Breast Cancer Flashcards
Epidemiology of breast cancer:
Most common form of cancer in females (along with lung and bowel)
1 in 8 women affected
Incidence is increasing
1% of cancers in men
What is a Ductal Carcinoma in situ? (DCIs)
Pre-cancerous and non-invasive lesion of the breast tissue
Usually detected through screening mammography
Abnormal cluster of cells lining the lactiferous ducts
Lobular carcinoma in situ are rarer and tend to be multifocal
Do oestrogen positive cancers have a better prognosis than HER2 amplified cancers?
Large proportion of breast cancers are oestrogen positive and have a better prognosis
More efficient hormone treatment can be given like Tamoxifen
Cancers over-expressing Human Epidermal growth factor 2 are more aggressive with poorer prognosis
Risk factors for Breast cancer
Age (80% of breast cancers occur after menopause)
Extensive family history
BRAC1/2 or HER2 tumour suppressor gene positive
Past medical history of breast cancer
Hormone replacement therapy
Early menarche or late menopause (prolonged increased levels of oestrogen),
DCIS or CIS,
Contraceptive pill,
Nulliparity
What are protective factors for breast cancer?
Regular physical activity
Breastfeeding
Healthy diet
Aspirin and NSAID medications.
Principals of screening:
Cost-effective,
The condition must be an important health problem
There should be a recognisable latent phase
The natural history of the condition should be adequately understood
There should be an accepted and effective treatment for patients
The screening technique must have a high level of accuracy, be acceptable and have facilities
present.
How is screening performed for breast cancer?
Every 3 years for ages 47-72 via mammogram
Positive predictive value is low so several false negatives - more common in younger women due to denser breast tissue
Mammograms also detect DCIs
Organisation of breast cancer services in the NHS:
Mammogram: uses low-energy x rays
Results given in 2 weeks and around 4-7% women recalled to assessment clinic
Ultrasound, wine bore needle biopsy and examination performed here
Screening offered to younger women if there is a high risk.
Will have predictive genetic testing for BRAC1/2 tumour suppressor gene mutation which is hereditary (first degree relative with a diagnosis is tested for gene, then the patient at risk)
Strengths and limitations of mammography in screening:
Strengths:
Cost-effective,
Acceptable procedure,
Relatively quick.
Limitations:
Low sensitivity and specificity,
Several false negatives and false positives
Cannot distinguish between DCIS and breast tumour
Patients report that the procedure can be painful; potential deterrent.
Why do we use ultrasound and biopsy to finally diagnose breast cancer?
Ultrasound is a more specific imaging technique
Higher specificity and sensitivity
Can distinguish between DCIs and cancer
Not uncomfortable or painful and can be used in anxious patients
Biopsy (fine needle aspiration cytology) performed at increased suspicion of cancer. Fulfils the triple assessment (avoids misdiagnosis). Definitive test and can distinguish between benign and malignant.
What is the triple assessment and how do we rate each modality?
Triple assessment combining clinical examination, radiology and biopsy.
Each modality rated from 1-5 with an increased score meaning increased suspicion of cancer
Multimodality investigations are essential as they cover all aspects of breast cancer presentation.
With the three modalities hoping to reduce the chance of over diagnosis and overtreatment when
not necessary.
Types of biopsy that can be done:
Fine needle aspiration - Most reliable and good to differentiate cancer from lumps
Large-bore Core biopsy - histological confirmation and predictive factors e.g. grade, oestrogen positivity. Can bruise, be costly and cause discomfort
Sentinel node biopsy - to see if cancer has spread into lympathic system. Needed to stage cancer and help decide treatment. TNM tumour staging
Mammotome biopsy (vaccum)- large volumes of biopsy in case of diagnostic doubt. Can remove small benign lesions. Time consuming
What are the common clinical features of breast cancer?
- Lump - painless, hard, irregular and are fixed to the skin or muscle. Can enlarge over a short period of time. with distortion of breast shape.
- Nipple discharge - clear, dark or blood. May arise from duct ectasia
- Nipple retraction or ingrowth of skin - When cancer infiltrates suspensory ligaments of Cooper causing ptosis of the breast and inward pull of skin. Both breasts should be compared
- Pain - Rare. Normally with mastitis.
- Systemic symptoms - anorexia, nausea, vomiting, weight loss, fatigue
What is a fibroadenoma?
Benign and second most common benign breast lesion.
Mixture of stromal and epithelial cell growth mass in lobule.
Hormone related and usually regress after menopause.
Smooth, firm, mobile and painless lumps
Women aged 15-35
Core biopsy taken
Excise if more than 3 cms, rapidly increasing in size and patient’s wish
What is duct ectasia and how does it lead to nipple discharge?
Dilatation of the lactiferous ducts. They become blocked and the secretions become
stagnant, which would leak out the nipple as a dark brown fluid. There
will be nipple retraction and a lump.
This is a differential diagnosis as well.
What are the potential differentials for a patients with a lump?
Potential differentials - fibroadenoma, lipoma, papilloma and
hamartoma.
What is a lipoma?
Benign tumour composed of adipose tissue.
Soft to touch, mobile and generally painless.
Most commonly found in adults between the age of 40 and 60, although they may occur in people younger.
What factors cause a delayed presentation of symptoms in primary care?
Patient delay (interval between patient first noticing the symptom and first consulting) causes:
- Older age,
- Socio-economic status and education,
- Non-white ethnic origin,
- Awareness and interpretation of symptoms,
- :Wait and see approach” with denial, self-diagnosis and self-medicating,
- Fear of diagnosis, investigations and treatment,
- Lack of social support
Practitioner delay - Young ages and male patients not referred as quickly. Symptoms other than lump cause delay due to non-specificity
System delay - Misdiagnosis, treating symptomatically, failure to adequately exam, inappropriate tests
What is lymphoedema?
Localised fluid retention and tissue swelling caused by a
compromised lymphatic system.
Seen secondary to axillary lymph node dissection, breast surgery and/or radiation therapy
Why is their a risk of lymphoedema with breast cancer?
Lymph nodes and vessels that are damaged or removed cannot be replaced. This can affect the lymphatic system’s ability to drain fluid in this area, and lymph fluid can build up in the surrounding tissues.
Lymphoedema may develop soon after treatment but it can also occur many years later and may be triggered by a skin infection (cellulitis) or possibly injury.
Sometimes lymphoedema can be due to cancer cells blocking the lymphatic system.
What are the stages of lymphoedema
- Latent - lymph vessels have some damage but not yet apparent. transport capacity is sufficient.
- Spontaneously reversible - tissue is still at pitting stage but is reversed with pressure and elevation. Limb is normal size in the morning
- Spontaneously irreversible - tissue has a spongy consistency when pressed, bounces without indentation and some fibrosis. hardening of limbs and increasing size
- Lymphostatic elephantiasis - swelling is irreversible, limb markedly larger, tissue hard, fibrotic, heavy and unresponsive
Management of lymphoedema:
- Complete decongestive therapy - manual manipulation of lymphatic ducts, short-stretch compression bandaging, exercise and skin care
- Intermittent pneumatic compression - multi chambered pneumatic sleeve with overlapping cells to promote lymph movement. Home treatment and simple
- Surgery: suction assisted lipectomy, vascularised lymph node transfer (lymph from groin is harvested with their supporting artery into axilla), Lymphaticovenous anastomosis (circulation between blood and lymph being reconnected)
What is the role of family history is developing breast cancer?
BRAC mutation is autosomal dominant. Makes women 3-7 times more likely to develop breast cancer.
What is the role of family history is developing breast cancer?
BRAC mutation is autosomal dominant. Makes women 3-7 times more likely to develop breast cancer.
10% of women have familial breast cancer and 3% have detectable mutations in BRAC1, BRAC2 and TP53
What is the referral criteria for family history risk assessment?
-One first degree family relative diagnosed with breast cancer younger than 40,
-One first-degree male relative diagnosed with breast cancer at any age,
-One first-degree relative with bilateral breast cancer where the first primary was diagnosed
at younger than 50 years of age,
- Two first-degree relatives, or one first-degree and one second-degree relative, diagnosed
with breast cancer at any age,
- One 1st/2nd degree relative diagnosed with breast cancer at any age and one 1st/2nd
degree relative diagnosed with ovarian cancer at any age,
- Three first-degree or second-degree relatives diagnosed with breast cancer at any age.
What are reduce risk factors?
Smoking cessation Alcohol intake Increased excercise Contraceptive pill Breastfeeding
Chemoprevention therapies can be offered to women at high risk:-
- Pre-menopausal women can have tamoxifen for 5 years
- Anastrozole should be offered to post-menopausal women for 5 years (unless osteoporosis)
- Risk reducing mastectomy
- Oophrectomy
P scoring system for breast examination
P1 - normal P2- Benign P3 - Indeterminate P4 - Suspicious P5 - Malignant
Accessory nipple
1-5% of population have this
Usually develop along the milk line
Most common site is for accessory nipple is below the breast and accessory breast is in axilla
Rarely require treatment except cosmetic reasons
What is the Oncotype Dx test?
The Oncotype DX test is a genomic test that analyzes the activity of a group of genes that can affect how a cancer is likely to behave and respond to treatment. Used to
- to help doctors figure out a woman’s risk of early-stage, estrogen-receptor-positive breast cancer coming back (recurrence)
- how likely she is to benefit from chemotherapy after breast cancer surgery
- woman’s risk of DCIS coming back
- the risk of a new invasive cancer developing in the same breast,
- how likely she is to benefit from radiation therapy after DCIS surgery
What local treatment can be given?
Local excision, mastectomy and conservation. Radiotherapy is given to the conserved breast and chest wall to reduce local recurrence.
Risk of lymphoedenopathy is increased if radiotherapy is given with full dissection of axilla.
Anti-oestrogen drugs
Pre menopausal women:
Oophrectomy, GnRH analogues (goserelin, leuprorelin)
Tamoxifen (mixed oestrogen receptor agonist and antagonist)
Fulvestrant - more selective SERM
Post menopausal:
Aromatase inhibitors - anastrozole, letrozole, exemestane
Adjuvant therapy of choice in post-menopausal women:
AIs such as anastrozole because they avoid adverse effects of tamoxifen such as venous thromboembolism and achieve a greater reduction is metastasis
What other cancers are associated with BRCA gene?
Breast
Ovary
Prostate
Pancreas
Side effects of tamoxifen?
Hot flushes weight gain mood changes vaginal discharge thromboembolism
But bone protective
Side effects of aromatase inhibitors
Hot flushes Osteoporosis - bone thinning (everyone needs to have a DEXA scan 3 months of starting therapy) Arthralgia Skin rash Adverse lipid profile Vaginal dryness
Herceptin:
Monoclonal Antibody
Interferes with HER2 Receptors (over-expressed in 20% of Breast Cancers ,associated with aggressive growth and poor clinical outcome)
Injection/3 weeks for a year
Improves disease free and overall survival
Cardiomyopathy
What adjuvant chemotherapy can be used?
- Adriamycin and Cyclophosphamide, (AC), cycles 3 weeks apart.
- Taxanes e.g docetaxal
- 6 cycles of Chemotherapy
- CMF was standard up to few years ago, (Cyclophosphamide, methotrexate, fluorouracil)
Where do the 3 types of endocrine therapies act?
How long do we give these for?
Tamoxifen acts on the active oestrogen receptor in breast cancer cell.
Gosrelin acts on the pituitary gland to reduce LH/ FSH secretion. AIs act on androgen receptors in adrenal glands.
Given for 5 years
1) What is the lympathic drainage of the breast
2) Axillary nodes lie at which level
3) key structures to preserve in axillary space
1) Axillary nodes (97%) and internal mammary nodes (3%)
2) Level 1-3
3) Long thoracic nerve of bell
Thoracodorsal pedicle
When do we perform breast conservation?
Small tumour relative to breast size
No previous radiotherapy to breast
Pre-operative chemo may allow breast conservation
Patient choice
When do we perform a mastectomy?
Large tumour relative to breast size
Multifocal cancer
May have immediate or delayed reconstruction
Patient choice
Describe the TNM tumour staging:
T0 No evidence primary T1 <2 cm T2 2-5 cm T3 >5 cm T4 Extends to chest wall or skin or inflammatory
N0 No Nodes
N1 Mobile Nodes
N2 Fixed/matted nodes
N3 Internal Mammary nodes
M0, no Metastases/M1, Metastases
What is the Nottingham prognostic index?
Refers to Prognosis if no treatment other than surgery. May improve significantly with adjuvant chemo and hormone therapy.
Grade (1-3) + Nodes (1-3) + 0.2x size (cm)
What is a galactocoele?
Milk filled cyst from over distension of a lactiferous duct.
Presents as a firm non tender mass in the breast,
Commonly in upper quadrants beyond areola.
Diagnostic aspiration is often curative
Phylloids tumour
Rapidly growing
One in four malignant
One in Ten Metastasize
Create bulky tumors that distort the breast
May ulcerate through the skin due to pressure necrosis
Treatment consists of wide excision
Cystic breast mass:
Common cause of dominant breast mass
May occur at any age, but uncommon in post menopausal women
Fluctuates with menstrual cycle
Well demarcated from the surrounding tissue
Characteristically firm and mobile
May be tender
Difficult to differentiate from solid mass
Treatment Aspiration
What surgical treatments are available for the breast?
Radical Mastectomy - removal of breast, LN and pectoral muscle
Modified radical mastectomy - pectoral muscle preserved
Wide local excision - 1/2 cm margin of normal breast tissue and no skin
Lumpectomy
Quadrantectomy
What is meant by Multifocal and multi-centric disease?
Multifocal - multiple tumours in same breast quadrant
Multicentric - multiple tumours in different quadrants
What does the Halstedian paradigm say?
The only way the cancer can progress is through lymoh nodes hence why they started removing them.
But this didn’t improve survival
This was replaced by Fisherian paradigm
How would fat necrosis present?
Mimics cancer
Ill-defines mass, inverted nipple
Skin tethering
Cytology would show benign cells
What are poor prognostic factors for breast cancer?
Young age Pre-menopausal status Large tumour size High tumour grafe HER2 receptor negative Positive nodes
What is a intraductal pappiloma?
A wart-like lump that develops in one or more milk ducts in breast
What is a haematoma?
Blood filled mass caused by injury or surgical procedure to the breast
Who has overall responsibility for specialist advice, palliative treatments and liaison with other specialities?
Palliative medicine physician
What kind of pain does fibrocystic disease of the breast produce?
Cyclical breast pain
