Breast Disease Flashcards
Describe normal breast tissue in general.
Modified sweat glands
Non-functional except during lactation
Lobules = acini and intralobular stroma
Describe the physiological breast changes that a women goes through.
Prepubertal breast - few lobules (before puberty male and female breasts are identical)
Menarche - increase in number of lobules, increased volume of interlobular stroma
Menstrual cycle - follicular phase lobules quiescent, after ovulation cell proliferation and stromal oedema, with menstruation see decrease in size of lobules
Pregnancy - increase in size and number of lobules, decrease in stroma, secretory changes
Cessation of lactation - atrophy of lobules but not to former levels
Increasing age - terminal duct lobular units (TDLUs) decrease in number and size, interlobular stroma replaced by adipose tissue (mammograms easier to interpret)
What are the general clinical presentation of breast conditions?
Pain Palpable mass Nipple discharge Skin changes Lumpiness
Mammographic abnormalities
What sort of pain presentation will someone with a breast disease present with?
May be cyclical and diffuse, in which case often physiological
Non-cyclical and focal - ruptured cysts, injury, inflammation
Occasionally presenting complaint in breast cancer
Tell me about palpable masses found in breasts.
May represent normal nodularity Most worrying if hard, craggy and fixed Causes include: - Invasive carcinomas - Fibroadenomas - Cysts No woman should be allowed to have a lump in the breast without a firm diagnosis
Tell me about nipple discharge.
Most concerning if spontaneous and unilateral
Milky - endocrine disorders e.g. pituitary adenoma; side effect of medication e.g. OCP
Bloody or serous - benign lesions e.g. papilloma, duct ectasia; occasionally malignant lesions
Tell me about mammographic abnormalities.
Found during mammographic screening
Easier to detect lesions in breasts of older women
Women between 47-73 years invited every 3 years
Worrying findings include densities and calcifications
- Densities - invasive carcinomas, fibroadenomas, cysts
- Calcifications - ductal carcinoma in situ (DCIS), benign
changes
Tell me about the incidence of breast conditions in general.
Breast symptoms and signs are common
Most breast symptoms and signs will be benign
Fibroadenoma most common benign tumour
Breast cancer most common non-skin malignancy in women
Mammographic screening increases detection of small invasive tumours and in situ carcinomas
Give the incidence of fibroadenomas.
Can occur at any age during reproductive period
Often
Give the incidence of breast cancer.
Rare before 25 years (except for some familial cases) Incidence rises with age 77% occurs in women >50 years Average age at diagnosis is 64 years In UK: - 45,500 new female cases and 300 new male cases a year - 12,500 deaths per year
What are general types of pathological conditions of the breast?
Disorders of development Inflammatory conditions Benign epithelial lesions Stromal tumours Gynaecomastia Breast carcinoma
Give an example of a disorder of development.
Milk line remnants - polythelia (third nipple), accessory axillary breast tissue (and potential breast tissue malignancies associated)
Name some inflammatory conditions of the breast.
Acute mastitis
Fat necrosis
Describe acute mastitis.
Almost always occurs during lactation
Usually Staphylococcus aureus infection from nipple cracks and fissures
Erythematous painful breast, often pyrexia
May produce breast abscesses
Usually treated by expressing milk and antibiotics
Describe fat necrosis.
Present as a mass, skin changes or mammographic abnormality (can be misinterpreted as cancer)
Often history of trauma or surgery
Can mimic carcinoma clinically and mammographically
Describe benign epithelial lesions of the breast.
Fibrocystic change
- Commonest breast lesion
- May present as a mass or mammographic abnormality
- Mass often disappears after fine needle aspiration (FNA)
- Histology - cyst formation, fibrosis and apocrine
metaplasia
- Can mimic carcinoma clinically and mammographically
Give examples of stromal tumours of the breast.
Fibroadenoma, phyllodes tumours, lipoma, leiomyoma, hamartoma
Describe fibroadenomas of the breast.
Present with a mass, usually mobile, or mammographic abnormality
‘Breast mouse’ - mobile and elusive
Can be multiple and bilateral
Can grow very large and replace most of the breast
Macroscopically - well circumscribed, rubbery, greyish/white (squash ball)
Histology - composed of a mixture of stromal and epithelial elements
Can mimic carcinoma clinically and mammographically
Localised hyperplasia rather than true neoplasm
Describe phyllodes tumour of the breast.
Rare before 40 years old
Present as masses or as mammographic abnormalities
Benign, borderline and malignant types; most benign, less then 5% malignant
Can be very large and involve entire breast
Histology:
- Nodules of proliferating stroma covered by epithelium
(phullon = leaf)
- Stroma more cellular and atypical than that in
fibroadenomas
Need to be excised with wide margin or may recur
Malignant type behave aggressively, recur locally and metastasize by blood stream
Describe gynaecomastia.
Enlargement of male breast
Unilateral or bilateral
Often seen at puberty and in the elderly
Caused by relative decrease in androgen effect or increase in oestrogen effect
Can mimic male breast cancer especially if unilateral
No increased risk of cancer
Tell me a little bit about breast cancer.
Accounts for 20% of all malignancies in women
Male breast cancer
- 1% of all cases of breast cancer
Approximately 95% are adenocarcinomas
Other malignant tumours of breast are very rare, e.g. primary sarcomas such as angiosarcoma
Most common in the upper right quadrant (approx. 50% occur here)
What are the risk factors of breast cancer?
Major risk factors are related to hormone exposure
Gender
Uninterrupted menses
Early menarche (
Tell me about hereditary breast cancer.
10% of breast cancers
3% of all breast cancers and 25% of familial cancers attributed to mutations in BRCA1 (BReast CAncer associated gene 1) or BRCA 2
- Both tumour suppressor genes - their proteins repair
damage DNA
- 0.1% of population has BRCA1 germline mutations
- Lifetime breast cancer risk for female carriers is 60-85%
- Median age at diagnosis is approximately 20 years
earlier tan sporadic cases
- Carriers may undergo prophylactic mastectomies
Another gene involved in hereditary breast cancer is p53 n(Li-Fraumeni syndrome)
How are breast carcinomas classified?
Divided into in situ and invasive
They can be ductal or lobular
Describe an in situ carcinoma of the breast.
Neoplastic population of cells limited to ducts and lobules by basement membrane (BM), myoepithelial cells are preserved
Does not invade into vessels and therefore cannot metastasize
Describe a ductal carcinoma in situ of the breast.
DCIS
Most often presents as mammographic calcifications (clusters or linear and branching) but can present as a mass
Can spread through ducts and lobules and be very extensive
Histologically often shows central (comedo) necrosis with calcification
Non-obligate precursor of invasive carcinoma
What is Paget’s disease?
Cells can extend to nipple skin without crossing BM = Paget’s disease
- Unilateral red and crusting nipple
- Eczematous or inflammatory conditions of the nipple
should be regarded as suspicious and biopsy
performed to exclude Paget’s disease
Describe an invasive carcinoma of the breast.
Invaded beyond BM into stroma
Can invade into vessels and can therefore metastasize to lymph nodes and other sites
Usually presents as a mass or as mammographic abnormality
By the time a cancer is palpable more than half of the patients will have axillary lymph node metastases
Peau d’orange (orange peal) - involvement of lymphatic drainage of the skin
What are the different types of invasive carcinoma?
Invasive ductal carcinoma, no special type (IDC NST)
- 70-80%
- Well-differentiated type - tubule lined by atypical cells
- Poorly differentiated type - sheets of pleomorphic cells
- 35-50% 10 year survival
Invasive lobular carcinoma
- 5-15%
- Infiltrating cells in a single file, cells lack cohesion
- Similar prognosis to IDC NST
Other types, e.g. tubular (1-2%, excellent prognosis), mucinous (1-6%, excellent prognosis, often older women)
What are the patterns of metastasis of breast cancer?
Lymph nodes via lymphatics - usually in the ipsilateral axilla
Distant metastases via blood vessels - bones (most frequent site), lungs, liver, brain
Invasive lobular carcinoma can spread to odd sites - peritoneum, retroperitoneum, leptomeninges, gastrointestinal tract, ovaries, uterus
What are the factors of determining prognosis in breast cancer?
In situ disease or invasive carcinoma Histological subtype - IDC NST has poorer prognosis Tumour grade Tumour stage: - Tumour size - Locally advanced disease - invading into skin or skeletal muscle - Lymph node metastases - Distant metastases Gene expression profile
Tell me about the relation of gene expression patterns and breast cancer.
Microarrays have been used to identify about 17 marker genes that can correctly identify about 90% of women who would eventually develop metastases
Tell me about the investigation and diagnosis of breast cancer.
Triple approach
- Clinical - history family history, examination
- Radiographic imaging - mammogram and ultrasound
- Pathology -fine needle aspiration cytology (FNAC) and
core biopsy
What are some therapeutic approaches in breast cancer?
Local and regional control
- Breast surgery - mastectomy or breast conserving
surgery
- Decision depends on patient choice, size and site of
tumour, size of breast
- Axillary surgery - extent depending on whether there
are involved nodes (sentinel node sampling or axillary
dissection)
- Post-operative radiotherapy to chest and axilla
Systemic control
- Chemotherapy - if benefits thought to outweigh the
risks, if given before surgery = neoadjuvant
- Hormonal treatment - Tamoxifen, depending on
oestrogen receptor status (80% are ER positive)
- Herceptin treatment - depending on Her2 receptor
status
How do we improve survival from breast cancer?
Early detection - awareness of disease, importance of family history, self-examination, mammographic screening
Neoadjuvant chemotherapy - early treatment of metastatic disease
Use of newer therapies - e.g. Herceptin
Gene expression profiles
Prevention in familial cases
- Genetic screening, prophylactic mastectomies
