VP - Breast Cancer Flashcards
What risk factors may increase woman’s chance of developing Breast Cancer? (13) but try and list (8)
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
Diagnosis of breast cancer: (5 things)
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
The UK breast screening programme is for those over ___yrs old and is offered every _yrs.
50yrs
3yrs
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.
Breast, lobule and draining ducts
in ducts/lobules
in situ or non invasive
good
basement membrane
invasive
invasive
What does TNM stand for in TNM staging…
Tumour, Nodes, Metastases
Adverse prognostic factors for BC: (6)
- 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
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
Microscope Hormonal Tamoxifen Anastrozole Oestrogen Better Better
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.
Division Increased (high levels) Divide Division DNA
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.
Mastectomy
Auxiliary lymph
Lumpectomy
1cm
Conserves
Size and location
Cosmetic
Post
Radio and chemotherapy
Hormonal therapy
Herceptin (trastuzumab)
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
Lumpectomy Mastectomy 5cm 4 or over +ve lymph nodes Microdeposits outpatients
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 ______)
Oestrogen PR/ER 5yrs Oestrogen Neo Mastectomy
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.
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
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.
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
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
intermediate/high survival neo adjuvant to shrink tumour before surgery anthracycline pre menopausal, node +ve
An example of a chemotherapy based regime is ___100 consisting of ______, ______ and ______. It is given every __days for _ cycles.
FEC100 Flurouracil Epirubicin Cyclophosphamide 21days for 6 cycles
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 (_____)
Vomiting Suppression (nadir at 10 days) Infection risk Mucositis Mouthwash can help Arrhythmias Epirubicin Alopecia
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 ____)
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
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
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
Side effects of Herceptin: (6)
Nausea and vomiting Diarrhoea Rash Myalgia/arthralgia Infusion related reactions Cardiotoxicity - HF risk so ECHO scan before and after 4 months treatment
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?
HER2
Overexpressed (amplified)
HER2
EGF
1) Receptor degradation
2) Inhibition of angiogenesis
3) Recruits immune cells resulting in Antibody dependent cellular cytotoxicity
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.
Everolimus MTOR (mammaliam target of rapamycin) MTOR Serine threonine kinase MTOR Everolimus PR/ER +ve, HER2-ve Exemastane Hormonal
Everolimus side effects: (7)
Nausea and vomiting Stomatitis Decreased appetite Diarrhoea Fatigue Rash Infections
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)
Pertuzumab Monoclonal antibody that targets extracellular HER2 Ligand HER2 receptor Ligand Antibody dependent cellular cytotoxicity
Pertuzumab is licensed for __adjuvant treatment of early BC and ____ disease. Need HER2_ve status score of _ or more confirmed by ______________.
Neoadjuvant Metastatic \+ve 3 or more Immunohistochemistry
Pertuzumab is given with _____ (_____) and _____.
Pertuzumab is given as a loading dose and a _ weekly maintenance dose
Trastuzumab (Herceptin) and Docetaxel regimen
3 weekly
SE’s of Pertuzumab: (10)
- 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)
