What does the incidence of breast tumour malignancy rise with?
Are breast lesions in young females usually benign or malignant?
Describe the histology of breast tissue?
Modified sweat gland
Background of adipose and connective tissue
Many ducts (15-25) that lead to nipple - branch repeatedly in stroma > terminal part of duct leads into lobule
Lobule composed of numerous acini
Describe the histology of the acini?
Inner secretory layer
Outer myoepithelial layer
Where do most breast lesions arise from?
Epithelium of terminal duct lobular unit
Describe the possible clinical presentations of a breast lesion?
Change in shape
Describe fibrocystic change of the breast?
Very common, usually in later reproductive years
Apocrine metaplasia (epithelial cells become pink and granular)
May be asymptomatic or produce lumps and discomfort
Describe the investigations that should be carried out when a possible breast lesion is present?
Clinical history and examination
Radiology: US and/or mammography
Describe the rationale behind mammography?
Looks at radio density of breast
Pathology will show up differently to normal breast
Look for patterns of calcification
Why are biopsies of breast lesions performed?
To ensure that a lesion is malignant before commencing treatment
How are biopsies of breast lesions performed?
Which method is preferred and why?
Fine needle aspiration or needle core/tru-cut biopsy
Core/tru-cut preferred as it takes out an actual piece of tissue, so we can see the relationship of cells to each other, the stroma and basement membrane
Solitary, well circumscribed, benign mass
Most common in younger women
Neoplastic or hyperplastic stromal tumour (fibroblasts in stroma predominate)
Minimal increased risk of malignancy
Approximately how many women will be diagnosed with breast cancer?
What is the average age of diagnosis?
1 in 8 diagnosed before the age of 85
Avergae age of first diagnosis is 60 years
Describe the predisposing factors to breast cancer?
Age: more time to accumulate mutations
Genetic factors: most are due to sporadic mutations, but there are some familial cases
Increased oestrogen exposure: stimulates proliferation
Environmental and dietary influences: obesity, alcohol
Past history of certain breast diseases
Describe the sporadic mutations that may give rise to breast cancer?
Somatic mutations in p53 (cell cycle arrest, reapir of DNA damage)
Mutations in HER2 (proto-oncogene, epidermal growth factor receptor on cell surface)
Describe the germline mutations that may give rise to breast cancer?
(TSGs, involved in cell cycle arrest and DNA repair)
Inherited in autosomal dominant fashion
Onset at younger age
May also develop other tumours
Describe why postmenopausal obesity may predispose to breast cancer?
Adipose tissue can make oestrogen > oestrogen stimulates proliferation of cells
Describe the effect of breast feeding on breast cancer risk?
Lactation > ovulation suppressed > decreased oestrogen
Describe hyperplasia of the breast tissue?
Non-neoplastic proliferation of breast epithelium
With or without atypia
Usually an incidental finding when testing for something else
Does not cause symptoms
Predicts risk of future cancer development
What is in situ carcinoma of the breast?
Describe the risks associated with it?
Malignant population of cells confined to ducts and/or acini, no invasion through basement membrane
Associated with increased risk of developing invasive tumour
Describe the two types of breast carcinoma in situ?
Ductal carcinoma in situ: most common, frequently associated with calcification seen on mammogram
Lobular carcinoma in situ: incidental finding on biopsy
What is Paget's disease of the nipple?
Malignant cell sof DCIS may extend up ducts to the nipple
Inflammation, erythema and exudate of nipple
What are the two main types of invasive carcinoma of the breast?
Invasive ductal carcinoma: most common
Invasive lobular carcinoma
Describe the characteristics of invasive ductal carcinoma?
50% in upper outer quadrant
Typically firm stellate mass
Tumour cells form glandular lumen
Describe the charcateristics of invasive lobular carcinoma?
Long, thin, individual single files of tumour
Where does invasive breast carcinoma spread to?
Local: skin, nipple, underlying muscle/chest wall, pleura
Metastatic: lymphatic (axillary), blood > lungs, bone, liver, brain, etc.
Describe the management options for breast cancer?
How is appropriate treatment determined?
Determined by characteristics of primary tumour and stage
Describe the role of pathology in the diagnosis and treatment of breast cancer?
Pre-treatment: characterisation of tumour (diagnosis, staging, treatment)
Post-surgical: completeness of surgery, prognostic features (including staging), adjuvant therapy?
Describe the surgery options for treatment of breast cancer?
Quadrantectomy: breast-conserving, also samples lymph nodes
Describe the difference between axillary clearance and lymph node sampling?
Why are these prcedures necessary?
Axillary clearance: remove all lymph nodes
Sampling: remove/sample a few nodes
Performed to determine whether or not cancer is present in node
Describe why breast cancer are histologically typed?
Gives a good indication of prognosis
Describe the grading of breast cancers?
Scores for: acinar/tubule formation, nuclear pleiomorphism, mitotic index
Grade 1 - low grade
Grade 2 - intermediate grade
Grade 3 - high grade
Describe the survival rates for the different grades of breast cancer?
Poorer survival for higher grades
Describe the factors which may lead to a poorer prognosis for breast cancer?
Tumour size (larger)
Lymphovascular space invasion (higher likelihood of nodal metastases)
Surgical margins (incomplete excision)
Hormone receptors: ER and PR
When are transtuzumab/herceptin used in the treatment of breast cancer?
When HER2 amplification is present
How does the presence of HER2 amplification alter the treatment of breast cancer?
Requires use of transtuzumab/herceptin
Describe the staging of breast cancer?
TNM4: invasive carcinoma of any size, distant metastases
Describe the common chnages that occur to male breast tissue?
Gynaecomastia: increase in size of male breast tissue, due to proliferation of ducts and stroma
Breast carcinoma: 1% that of women