Breast cancer + cytology/histology Flashcards
Incidence of Breast Cancer
- High - affects 1 in 8 women
- 55,000 new cases per year in the UK
- Around 300 new cases per year in men
- Screening from age 50-70
Risk factors
- Age - breast cancer is multi-factorial
- Previous breast cancer
- Genetic: BRCA1 and BRCA2 (only 5%)
- Early menarche (periods) and late menopause - due to exposure to oestrogen
- Late or no pregnancy
- HRT - over 10 years on it
- Alcohol >14 units per week
- Weight
- Post Radiotherapy treatment for Hodgkin’s disease
Presentation of Breast cancer
- Asymptomatic - incidental on breast screening (50-70 years)
- Symptomatic - outpatient clinic
Symptoms of breast cancer
- Lump
- Mastalgia (persistent unilateral breast pain)
- Nipple discharge (blood-stained)
- Nipple changes (Paget’s disease, retraction)
- Change in the size or shape of the breast
- Lymphoedema (Swelling of the arm - if cancer is already advanced - lymph cannot drain properly)
- Dimpling of the breast skin

What 3 things are done when a patient comes to a clinic with suspected breast cancer?
Called the ‘triple assessment’:
- History and clinical examination
- Radiology - Bilateral mammogram / USS
- Cyto-pathological - FNA (cells only - cytology) or core biopsy (tissue - pathology)
What do you want to find out from the history from your patient?
- Presenting complaint
- symptoms etc
- Previous breast problems
- Cysts
- Fibroadenoma
- Previous cancer
- Family history
- Ovarian or breast cancer
- Have they already had genetic testing? Are they BRCA1 or BRCA2 positive?
- Hormonal status
- Previous pregnancies?
- Menopause
- HRT/Contraception
- Drug history/allergies
- Blood thinning - need to consider if taking biopsy etc
What does a clinical examination in a breast clinic involve?
Chaperone is required - intimate procedure
- Examine both breasts - start with normal breast
- Axillae, supraclavicular region and internal mammary
How can the breast be imaged? (3)
- Mammography
- USS
- MRI - only for lobular type of breast cancer or dense breasts or ladies with other benign diseases (in order to distinguish between them and the cancer)
Which imaging modality is the most sensitive in older women?
Mammography
Why is the sensitivity of mammography reduced in younger women?
Due to increased glandular tissue. For this reason, it is not routinely done in women younger than 35
What can doing a core biopsy tell you?
- About cells and tissue structures
- Malignant cells breach the basement membrane and these are classed as invasive breast cancer
- If within the basement membrane then classed as in-situe disease
- Oestrogen, progesterone and HER2 receptor status
What technique is used to obtain cells for cytology in breast cancer?
Fine needle aspiration
Can also use: direct smear from nipple discharge or scrape of nipple with scalpel (not pleasant)
FNA vs Core biopsy
- When are each of them used?
- What are they useful for?
FNA:
- Gives an immediate confirmation if the lesion is benign.
- Useful in assessing enlarged lymph nodes (solid or fluid filled) or satellite lesions/diffuse area of thickening
- It is done as part of the triple assessment when women attend the breast clinic.
- If inpalpable area then do US-guided FNA
Core biopsy:
- Done in all symptomatic cases where there is either clinical/radiological/cytological suspicion
- Doesn’t give immediate diagnosis
- It is essential for pre-operative classification
- If the clinical and radiological findings are suspicious of malignancy then tend to go straight to core biopsy
- If abnormality detected from breast screening in asymptomatic women then core biopsy is used as it is better at showing micro-calcification or architectural distortion.
Breast cancer is categorised into invasive and non-invasive types.
What are the different types of breast cancer within these categories?
Invasive
- Ductal carcinoma (80%)
- Lobular carcinoma (10%)
- Others (10%)
Non-invasive - commonly picked up from screening as does not form a palpable tumour. Risk of invasion depending on grade (low or high grade)
- Ductal carcinoma in-situ
- Lobular carcinoma in-situ

How is breast cancer staged? i.e what investigations are done to work out the stage of cancer
- Blood tests! - FBC, U+E
- LFT
- Checking for Bone metastases - Ca2+ and PO2-
- Chest x-ray - lung metastases?
- CT chest/abdo/pelvis
- No reliable tumour markers for breast cancer
TNM staging in breast cancer
REMEMBER 2 NUMBERS: 2 and 5
- T1 = tumour size is <2cm
- T2 = 2-5cm
- T3 = >5cm
- T4
- a = tumour invading skin
- b = tumour invading chest wall
- c = tumour invading both
- d = inflammatory breast cancer - most severe
- N0 = no regional lymph nodes palpable
- N1 = regional lymph node palpable - mobile
- N2 = regional lymph node palpable - fixed
- M X – distant metastasis cannot be assessed
- M0 – no distant metastasis
- M1 – distant metastasis
Management/treatment of breast cancer
- Surgery
- +/- radiotherapy
- +/- chemotherapy
- +/- hormonal therapy
What are the 2 main types of surgical procedures done for breast cancer?
- Breast conservation surgery (need radiotherapy too to have the same survival as mastectomy)
- Mastectomy
Who is suitable for breast conservation surgery?
Depends on:
- Breast size/tumour size ratio
- Breast ptosis/sagging or hanging of breasts (occurs when supporting structures of the breast fail)
- If patient is fit enough to have radiotherapy afterwards
- Patient’s choice
Why is axillary dissection/surgery done?
- To examine or remove lymph nodes
- Prognostic information / staging
- Regional control of disease / eradication in the axilla
What is the importance of the Sentinel lymph node?
- First node to receive lymphatic drainage so the first node the tumour spreads to
- If no cancer detected there then reassured that there is no further disease in the armpit – helps stage cancer
When is a Sentinel lymph node biopsy performed?
- Done after cancer diagnosis to help with staging of cancer
- Only performed when pre-operative axillary USS is normal
- If negative = clear of tumour – no spread to lymph nodes
What happens if cancer is detected in the SLN?
Remove all axillary lymph nodes surgically or give radiotherapy to all the axillary nodes
What are the complications of axillary surgery?
- Lymphoedema (10-17%) – mild or severe
- Sensory disturbance (intercostobrachial n.)
- Decrease ROM of the shoulder joint
- Nerve damage (long thoracic, thoracodorsal, brachial plexus)
- Vascular damage
- Radiation-induced sarcoma
What factors increase the chance of breast cancer coming back?
- Lymph node involvement
- Tumour grade
- Tumour size
- Steroid receptor status (er/pr negative)
- HER2 positive
- LVI – lymphovascular invasion
What is the Nottingham prognostic index (NPI)?
A tool used to determine prognosis following surgery for breast cancer.
- Its value is calculated using 3 pathological criteria:
- the size of the tumour
- the number of involved lymph nodes
- the grade of the tumour.
What local and systemic therapies are used for prevention of breast cancer relapse?
Local - radiotherapy
Systemic - hormone therapy, chemotherapy, targeted therapies
Radiotherapy
- Given to all patients after wide local excision (breast conserving) as adjuvant treatment – over 3 weeks
- Boosts given to younger patients – reduce local recurrence
- Only given to women after having mastectomy if there is local or significant lymph node involvement
- Complications
- Immediate – skin reaction
- Radiation pneumonitis
- Osteonecrosis
- Angiosarcoma
Hormone therapy
- Can only be given to women with oestrogen receptor positive cancers
- Blocks stimulation of cell growth by oestrogen
- 2 main groups: Tamoxifen or aromatase inhibitors (arimidex, letrozole)
- Tamoxifen – blocks the receptor by sitting on it - effective in all age groups
- Aromatase – can’t be given pre-menopausal women, inhibits oestrogen synthesis
Chemotherapy
Greatest benefit in higher risk cancers or younger women
Taxane based combinations – latest drugs
Oncotype DX - tool used to determine whether chemo is likely to benefit
Who is HER2 positivity and anti-HER2 therapy given to?
- Given to patients with over-expression of HER2 and given with chemotherapy
Where does breast cancer spread to?
Local
- Skin
- Pectoral muscles
- Contralateral breast
Lymphatic
- Axillary nodes
- Internal mammary nodes
Haematogenous/blood
- Bone
- Lung
- Liver
- Brain
- Bone marrow
Which cells does breast carcinoma arise from?
Epithelial cells of glandular tissue
Benign cytology
- Low/ moderate cellularity
- Cohesive groups of cells (joined together to form the regular layer of epithelial layers and linings)
- Flat sheets of cells
- Bare oval (bipolar) nuclei in background
- Cells of uniform size
- Uniform chromatin pattern - DNA in nucleus is even

Malignant cytology
- Highly cellular - proliferation
- Crowding/overlapping of cells
- Loss of cohesion - dissociated cells
- Nuclear pleomorphism - enlarged and variation
- Hyperchromasia - increased nuclear DNA - stains darker
- Absence of bipolar nuclei - tumour cells wipe out myoepithelial cells

What is the role of cytology in clinic?
To determine whether benign or malignant
Rarely specific
What is the cytology scoring system?
C1-5
- C1 Unsatisfactory/ Insufficient cells for diagnosis
- C2 Benign
- C3 Atypia (probably benign)
- C4 Suspicious (probably malignant)
- C5 Malignant
Look
If a breast lump turns out to be a cyst then aspiration is curative. The fluid is discarded unless:
- It is bloodstained - then examined under microscope
- There is residual mass - examine fluid and aspirate residual lump
Cytology is used for nipple lesions too. What are some common diagnoses?
- Duct ectasia - macrophages only
- Intraduct papilloma - benign cells in papillary groups
- Intraduct carcinoma - malignant cells
- Eczema - squamous cells from epidermis only
- Paget’s disease - squamous cells and malignant cells
Screening for breast cancer
- Mammogram every 3 years
- Women 50-70 years old