VP - Breast Cancer Flashcards

1
Q

What risk factors may increase woman’s chance of developing Breast Cancer? (13) but try and list (8)

A

1) Age (doubles each year until menopause)
2) Geographical location (higher risk UK than Asia)
3) Age of menarche (before 12 = risk factor)
4) Age of menopause - >55 and risk as more oestrogen
5) Pregnancy - before 25 and protective - over 30 = risk
6) Lactation - BF for >6 months = protective
7) Radiation exposure = risk
8) Weight - increased weight = risk
9) Oral contraceptive - use for >4yrs

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2
Q

Diagnosis of breast cancer: (5 things)

A

1) History
Lump/thickening in breast, breast pain, nipple discharge, symptoms from metastases e.g. bone pain, SOB
2) Exam
Skin dimpling, lymph nodes (enlarged as often spread here)
3) Mammography
x show up in 10-15% cases as some cancers absorb x-ray
4) Breast ultrasound
Tells us if solid tumour or cystic fluid filled lump (often benign)
5) Fine needle aspirate/biopsy
sample of lump taken and analysed for malignant cells

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3
Q

The UK breast screening programme is for those over ___yrs old and is offered every _yrs.

A

50yrs

3yrs

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4
Q

Pathology:
Cancer develops from cells that line the ____, ____ and ____ ducts

Cancer that remains in ___/____ is referred to as __ ____ or ___ _____. If diagnosed at this stage then it is a ____ prognosis.

Cancer that has spread to the _____ _____ and surrounding tissue is referred to as _____. It is different from metastatic breast cancer and most cancers are _____ at the point of diagnosis.

A

Breast, lobule and draining ducts

in ducts/lobules
in situ or non invasive
good

basement membrane
invasive
invasive

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5
Q

What does TNM stand for in TNM staging…

A

Tumour, Nodes, Metastases

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6
Q

Adverse prognostic factors for BC: (6)

A
  • Higher TNM staging
  • Poorly differentiated cells - if they look different to normal tissue then poorer prognosis
  • Lymph/vascular invasion
  • Oestrogen receptor/progesterone receptor -ve = poorer prognosis
  • HER2+ - can use Herceptin but more aggressive cancer and grows quicker
  • Age - less than 34yrs = <50% 5 year survival - most relapse within 3 years
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7
Q

Oestrogen receptors (ER) concentration is measured when tumours are examined under _____.
ER concentration predicts response to _____ therapy with drugs e.g. _____ and _____ that deprive the body of _____.
ER +ve breast cancer has a ____ prognosis
Progesterone receptor (PR) is also a prognostic indicator. PR +ve breast cancer has a ____ prognosis

A
Microscope 
Hormonal 
Tamoxifen 
Anastrozole
Oestrogen 
Better 
Better
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8
Q

Oestrogen binds the ER. When bound, signals are sent to stimulate cell ___ which can lead to cancer growth. _____ oestrogen is a risk factor for breast cancer. When cells are stimulated to ____ at a high ____ rate there is less time for ___ repair to occur so errors and mutations accumulate.

A
Division 
Increased (high levels) 
Divide 
Division 
DNA
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9
Q

Surgery in breast cancer:
1) _______: involves total removal of breast including: areola, _____ ____ nodes, skin and nipple

2) ______: involves removing the lump and at least a _cm margin of normal tissue around to (____ the breast)

Choice of procedure depends on the ___ and ____ of the tumour and the desired _____ outcome.

Adjuvant therapy (____ surgery) is often used e.g. ___ and ___ therapy and ____ therapy or _____ or a combination of these.

A

Mastectomy
Auxiliary lymph

Lumpectomy
1cm
Conserves

Size and location
Cosmetic

Post
Radio and chemotherapy
Hormonal therapy
Herceptin (trastuzumab)

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10
Q

Radiotherapy:

  • High energy radiation used to eradicate BC cells
  • All patients who have had a wide local excision (_____) and those who have had a _____ and those at risk of recurrence e.g. tumour >_cm or _or over +ve ____ nodes) are offered it
  • It reduces the risk of relapse and improves overall survival as it eradicates ______ of cancer cells
  • Patients are __patients and are in hospital for about 10 minutes for 5 days for around 3-5 weeks
  • Most patients have radiotherapy
A
Lumpectomy 
Mastectomy 
5cm 
4 or over +ve lymph nodes 
Microdeposits 
outpatients
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11
Q

Hormonal therapies: Aims to remove ____ that drives cell growth.
Given to all patients with __/__ +ve tumours.
Given for _ years after surgery (some on for 15yrs)
Sensitive cancer cells need ____ to stay alive so depleting it helps to control/kill the hormone sensitive BC cells.
These therapies are also used as ___ adjuvant therapies (before surgery) to shrink large tumours and facilitate breast conserving surgery (prevent needing ______)

A
Oestrogen 
PR/ER
5yrs
Oestrogen 
Neo 
Mastectomy
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12
Q

Tamoxifen is an ____ antagonist that acts on _____ receptor.
It prevents ____ from binding so prevents ____ dependent ____ transcription. It enters the cells by _____ diffusion and binds the ____ receptor. This then binds ___ but adopts a different conformation that prevents recruitment of _____ e.g. SRC and D1.

Tamoxifen reduces the risk of reoccurrence by around __%, reduces the risk of mortality and ____ BC development. It is generally well tolerated BUT _____ side effects e.g. 4 things… LIST THEM
This can lead to compliance issues as patients feel well but experience side effects so want to stop taking drug.

A
Oestrogen 
Oestrogen 
Oestrogen 
Oestrogen 
Gene 
Passive 
Oestrogen 
DNA 
Co-factors 

50%
Conlateral
Menopausal
e.g. hot flushes, sweats , weight gain and increased risk of endometrial cancer

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13
Q

Aromatase inhibitors: e.g. _____, l___ and e______.
These block conversion of ____ from adrenal ____ to ____ in peripheral tissues by inhibiting _____ enzyme. This is only effective in ____ _____ women as pre ______ produce oestrogen from _____.
_____ = agent of choice in ___ ____ women as stated by the ATAC trial which compared treatment to that with Tamoxifen. Prolonged disease free survival and less adverse effects.

Side effects: reduced ___ _____ density so all patients have a ____ _____ scan when treatment is initiated as they are at increased risk of ____ and ______. This scan happens roughly every ____. Also ____ side effects too.

A
Anastrozole, letrozole and exemastane 
Androgens
Cortex 
Oestrogen 
Aromatase 
Post menopausal women 
Menopausal 
Ovaries 
Anastrozole 
Post menopausal women 
Reduced bone mineral density 
Bone density 
Fractures and osteoporosis 
Year
Menopausal
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14
Q

Chemotherapy - adjuvant post surgery

  • adjuvant for those at _____/___ risk of recurrence
  • adjuvant chemo increases absolute ____ benefit depending on pt and tumour characteristics
  • also used as a __ adjuvant before surgery to ____ the tumour
  • ____ drug regimes are often used
  • _____ based regimes are more effective according to a ____ review
  • Also most effective in ___ menopausal, node _-ve patients
  • Variations in regimen between hospitals
A
intermediate/high 
survival 
neo adjuvant to shrink tumour before surgery 
anthracycline 
pre menopausal, node +ve
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15
Q

An example of a chemotherapy based regime is ___100 consisting of ______, ______ and ______. It is given every __days for _ cycles.

A
FEC100
Flurouracil 
Epirubicin 
Cyclophosphamide 
21days for 6 cycles
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16
Q

Side effects of the FEC100 regimen include:

  • Nausea and ____
  • Bone marrow ____ (____ at __ days) - WCC low so ___ risk
  • _____ - soreness and inflam of GIT from mouth to anus - can RX ___ to help with this
  • Cardiac _____ and cardiomyopathy (espesh with _____)
  • Loss of hair (_____)
A
Vomiting 
Suppression (nadir at 10 days) 
Infection risk 
Mucositis 
Mouthwash can help 
Arrhythmias 
Epirubicin 
Alopecia
17
Q

Pharmaceutical care issues with FEC:

  • Check ___ and dose - chemo dose based on ___
  • Check ___ as chemo can drop ___ count
  • Check ___ function as cyclophosphamide is ____ excreted
  • Check ___ (may need to decrease epirubicin and flurouracil dose if deranged)
  • Ensure _____ rx and dispensed - take day ___ chemo
  • Monitor cumulative dose of _____ as heart issues and it has a maximum _____ exposure limit - HF risk
  • Older patients may need an ____ scan prior to chemo and caution in cardiac disease
  • Ensure pt vigilant for signs and symptoms of _____ as risk of _____ sepsis (WCC low and ____ low so pick up ____)
A
BSA, BSA
FBC, WCC
Renal, really 
LFTs
Antiemetics, before 
Epirubicin, lifetime exposure 
ECHO 
Infection as risk of neutropenic sepsis 
neutrophils low so pick up infections
18
Q

Targeted therapy e.g ____ (______)

  • Recombinant _____ _____ ______ which targets the ____ protein
  • Approx __% patents _____ ____ = poor prognosis
  • If ___ ______ of 3+ or greater then benefit from _____ (can stain under microscope to see if ____+ve)
  • NICE approved for _____ BC and early stage BC
  • Given every _ weeks for _ year SC
A
Trastuzumab (Herceptin)
Recombinant humanised monoclonal antibody 
Targets the HER2 protein 
20% pts overexpress HER2
HER2 over expression 
Trastuzumab (Herceptin)
Stain under micro to see if HER2+VE
Approved for metastatic
3 weeks for 1 year
19
Q

Side effects of Herceptin: (6)

A
Nausea and vomiting
Diarrhoea 
Rash 
Myalgia/arthralgia
Infusion related reactions 
Cardiotoxicity - HF risk so ECHO scan before and after 4 months treatment
20
Q

MOA of Herceptin (Trastuzumab)

  • Monoclonal antibody targets the _____ receptor which is _____ in breast cancer
  • Binds the _____ receptor and prevents ____ binding
  • This reduces cell growth

It also causes 3 things. What are they?

A

HER2
Overexpressed (amplified)
HER2
EGF

1) Receptor degradation
2) Inhibition of angiogenesis
3) Recruits immune cells resulting in Antibody dependent cellular cytotoxicity

21
Q

New therapies in Breast Cancer: _____ (Afinitor)

  • a selective _____ (_____ target of _____) inhibitor that is often hyper activated in BC
  • ____ is a key ____ threonine ____ that plays a role in proliferation and apoptosis
  • ____ is often unregulated in BC hence if you inhibit it, a reduction in cell proliferation occurs
  • _____ is licensed for treatment of ER/PR v_e HER2 _ve advanced BC in combination with _____ in postmenopausal women after progression after ______ treatment.
A
Everolimus 
MTOR (mammaliam target of rapamycin) 
MTOR 
Serine threonine kinase 
MTOR 
Everolimus
PR/ER +ve, HER2-ve
Exemastane 
Hormonal
22
Q

Everolimus side effects: (7)

A
Nausea and vomiting
Stomatitis
Decreased appetite 
Diarrhoea
Fatigue
Rash
Infections
23
Q

Newer therapies - P______ IV infusion

  • A _____ antibody that targets _______ dimerisation domain of the ____ receptor.
  • It blocks ____ dependent heterodimerisation of ____ and hence inhibits ____ initiated intracellular signalling through MAPK and PI3K. Inhibiting these pathways inhibits cell growth arrest. It also causes ______ _____ _____ _____ (ADCC)
A
Pertuzumab
Monoclonal antibody that targets extracellular
HER2
Ligand 
HER2 receptor 
Ligand 
Antibody dependent cellular cytotoxicity
24
Q

Pertuzumab is licensed for __adjuvant treatment of early BC and ____ disease. Need HER2_ve status score of _ or more confirmed by ______________.

A
Neoadjuvant 
Metastatic 
\+ve 
3 or more
Immunohistochemistry
25
Q

Pertuzumab is given with _____ (_____) and _____.

Pertuzumab is given as a loading dose and a _ weekly maintenance dose

A

Trastuzumab (Herceptin) and Docetaxel regimen

3 weekly

26
Q

SE’s of Pertuzumab: (10)

A
  • Allopecia
  • Headache
  • Nausea, vomiting, diarrhoea
  • Mucostitis
  • Rash
  • Infusion related reactions (monitor for 60mins after 1st infusion)
  • RTIs
  • Infections (immunosuppression) - neutropenia
  • Cardiotoxicity - left ventricular dysfunction (congestive HF) so assess LVEF prior to administration and every 3 weeks if metastatic and 2 weeks for neoadjuvant therapy)