HCC?
AFP >400
44
What is the main cause of HCC in Australia?
Viral hepatitis infection
45
What is the Barcelona Criteria for HCC and how does it influence treatment?
Stage 0 - single <2cm lesion, carcinoma in situ - resect/transplant
Stage A-B (multiple nodules, CPA or B) - chemoembolisation
Stage C - advanced(portal invasion) - TKIs
Stage D - terminal - (mets) - symptomatic
46
How is prostate Ca treated?
Organ confined - radical prostatectomy comparable to radical radiotherapy
Neo-adjuvant and adjuvant hormones for higher risk tumours treated with radiotherapy
47
What is the Barcelona Criteria for HCC and how does it influence treatment?
Stage 0 - single <2cm lesion, carcinoma in situ - resect/transplant
Stage A-B (multiple nodules, CPA or B) - chemoembolisation
Stage C - advanced(portal invasion) - TKIs
Stage D - terminal - (mets) - symptomatic
48
What is the main cause of HCC in Australia?
Viral hepatitis infection
49
As well as a hypervascular liver lesion, what sort of AFP level would you expect to see in patients you suspect of HCC?
AFP >400
50
How are GISTs treated?
Imatinib
If PD - escalate doses (800mg daily max), then sunitinib and regorafenib
51
What sort of cells do you expect to see with GIST on histopath?
Spindle shaped cells
52
With GIST, what positive maker would you expect to see?
CD117 positive in 50% of cases (C-kit positive)
53
How is prostate Ca treated?
Organ confined - radical prostatectomy comparable to radical radiotherapy
Neo-adjuvant and adjuvant hormones for higher risk tumours treated with radiotherapy
54
How is prostate Ca treated?
Organ confined - radical prostatectomy comparable to radical radiotherapy
Neo-adjuvant and adjuvant hormones for higher risk tumours treated with radiotherapy
55
In castrate-sensitive metastatic prostate cancer, patients with which symptoms benefit most from anti-androgen cover? Name 3 symptoms.
Extensive vertebral metastases
Risk of urinary retention
Poorly controlled pain
56
What is the treatment for metastatic castrate-resistant prostate cancer?
Chemo - docetaxel, cabazetaxel
Novel androgen receptor targeted therapies - abiraterone, enzalutamide
PARP inhibitors
Radiopharmaceuticals - radium-223, lutetium-PSMA
57
What is the treatment for metastatic castrate-resistant prostate cancer?
Chemo - docetaxel, cabazetaxel
Novel androgen receptor targeted therapies - abiraterone, enzalutamide
PARP inhibitors
Radiopharmaceuticals - radium-223, lutetium-PSMA
58
What are important toxicities with docetaxel? Name 3.
Sensory/motor PN
Neutropenic sepsis
Hypersensitivity reactions
59
What are important toxicities to consider with cabazitaxel? Name 4.
Diarrhoea
Cytopenias
Sensory/motor PN (less than docetaxel)
60
What are important toxicities to consider with abiraterone? Name 4.
Hypertension
Hypokalaemia
Peripheral oedema
Transaminitis
61
What are important toxicities to consider with enzalutamide? Name 3.
Hypertension
Fatigue
Contraindicated in seizures
62
What is sipuleucel T, and how is it used?
Patient’s own immune cells (APCs) used and combined with prostatic acid phosphates and GM-CSF fusion protein, before being returned to the patient
Used for metastatic castrate-resistant prostate cancer
Side effects are typically immune-based
63
What are the late effects of long term hormonal deprivation for prostate cancer therapy? Name 7.
Osteoporosis
Dyslipidaemia
Weight gain
BMD
Mood
Insulin resistance
CVS morbidity / mortality
64
What is the significant side effect of V600E inhibitors such as vemurafenib?
Hand-foot syndrome
65
How do the presence of brain mets impact upon melanoma treatment?
1-3 mets - stereotactic surgery (SRS) or surgery
>3 mets - BRAF inhibitors or immunotherapy
66
Name 6 indications for BRCA testing in breast Ca.
<40 years old
“Triple negative” pathology <50 years
Bilateral breast Ca, one <50 years
Male breast cancer
Jewish ancestry
Family history of ovarian cancer
67
Name 3 indications for BRCA testing in ovarian Ca.
<70 years
Jewish ancestry
Family history of breast or ovarian cancer
68
What should be offered to patients carrying BRCA mutations? Name 3 things for breast Ca, and one for ovarian Ca.
Breast
- offer bilateral mastectomy (best age <40)
- offer risk-reducing salpingo-oophorectomy (not useful for BRCA1; most are ER/PR -ve)
- offer screening - annual MRI/MG from age 30 (MG only from 50)
Ovarian
- RRSO once family complete or <35 (BRCA1), <45 (BRCA2)
No evidence for screening benefit
69
How do PARP inhibitors work?
Cell death via synthetic lethality
PARP1 is responsible for base-excision repair. BRCA is responsible for homologous recombination, another mechanism for DNA repair. However, homologous recombination does not occur with a BRCA mutation in place. With both PARP1 and BRCA pathways not intact, no DNA repair occurs, resulting in cell death.
70
What are side effects of PARP inhibitors? Name 4.
Nausea
Diarrhoea
Fatigue
Abdominal pain
71
How does sentinel node biopsy help inform treatment plans for breast Ca?
Negative sentinel node (70% of patients) - better prognosis overall and no further surgery required
1-2 sentinel nodes involved with cancer - no benefit for axillary dissection noting most get radiotherapy to breast
>2 sentinel nodes - axillary dissection improves local control
72
What chemotherapy agents are typically used for breast cancer?
Anthracycline (doxorubicin, epirubicin) best in meta-analyses
Addition of taxane (paclitaxel, docetaxel) improves on anthracycline alone
2 weekly dose dense chemotherapy better than 3 weekly
Concurrent trastuzumab (Herceptin) in HER2 positive improves disease free survival and survival; standard treatment duration one year
73
How does alcohol impact upon chemotherapy-induced emesis?
High ETOH is protective
74
For women with ER +ve breast Ca, how is risk stratified via Oncotype Dx?
RS <11 - 1% chance of recurrence at 5 years with endocrine treatment alone
RS 11-25 - no benefit from addition of chemotherapy to endocrine treatment
RS >25 - chemo + hormonal therapy
75
What are side effects of tamoxifen? Name 2.
Increased DVT/PE
Increased risk of uterine cancer
76
Describe the interaction between SSRIs and tamoxifen.
Blocking of CYP2D6 reduces active tamoxifen metabolites by SSRI - avoid concurrent fluoxetine or paroxetine
77
Name 3 side effects of aromatase inhibitors.
Menopausal symptoms
Arthralgia
Accelerated osteoporosis
78
How does fulvestrant work, for whom is it indicated, and what is the major side effect?
ER destroyer
For metastatic breast Ca in post-menopausal women
Hepatoxicity
79
What are palbociclib/ribociclib, when can they be used and what is the major side effect?
CDK4/6 inhibitor
Metastatic breast Ca in combination with aromatase inhibitor or fulvestrant
Neutropaenia
80
What is everolimus, and when can it be used in breast Ca?
mTOR inhibitor
Metastatic breast Ca combined with exemestane
81
Name 3 side effects associated with everolimus
Stomatitis
Rash
Fatigue
82
Name 4 different HER2/3 target drugs.
Trastuzumab - HER2
Pertuzumab - targets HER2 and HER3 hetero-dimerisation
Lapatinib - oral anti-HER2 agent
T-DM1 - antibody drug conjugate
83
Which tumour markers are associated with seminomas and non-seminomas respectively?
Seminomas - bHCG (half-life 5-7 days)
Non-seminomas - AFP (half-life 18-36 hours)
AFP is NEVER seminoma
84
Name 4 risk factors for testicular cancer.
Siblings with testicular Ca (6-10x risk)
Crypto-orchidism
Klinefelter’s
Atrophy
85
What is the treatment for stage I (confined to testicle) seminomas following orchidectomy?
Option 1 - surveillance
Option 2 - 1 x carboplatin
86
What is the treatment for stage 1 (confined to testicle) non-seminoma?
Option 1 - surveillance
Option 2 - 1 x BEP
87
What is the standard chemotherapy regimen for metastatic testicular cancer?
BEP (bleomycin, etoposide, cisplatin) for 3-4 cycles
Surgical resection of residual disease in non-seminomas
88
Name 3 side effects associated with cisplatin.
Ototoxicity - dose-related, tinnitus; permanent high frequency hearing loss
Nephrotoxicity - average 15% decline in GFR in testicular patients treated with BEP
Neurotoxicity - peripheral (sensory) neuropathy, usually resolves in 6-12 months (may be permanent)
89
What types of chemotherapies are more likely to predispose patients to secondary malignancies?
Alkylating agents e.g. cyclophosphamide
90
What material predisposes to the development of mesotheliomas?
Blue asbestos (crocidolite)
91
What treatments are available for mesotheliomas?
Palliative chemotherapy with cisplatin and pemetrexed
Chemo toxicity can be reduced by concurrent treatment with B12 and folic acid
Some ICI activity in mesothelioma second-line
92
How are NSCLCs treated per stage in general terms?
Stage I and II
- surgery where patient is fit (radical, or SABR if not fit for surgery)
- adjuvant chemotherapy for resected stage II (hilar nodes involved)
Stage IIIA (ipsilateral mediastinal nodes involved) - radical combination radiotherapy + chemotherapy +/- surgery
Stage IIIB (contralateral mediastinal nodes involved) - palliative chemotherapy and/or radiotherapy
Stage IV (metastatic) - palliative chemotherapy and/or radiotherapy
93
What cancer would cancer cells staining for TTF1 suggest?
Adenocarcinoma
94
Name 3 factors that might suggest an EGFR mutation in an adenocarcinoma.
Female
Asian
Non-smoker
95
What sort of chemotherapies can be considered for palliative NSCLC?
Platinum drug + paclitaxel or gemcitabine or vinorelbine
Adenocarcinomas may do better with pemetrexed combined with platinum
96
In all lung cancers, name 2 factors where PD-L1 expression might be higher.
Males
Smokers
97
Name 4 targets for targeted therapies in lung adenocarcinomas.
EGFR mutation
ALK translocation
ROS1 re-arrangement
BRAF mutation
98
Name 3 drugs that can be used as targeted therapies in patients with lung adenocarcinoma with an EGFR mutation.
Erlotinib
Gefitinib
Afatinib
99
Name 2 drugs that can be used in lung adenocarcinoma with an ALK translocation.
Crizotinib
Alectinib
Alectinib has a better response rate (including CNS mets) and disease control at 12 months with lower toxicity than crizotinib
100
Name a drug that can be used in lung adenocarcinoma patients with ROS1 rearrangement.
Crizotinib
101
Name a drug combination that can be used in lung adenocarcinoma patients with a BRAF mutation.
Trametinib/dabrafenib
102
What are the 6 grades of ECOG?
0 - fully active, able to carry on all predispose activities without restriction
1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g. light housework or office work)
2 - Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours
3 - Capable of only limited self-care; confined to bed or chair more than 50% of waking hours
4 - Completely disabled and not capable of self-care; totally confined to bed or chair
5 - Dead
103
What is sipuleucel T, and how is it used?
Patient’s own immune cells (APCs) used and combined with prostatic acid phosphates and GM-CSF fusion protein, before being returned to the patient
Used for metastatic castrate-resistant prostate cancer
Side effects are typically immune-based
104
What are the late effects of long term hormonal deprivation for prostate cancer therapy? Name 7.
Osteoporosis
Dyslipidaemia
Weight gain
BMD
Mood
Insulin resistance
CVS morbidity / mortality
105
What is the significant side effect of V600E inhibitors such as vemurafenib?
Hand-foot syndrome
106
How do the presence of brain mets impact upon melanoma treatment?
1-3 mets - stereotactic surgery (SRS) or surgery
>3 mets - BRAF inhibitors or immunotherapy
107
Name 6 indications for BRCA testing in breast Ca.
<40 years old
“Triple negative” pathology <50 years
Bilateral breast Ca, one <50 years
Male breast cancer
Jewish ancestry
Family history of ovarian cancer
108
Name 3 indications for BRCA testing in ovarian Ca.
<70 years
Jewish ancestry
Family history of breast or ovarian cancer
109
What should be offered to patients carrying BRCA mutations? Name 3 things for breast Ca, and one for ovarian Ca.
Breast
- offer bilateral mastectomy (best age <40)
- offer risk-reducing salpingo-oophorectomy (not useful for BRCA1; most are ER/PR -ve)
- offer screening - annual MRI/MG from age 30 (MG only from 50)
Ovarian
- RRSO once family complete or <35 (BRCA1), <45 (BRCA2)
No evidence for screening benefit
110
How do PARP inhibitors work?
Cell death via synthetic lethality
PARP1 is responsible for base-excision repair. BRCA is responsible for homologous recombination, another mechanism for DNA repair. However, homologous recombination does not occur with a BRCA mutation in place. With both PARP1 and BRCA pathways not intact, no DNA repair occurs, resulting in cell death.
111
What are side effects of PARP inhibitors? Name 4.
Nausea
Diarrhoea
Fatigue
Abdominal pain
112
How does sentinel node biopsy help inform treatment plans for breast Ca?
Negative sentinel node (70% of patients) - better prognosis overall and no further surgery required
1-2 sentinel nodes involved with cancer - no benefit for axillary dissection noting most get radiotherapy to breast
>2 sentinel nodes - axillary dissection improves local control
113
What chemotherapy agents are typically used for breast cancer?
Anthracycline (doxorubicin, epirubicin) best in meta-analyses
Addition of taxane (paclitaxel, docetaxel) improves on anthracycline alone
2 weekly dose dense chemotherapy better than 3 weekly
Concurrent trastuzumab (Herceptin) in HER2 positive improves disease free survival and survival; standard treatment duration one year
114
How does alcohol impact upon chemotherapy-induced emesis?
High ETOH is protective
115
For women with ER +ve breast Ca, how is risk stratified via Oncotype Dx?
RS <11 - 1% chance of recurrence at 5 years with endocrine treatment alone
RS 11-25 - no benefit from addition of chemotherapy to endocrine treatment
RS >25 - chemo + hormonal therapy
116
What are side effects of tamoxifen? Name 2.
Increased DVT/PE
Increased risk of uterine cancer
117
Describe the interaction between SSRIs and tamoxifen.
Blocking of CYP2D6 reduces active tamoxifen metabolites by SSRI - avoid concurrent fluoxetine or paroxetine
118
Name 3 side effects of aromatase inhibitors.
Menopausal symptoms
Arthralgia
Accelerated osteoporosis
119
What is sipuleucel T, and how is it used?
Patient’s own immune cells (APCs) used and combined with prostatic acid phosphates and GM-CSF fusion protein, before being returned to the patient
Used for metastatic castrate-resistant prostate cancer
Side effects are typically immune-based
120
What are the late effects of long term hormonal deprivation for prostate cancer therapy? Name 7.
Osteoporosis
Dyslipidaemia
Weight gain
BMD
Mood
Insulin resistance
CVS morbidity / mortality
121
What is the significant side effect of V600E inhibitors such as vemurafenib?
Hand-foot syndrome
122
How do the presence of brain mets impact upon melanoma treatment?
1-3 mets - stereotactic surgery (SRS) or surgery
>3 mets - BRAF inhibitors or immunotherapy
123
Name 6 indications for BRCA testing in breast Ca.
<40 years old
“Triple negative” pathology <50 years
Bilateral breast Ca, one <50 years
Male breast cancer
Jewish ancestry
Family history of ovarian cancer
124
Name 3 indications for BRCA testing in ovarian Ca.
<70 years
Jewish ancestry
Family history of breast or ovarian cancer
125
What should be offered to patients carrying BRCA mutations? Name 3 things for breast Ca, and one for ovarian Ca.
Breast
- offer bilateral mastectomy (best age <40)
- offer risk-reducing salpingo-oophorectomy (not useful for BRCA1; most are ER/PR -ve)
- offer screening - annual MRI/MG from age 30 (MG only from 50)
Ovarian
- RRSO once family complete or <35 (BRCA1), <45 (BRCA2)
No evidence for screening benefit
126
How do PARP inhibitors work?
Cell death via synthetic lethality
PARP1 is responsible for base-excision repair. BRCA is responsible for homologous recombination, another mechanism for DNA repair. However, homologous recombination does not occur with a BRCA mutation in place. With both PARP1 and BRCA pathways not intact, no DNA repair occurs, resulting in cell death.
127
What are side effects of PARP inhibitors? Name 4.
Nausea
Diarrhoea
Fatigue
Abdominal pain
128
How does sentinel node biopsy help inform treatment plans for breast Ca?
Negative sentinel node (70% of patients) - better prognosis overall and no further surgery required
1-2 sentinel nodes involved with cancer - no benefit for axillary dissection noting most get radiotherapy to breast
>2 sentinel nodes - axillary dissection improves local control
129
What chemotherapy agents are typically used for breast cancer?
Anthracycline (doxorubicin, epirubicin) best in meta-analyses
Addition of taxane (paclitaxel, docetaxel) improves on anthracycline alone
2 weekly dose dense chemotherapy better than 3 weekly
Concurrent trastuzumab (Herceptin) in HER2 positive improves disease free survival and survival; standard treatment duration one year
130
How does alcohol impact upon chemotherapy-induced emesis?
High ETOH is protective
131
For women with ER +ve breast Ca, how is risk stratified via Oncotype Dx?
RS <11 - 1% chance of recurrence at 5 years with endocrine treatment alone
RS 11-25 - no benefit from addition of chemotherapy to endocrine treatment
RS >25 - chemo + hormonal therapy
132
What are side effects of tamoxifen? Name 2.
Increased DVT/PE
Increased risk of uterine cancer
133
Describe the interaction between SSRIs and tamoxifen.
Blocking of CYP2D6 reduces active tamoxifen metabolites by SSRI - avoid concurrent fluoxetine or paroxetine
134
Name 3 side effects of aromatase inhibitors.
Menopausal symptoms
Arthralgia
Accelerated osteoporosis
135
What is sipuleucel T, and how is it used?
Patient’s own immune cells (APCs) used and combined with prostatic acid phosphates and GM-CSF fusion protein, before being returned to the patient
Used for metastatic castrate-resistant prostate cancer
Side effects are typically immune-based
136
What are the late effects of long term hormonal deprivation for prostate cancer therapy? Name 7.
Osteoporosis
Dyslipidaemia
Weight gain
BMD
Mood
Insulin resistance
CVS morbidity / mortality
137
What is the significant side effect of V600E inhibitors such as vemurafenib?
Hand-foot syndrome
138
How do the presence of brain mets impact upon melanoma treatment?
1-3 mets - stereotactic surgery (SRS) or surgery
>3 mets - BRAF inhibitors or immunotherapy
139
Name 6 indications for BRCA testing in breast Ca.
<40 years old
“Triple negative” pathology <50 years
Bilateral breast Ca, one <50 years
Male breast cancer
Jewish ancestry
Family history of ovarian cancer
140
Name 3 indications for BRCA testing in ovarian Ca.
<70 years
Jewish ancestry
Family history of breast or ovarian cancer
141
What should be offered to patients carrying BRCA mutations? Name 3 things for breast Ca, and one for ovarian Ca.
Breast
- offer bilateral mastectomy (best age <40)
- offer risk-reducing salpingo-oophorectomy (not useful for BRCA1; most are ER/PR -ve)
- offer screening - annual MRI/MG from age 30 (MG only from 50)
Ovarian
- RRSO once family complete or <35 (BRCA1), <45 (BRCA2)
No evidence for screening benefit
142
How do PARP inhibitors work?
Cell death via synthetic lethality
PARP1 is responsible for base-excision repair. BRCA is responsible for homologous recombination, another mechanism for DNA repair. However, homologous recombination does not occur with a BRCA mutation in place. With both PARP1 and BRCA pathways not intact, no DNA repair occurs, resulting in cell death.
143
What are side effects of PARP inhibitors? Name 4.
Nausea
Diarrhoea
Fatigue
Abdominal pain
144
How does sentinel node biopsy help inform treatment plans for breast Ca?
Negative sentinel node (70% of patients) - better prognosis overall and no further surgery required
1-2 sentinel nodes involved with cancer - no benefit for axillary dissection noting most get radiotherapy to breast
>2 sentinel nodes - axillary dissection improves local control
145
What chemotherapy agents are typically used for breast cancer?
Anthracycline (doxorubicin, epirubicin) best in meta-analyses
Addition of taxane (paclitaxel, docetaxel) improves on anthracycline alone
2 weekly dose dense chemotherapy better than 3 weekly
Concurrent trastuzumab (Herceptin) in HER2 positive improves disease free survival and survival; standard treatment duration one year
146
How does alcohol impact upon chemotherapy-induced emesis?
High ETOH is protective
147
For women with ER +ve breast Ca, how is risk stratified via Oncotype Dx?
RS <11 - 1% chance of recurrence at 5 years with endocrine treatment alone
RS 11-25 - no benefit from addition of chemotherapy to endocrine treatment
RS >25 - chemo + hormonal therapy
148
What are side effects of tamoxifen? Name 2.
Increased DVT/PE
Increased risk of uterine cancer
149
Describe the interaction between SSRIs and tamoxifen.
Blocking of CYP2D6 reduces active tamoxifen metabolites by SSRI - avoid concurrent fluoxetine or paroxetine
150
Name 3 side effects of aromatase inhibitors.
Menopausal symptoms
Arthralgia
Accelerated osteoporosis
