Breast cancer Flashcards
What % of all malignancies are breast cancer?
20%
Incidence of breast cancer is increasing by what % each year?
1%
What is the lifetime risk of breast cancer for women in the UK?
1 in 9
How many people are diagnosed with breast cancer in the UK each year?
41,000
How many breast cancer deaths are there per year in the UK?
13,000
How many cases of male breast cancer are there in the UK per year?
300
Compared to the rest of the world, what are the mortality rates in the UK like?
One of the highest mortality rates in the world
What are the risk factors for breast cancer? (9)
- Age
- Geography
- Age at menarche (early) and menopause (late - after age 55 then risk doubles)
- Age at first pregnancy (late or nulliparity)
- Family history
- Exogenous oestrogens
- Diet (high fat intake, obesity and alcohol)
- Benign breast disease
- Radiation
What % of female breast cancer is due to inheritance of the mutated copy of BRCA 1 or 2?
5-10%
What % risk is posed to women with the mutated BRCA 1 or 2, by the age of 70 years?
87%
Which other genes are associated with contributing to familial breast cancer? (3)
- PTEN (Cowden disease)
- MSH1 or 2 (HNPCC)
- p53 (Li-Fraumeni syndrome)
What may be offered to women who are asymptomatic but who have a high risk of developing breast cancer due to inheritance of a mutated gene? (3)
- Prophylactic surgery (can reduce risk of breast cancer by 95%)
- Screening - MRI in women under 50 who are high risk, as mammography would not be useful
- Breast cancer-prevention trials - clinical trials used tamoxifen
In which breast is cancer more common?
Breast cancer is more common in the left breast
50% of breast cancers arise in which quadrant?
Upper outer quadrant
What is the commonest pathology for breast cancer?
Ductal carcinoma
What does DCIS mean?
Ductal carcinoma in situ
What % of breast carcinomas arise in the ducts?
90%
How does DCIS begin?
An atypical proliferation of ductal epithelium that eventually fills and plugs the ducts with neoplastic cells
How is the DCIS remain as such, as opposed to an invasive ductal carcinoma?
It is classified as a DCIS as long as the tumour remains within the confines of the ductal basement membrane
What % of DCIS will progress to invasive?
30-50%
How does DCIS appear on mammography?
An area of micro-calcification
What risk do lobular carcinoma in-situ carry?
They carry the risk of ipsilateral and contralateral invasion and typically they are not palpable nor contain micro-calcification
What % of breast cancers are invasive ductal carcinomas?
75%
What do the malignant cells of invasive ductal carcinoma (IDC) consist of?
Fibrous stroma (these can be dense, and then known as scirrhous carcinoma)
Where does the IDC tumour invade to?
Through the breast tissue into the lymphatics and vascular spaces, to gain access to regional nodes and the systemic circulation
What are the ‘sentinel’ or regional nodes associated with breast cancer?
Axillary (and less often internal mammary)
To which organs is breast cancer most likely to spread? (6)
- Bone
- Lung
- Pleura
- Liver
- Skin
- CNS
Which three features of the tumour are assessed to give a histological grade (I - III)?
- Tubule formation
- Nuclear pleomorphism
- Mitotic frequency
Immunocytochemistry commonly assess which two hormone receptor statuses in IDC?
Oestrogen and progesterone receptor status
If the breast cancer expresses the nuclear oestrogen receptor (ER), what does this mean in terms of prognosis?
It conveys a better prognosis, compared to ER-negative tumours
What % of breast cancers are ER-positive?
60-70%
What does ER-negative (oestrogen receptor status), relate to in terms of prognosis?
Not such a good prognosis as there is a higher risk of spread to lymph nodes and distant sites at presentation
Which other biological marker is used to predict prognosis and guide therapy?
HER2 - growth factor receptor gene
How is HER2 assessed?
By either immunocytochemistry or fluorescence in situ hybridisation (FISH)
What is HER2 associated with?
Aggressive behaviour, high risk lymph node involvement and haematogenous spread
What does triple negative breast cancer refer to?
These tumours do not express ER, PR (progesterone receptor) or HER2.
What % of breast cancers are triple negative?
15%
In which women is triple negative breast cancer more likely to occur?
Pre-menopausal women and in association with BRCA 1
What do triple negative breast cancers express?
Epidermal growth factor receptor (EGFR)
What are the subtypes of invasive ductal carcinoma? (5)
- Medullary carcinoma
- Mucinous carcinoma
- Tubular carcinoma
- No specific type
- Paget’s disease
Paget’s disease of the breast is ductal carcinoma with involvement of which other areas?
The skin of the nipple and areola
Which other forms of breast cancer are there in addition to invasive ductal carcinoma (IDC)
- Invasive lobular carcinoma
- Mixed lobular and ductal carcinoma
- Sarcoma
- Lymphoma
- Metastases (secondary)
What are the prognostic factors which determine survival after a diagnosis of breast cancer? (8)
- Tumour size
- No. of histologically positive axillary lymph nodes
- Tumour grade
- these are combined in the Nottingham Prognostic Index (NPI) - Hormone receptor status (ER and PR)
- HER2
- Histological subtype
- Lymphovascular invasion
- Proliferative index
What is the equation to calculate the Nottingham prognostic index?
NPI = (0.2 x pathological tumour size cm + grade (1-3) + axillary node score)
How are the axillary node scores assigned?
1 = no lymph node positive 2 = 1-3 lymph nodes positive 3 = >3 lymph nodes positive
How are the NPI scores ranked/classified?
Prognosis:
Good = <3.41
Intermediate = 3.41 - 5.4
Poor = >5.4
7 randomised controlled trials of mammographic screening have shown what outcome?
There is a 30% reduction in mortality in women who are screening over the age of 50.
No trials showed a mortality benefit in women under the age of 50.
What is the aim of screening for breast cancer?
To identify pre-invasive disease or invasive disease before dissemination
Which screening technique is the most sensitive and specific?
X-ray mammography
When is X-ray mammography most sensitive?
Once involution of breast tissue has occurred, i.e. post-menopausal women
In which women is X-ray mammography less sensitive?
In women with dense breasts- those with predominately glandular tissue or residual stromal tissue
Which screening test is used in young women with a family history of breast cancer?
MRI with dynamic intravenous contrast
Why is the breast compressed during a mammography?
To flatten the breast tissue to reduce movement, overlapping shadows and radiation dose.
Approximately how many cancers per 1000 screen women are found?
10
What is an interval cancer?
A cancer that occurs in the interval between two screening episodes
How do breast cancers commonly present? (6)
- Abnormal screening mammogram (accounts for 25% of cases)
- Breast lump or thickening
- Axillary tumour
- Breast skin changes; dimpling, puckering, erythema
- Nipple changes; inversion, discharge, rash (Paget’s disease)
- Persistent breast tenderness and or pain
In terms of breast anatomy, what are the ligaments found within the best called?
Cooper’s ligaments
What is the triple assessment used to diagnose breast cancer?
- Full clinical examination
- Bilateral mammography
- FNA cytology or core biopsy (CB is preferred)
TNM staging is used in breast cancer, however it is extensive. How many classifications of T are there?
13 ranging from Tis, T1 to T4d
N staging is just as extensive, with 16 groups. If it states pN, what does the p appear to stand for?
Positive axillary nodes
What is the management of non-invasive (in situ) breast cancer? (this includes DCIS and lobular carcinoma in situ (LCIS)
- Simple mastectomy
- Wide excision alone
- Wide excision and adjuvant radiotherapy
- Adjuvant hormone therapy
In terms of TNM staging, what is defined as early breast cancer?
T 1-3
N 0
M 0
Management of early invasive breast cancer generally involves? (3)
- Surgery - either wide local excision or mastectomy
- Possibly axillary surgery
- Sentinel node biopsy
Which drug is used to treat breast cancers which overexpress HER2?
Trastuzumab
In addition to chemotherapy, targeted therapies and endocrine therapy, what other drug is often prescribed alongside to aid the treatment prevention of hypercalcaemia?
Bisphosphonates
Breast and prostate cancers share a similarity - what is that?
Both hormone related
Which syndrome is p53 related to?
Li Fraumeni’s syndrome - inhertied familial predisposition to range of cancers
Excess fat tissues release which hormone that can contribute to development of cancer?
Oestrogen
What can the ‘orange peel’ appearance of the breast be mistaken for?
Mastitis
What can orange peel appearance of the breast sometimes be?
Inflammatory breast cancer which can spread quickly and should not be ignored
What type of discharge from the nipple is most worrying?
Blood (green or white etc is less worrying but can still indicate a cancer)
What history needs to be taken when screening for breast cancer? (8)
- How long?
- Skin/nipple changes?
- Assess symptoms - discharge/pain?
- Related to menstrual cycle?
- Previous breast lumps?
- Lumps under arm?
- Family history?
- PMH
When someone has presented with possible breast cancer, what examination needs to be performed? (3)
- Breast - including skin and nipple
2. Axilla/SCF
When would you do blood tests in someone with suspected/confirmed breast cancer? (3)
- Pre-operatively
- Concern about metastasises
- Tumour markers - Ca15.3, CEA
Triple assessment involves which three specialties?
- Clinician
- Radiologist
- Pathologist
Behaviour of the cancer is determined by its protein expression - which proteins are these?
- Oestrogen receptor positive/negative
- Progesterone receptor positive/negative
- HER2 - higher the expression of this protein, the worse the prognosis
Cancer is divided into three types?
- Triple negative - but this is bad as they express other proteins
- HER2 positive (herceptin is used to treat this)
- ER or PR positive
What do adjuvant therapies do?
Targets the microscopic disease
While cancer is growing in the breast, what else can it do?
‘Throw off’ little cells which travel elsewhere in the body and can become metastatic - hence why chemo and radiotherapy are used in conjunction with surgery
When is neb-adjuvant treatment used?
Any treatment given with the intent to de-bulk
Why is chemotherapy given in cycles?
To allow the cells in the body to recover - bone marrow to produce new cells
How many cycles is normally the maximum?
8 - as each time the chemotherapy builds up in the body and will lead to greater toxicity
What are the affects of chemotherapy toxicity?
- Fatigue
- Hair loss
- Nausea and vomiting
- Mucositis
- Gastritis
- Diarrhoea/constipation
- MYELOSUPPRESSION - neutropenic sepsis
- Thrombocytopenia
- Organ specific
What does it mean that the breast cancer is oestrogen receptor positive?
It expresses an oestrogen receptor on the surface of the cancer cells, which will accept (bind to the receptor) oestrogen in the body and use it to grow
Why is oestrogen-receptor positive cancer better for prognosis?
Because you can remove the oestrogen from the body and then the cancer cannot use oestrogen to grow
How does tamoxifen work?
Tamoxifen is a competitive inhibitor for oestrogen receptors on the cancer cell surface - and blocks the receptor from oestrogen
What are the adverse effects of tamoxifen? (5)
- Mood changes
- Clot - DVT (check for swollen legs/acute chest pain)
- Vasomotor
- Vaginal discharge
- Loss of libido
What is herceptin?
Monoclonal antibody
What treatment is recommended for any cancer that is bleeding/fungating?
Radiotherapy
What can cancer cells do to T-lymphocytes?
Block the activity of T-cells
What does immunotherapy act to do?
Stop cancer cells from blocking the action of T-cells
What are the adverse effects of aromatase inhibitors? (7)
- Vasomotor
- Mood changes
- Vaginal dryness
- Loss of libido
- Body image
- Arthralgia and myalgia
- Decrease in bone density