Repro 11.2.2 Breast Cancer Flashcards
How common is breast cancer?
Accounts for 20% of all malignancies in women
1 in 12 women develop breast cancer in their life
1% occurs in men
95% are adenocarcinomas (other malignant tumours of the breast are very rare
What increases mens risk of breast cancer?
Klinefelter’s syndrome
Male to female transexuals
Men treated with oestrogen for prostate cancer
Where are breast cancers most common?
Upper outer quadrant (50%)
What are the risk factors for development of breast cancer?
Gender Uninterrupted menses Early menarche (<11) Late menopause Obesity and high fat diet Exogenous oestrogens (HRT, OCP) Liver cirrhosis (All to do with hormones) Atypical changes on previous biopsy (4-5 times) Previous breast cancer (x10) Radiation
What factors reduce risk of breast cancer?
Reproductive history - parity and age at first full term pregnancy and amount of pregnancies
Breast-feeding
How does geography influence the risk of development of breast cancer?
Higher incidence in US and Europe. Possible explanation in diet, physical activity, breast-feeding and environmental factor
What % of breast cancers are hereditary?
10%
What genes are most commonly implicated in breast cancer?
3% of all breast cancers and 25% of hereditary breast cancers are attributed to mutations in BRCA1 or BRCA2
p53
Which BRCA gene is also implicated in ovarian cancer?
BRCA2
What are BRCA genes?
Tumour supressor genes - their proteins repair damaged DNA
What % of the population have BRCA germ line mutations?
0.1%
What is the lifetime breast cancer risk for female carriers of BRCA1?
60-85%
May undergo prophylactic mastectomy
When are familial breast cancers usually diagnosed in comparison to sporadic cases?
20 years earlier on average
What are the classification of breast carcinoma?
In situ or invasive
Ductal or lobular
What are carcinomas in situ?
Neoplastic population of cells limited to ducts and lobules by basement membrane, myoepithelial cells are preserved
Does not invade into vessels and therefore cannot metastasise
How do most DCIS present?
Mammographic calcifications (clusters or linear and branching) but can also present as a mass
How does DCIS appear microscopically?
Often shows central necrosis with calcification
How might DCIS spread?
Can spread through ducts and lobules and be very extensive
What is DCIS?
Ductal carcinoma in situ. Non-obligate precursor of invasive carcinoma
How can Paget’s disease present in the breast?
Unilateral red crusting nipple
What might Paget’s disease of the nipple be mistaken for?
Eczematous or inflammatory conditions of the nipple - should be regarded as suspicious and biopsy performed
What is the pathophysiology of Paget’s disease in the nipples?
Malignant cells can infiltrate epidermis via the mammary duct epithelium. The cells proliferate leading to thickening of the affected skin
Define an invasive carcinoma.
Invaded beyond BM into stroma. Can invade into vessels and can therefore metastasise to lymph nodes and other sites
How does an invasive carcinoma present?
Usually as a mass or mammographic abnormality. By the time a cancer is palpable more than half the patients will have axillary lymph node metastases
What is peau d’orange?
Involvement of lymphatic drainage of the skin gives rise to a dimpled affect by the hair follicles as oedema swells the skin surrounding them. A clinical appearance of breast cancer
What are the most common types of invasive carcinoma of the breast?
Invasive ductal carcinoma, no special type (IDC NST) (70-80%)
Invasive lobular carcinoma (5-15%)
Tubular, mucinous etc
What is the appearance of well/poorly differentiated IDC NST?
Well-differentiated - tubules lined by atypical cells
Poorly-differentiated - sheets of pleomorphic cells
What is the 10 year survival rate for IDC NST?
35-50%
What is the microscopic appearance of invasive lobular carcinoma?
Infiltrating cells in a single file
Cells lack cohesion
What is the prognosis of invasive lobular carcinoma?
35-50% 10 year survival rate
What are the patterns of metastasis of breast cancer?
Lymph nodes via lymphatics (usually ipsilateral axilla)
Distant metastases via blood vessels - bone, lung, liver, brain
Where might invasive lobular carcinoma spread?
Peritoneum Retroperitoneum Leptomeninges Gastrointenstinal tract Ovaries Uterus
What factors determine the prognosis of breast cancer?
In situ v invasive Histological subtype - IDC NST has poorer prognosis Tumour grade Tumour stage Gene expression profile
What is the basis of tumour staging?
Tumour size
Locally advanced disease - invading into skin or skeletal muscle
Lymph node metastases
Distant metastases
How is breast cancer investigated and diagnosed?
Triple approach:
- Clinical - history, fx, examination
- Radiographic imaging - mammogram and ultrasound scan
- Pathology - fine needle aspiration cytology (FNAC) and core biopsy
What is looked for in mammographic screening?
Asymmetric desities
Parenchymal deformities
Calcifications
How are abnormalities seen in mammographic screening further assessed?
Further imaging
FNAC
Core biopsy
What are the local treatment options for breast cancer?
Breast surgery - mastectomy or breast conserving surgery
Axillary surgery - extent depending on whether there are involved lymph nodes (sentinel node sampling or axillary dissection)
Post-operative radiotherapy to chest and axilla
How is the type of breast surgery required determined?
Patient choice
Size
Site of tumour
Size of breast
What is sentinel lymph node biopsy?
Intraoperative lymphatic mapping with dye and/or radioactivity of the draining or ‘sentinel’ lymph node(s) - this is the one most likely to contain breast cancer metastases
If the sentinel node(s) is negative axillary dissection can be avoided
What is the systemic therapeutic approach to treatment of breast cancer?
Chemo (only if benefits thought to outweigh risks)
Hormonal/herceptin treatment (depending on hormone/Her2 receptor status)
What is neoadjuvant chemotherapy?
Given before surgery
What is Her2?
A member of the human epidermal growth factor receptor family
Encodes a transmembrane tryosine kinase receptor
What is herceptin?
humanised monoclonal antibodies against the Her 2 protein
How do oestrogen receptors appear under the microscope?
Brown stained nuclei
How do Her2 receptors appear under the microscope?
Blue stained nuclei, brown cytoplasm
How is the survival for breast cancer improved?
Early detection Neoadjuvant chemo Use of newer therapies Gene expression profile Prevention of familial cases
