Breast Disease Flashcards
What do the breasts start off as embryologically?
Sweat glands
How are the breasts unusual amongst glands?
They are non-functional except during lactation
What are the histological features of the breast?
Lobules with acini and intralobular stroma
Double layer of cells - myoepithelial and epithelila
When do physiological breast changes occur?
Menarche Menstrual cycle Pregnancy Cessation of lactation Increasing age
Describe the histological features of the breast before puberty?
Few lobules - mainly just terminal ducts
Before puberty, male and female breasts are identical
What happens to the histology of the breast at puberty?
Increase in number of lobules, increased volume of interlobular stroma
How do the breasts change with the menstrual cycle?
Follicular phase lobules quiescent
After ovulation cell proliferation and stromal oedema
With menstruation see decrease in the size of lobules
What is the result of the decrease in size of lobules before mensturation?
Some women get pain or discomfort shortly before mensturation
What happens to the breasts in pregnancy?
Increase in size and number of lobules, decrease in stroma, secretory changes
What happens to the breast histology when there is cessation of lactation?
There is atrophy of lobules, but not to former levels
What happens to breast histology with increasing age?
Terminal duct lobular units (TLDUs) decrease in number and size
Interlobular stroma replaced by adipose tissue
What is the result of the interlobular tissue being replaced by adipose tissue in the ageing breast?
Mammograms are easier to interpret- when younger, very dense, so not much use
What are the clinical presentations of breast conditions?
Pain Palpable mass Nipple discharge Skin changes Lumpiness Mammographic abnormalities
When may mammographic abnormalities be the presenting complaint in breast conditions?
Screening
What kind of pain indicates physiological changes?
Cyclical - with menstrual cycle
Diffuse - through most of both breastt
What kind of breast pain can indicate pathological change?
Non-cyclical
Focal
What can cause breast pain?
Ruptured cyst
Injury
Inflammation
Occasionally presenting complaint in breast cancer
What does a palpable mass in the breast indicate?
May represent normal nodularity
May be pathology
When are palpable breast masses most concerning?
When hard, craggy, fixed
What can cause a palpable breast mass?
Invasive carcinomas
Fibroadenomas
Cysts
What is true of all women when they have a palpable breast mass?
No woman should be allowed to have a lump in the breast without a firm diagnosis
When is nipple discharge most concerning?
If spontaneous (rather than occuring when nipple squeezed) and unilateral
What could cause a milky nipple discharge?
Endocrine disorders
Side effect of medication
Give an example of an endocrine disorder that might produce nipple discharge?
Pituitary adenoma
What medication could have nipple discharge as a side effect?
Oral contraceptive
What could cause a bloody or serous nipple discharge?
Benign lesions
Occasionally malignant lesions
What benign lesions could cause nipple discharge?
Papilloma
Duct ectasia
What is duct ectasia?
Enlargement or inflammation of duct
When are mammographic abnormalities found?
During mammographic screening
Who are mammographic abnormalities easier to detect in?
Older women
When are women screened with a mammograph?
When they are 47-73, every 3 years
Why are women 47-73 invited for mammographic screening?
More useful in older women
Malignancies more common
What are the worrying findings on mammographic screening?
Densities
Calcifications
What could cause a density on mammographic screening?
Invasive carcinomas
Fibroadenomas
Cysts
What could cause calcifications on mammographic screening?
Ductal carcinoma in situ (DCIS)
Benign changes
Are breast symptoms and signs common?
Yes
What is true of most breast symptoms and signs?
They will be benign
What is the most common benign breast tumour?
Fibroadenoma
How does breast cancer compare to other forms of cancer in terms of incidence?
It is the most common non-skin malignancy in women
What is the advantage of mammographic screening?
It increases detection of small invasive tumours and in situ carcinomas
At what age can fibroadenomas occur?
At any age during the reproductive period, often <30 years
At what age do most Phyllodes tumours present?
In the 6th decade
At what age is breast cancer rare?
Before 25 years (except for in some familial cases)
What happens to the incidence of breast cancer with age?
It rises
What % of breast cancers occur in women >50 years?
77%
What is the average age of breast cancer diagnosis?
64
Give 6 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 breast development?
Milk line remnants
What conditions can arise from milk line remnants?
Polythelia - third nipple
Accessory axillary breast tissue
Where on the body can polythelia occur?
Anywhere along the milk line - from axilla to vulva
Give two inflammatory conditions of the breast
Acute mastitis
Fat necrosis
What is acute mastitis?
Acute inflammation of the breast
When does acute mastitis occur?
Almost always during lactation or pregnancy
What causes acute mastitis?
Usually S. Aureus infection from nipple cracks and fissues
What are nipple cracks and fissures usually secondary to?
Breastfeeding
What are the symptoms of acute mastitis?
Erythematous painful breast
Pyrexia
What complications can arise from acute mastitis?
Breast abscesses
How is acute mastitis treated?
Expressing milk
Antibiotics
How does fat necrosis present?
Mass
Skin changes
Mammographic abnormality
How does the mass feel in fat necrosis of the breast?
Craggy, fixed feeling - similar to malignancy
What is there often a history of in fat necrosis of the breast?
Trauma
Surgery
What can fat necrosis mimic clinically and mammographically?
Carcinoma
Give a benign epithelial lesion of the breast
Fibrocystic change
How common is fibrocystic change
In autopsy, virtually all women have fibrocystic change
How may fibrocystic change present?
Mass or mammographic abnormality
What often happens to the mass on investigations?
Mass often disappears after fine needle aspiration
How does fibrocystic change appear histologically?
Cyst formation
Fibrosis
Apocrine metaplasia
What can fibrocystic change mimic clinically and mammographically?
Carcinoma
Give 5 examples of stromal tumours of the breast
Fibroadenoma Phyllodes tumours Lipoma Leiomyoma Hamartoma
How do fibroadenomas present?
Mass - usually mobile
Mammographic abnormality
What is the mass termed in fibroadenomas?
Breast mouse
Why is the mass termed a ‘breast mouse’ in fibroadenomas?
Mobile and elusive
How many fibroadenomas is a person likely to have?
May be multiple and bilateral
How do fibroadenomas appear macroscopically?
Well circumscribed
Rubbery
Greyish/white
How do fibroadenomas present histologically?
Composed of a mixture of stromal and epithelial elements
What can fibroadenomas mimic clinically and mammographically?
Carcinoma
Are fibroadenomas true neoplasms?
No, they are localised hyperplasia
How do Phyllodes tumours present?
Masses
Mammographic abnormalities
What are the different types of Phyllodes tumours?
Benign
Borderline
Malignant
What is meant by a borderline Phyllodes tumour?
Grows quicker than benign, and can metastasise
How big are Phyllodes tumours?
Can be very large and involve entire breast
What are the histological features of Phyllodes tumours?
Nodules of proliferating stroma covered by epithelium
Stroma more cellular and atypical than in fibroadenomas
How are Phyllodes tumours?
Need to be excised with wide margin
Why do Phyllodes tumours need to be excised with wide margin?
Otherwise they reoccur, and come back further along the line towards malignancy
What is gynaecomastia?
Enlargement of the male breast
Is gynaecomastia unilateral or bilateral?
Can be either
Is gynaecomastia more concerning when it is unilateral or bilateral?
Unilateral (because breast cancers are unilateral)
When is gynaecomastia often seen?
Puberty
Elderly
What causes gynaecomastia?
Relative decrease in the androgen effect
Increase in oestrogen effect
What can gynaecomastia mimic?
Male breast cancer, especially if unilateral
Does gynaecomastia cause an increase risk of cancer?
No
Why does gynaecomastia occur in most neonates?
Secondary to circulating maternal and placental oestrogens and progesterone
How common is transient gyanecomatia in puberty?
Affects more than half of boys
What causes transient gynaecomastia in puberty?
Oestrogen production peaks earlier than testosterone
What are the pathological causes of gynaecomastia?
Klinefelter’s syndrome
Oestrogen excess
Gonadotrophin excess
Drug related
What are the pathological causes of oestrogen excess?
Cirrhosis of the liver
Why does cirrhosis of the liver cause oestrogen excess?
Oestrogen is not metabolised effectively
What can cause gonadotrophin excess?
Functioning testicular tumours, e.g. Leydig and Sertoli cell tumours
Testicular germ cell tumours
What drugs can cause gynaecomastia?
Spironolactone Chlorpromazine Digitalis Cimetidine Alcohol Marijuana Heroin Anabolic steroid
What % of malignancies in women are accounted for by breast cancer?
About 30%
What proportion of women develop breast cancer at some point in their life?
1 in 12
What % of breast cancer cases are in males?
1%
What is the problem with male breast cancer?
It tends to present later
Why does male breast cancer tend to present later?
Don’t think they can get it
Embarassed
What increases the risk of male breast cancer?
Klinefelter’s syndrome
Male to female transexuals
Men treated with oestrogen for prostate cancer
What % of breast cancers are adenomcarcinomas?
95%
Give an example of a rare malignant tumour of the breast
Primary sarcomas such as angiosarcoma
Where are breast cancers most common?
Upper outer quadrant, towards axilla
What % of breast cancers occur in the upper outer quadrant?
Approx 50%
What are the major risk factors for breast cancer related to?
Hormone exposure
What are the risk factors for breast cancer?
Gender Uninterrupted menses Early menarche Late menopause Reproductive history Breast-feeding Obesity and high fat diet Exogenous androgens Geographic influence Atypical changes on previous biopsy Previous breast cancer Radiation Genes
When will a woman have uninterrupted menses?
Very few or no pregnancies
Didn’t breast feed
Why does uninterrupted menses increase in risk of breast cancer?
During menstrual cycle, turnover of cels - more mitoses and mutations
What age of menarche increases risk of breast cancer?
<11 years
What aspects of reproductive history are related to risk of breast cancer?
Parity
Age at first full term pregnancy
Why does obesity and a high fat diet increase risk of breast cancer?
Androgens are converted to oestrogens in peripheral adipose tissue
Where may exogenous oestrogens come from?
HRT slightly increases risk
Long term users of OCP possibly have an increased risk
By how much is risk of breast cancer increased with HRT?
1.2-1.7 times
What countries have a higher incidence of breast cancer?
US and Europe
What are the possible explantations for the geographical influence of breast cancer?
Diet
Physical activity
Breast-feeding
Environmental factors
By how much does atypical changes in previous biopsy increase the risk of breast cancer?
4-5 times
By how much does previous breast cancer increase the risk of breast cancer?
10x
How is radiation related to breast cancer risk?
Increased risk with previous exposure to therapeutic radiation, especially in childhood and adolesence
Give an example of when radiation may increase risk of breast cancer?
Mantle radiation for Hodgkin’s lymphoma
What % of breast cancers are hereditary?
10%
What % of breast cancers are attributed to BRCA1 and BRCA1 genes?
3% of all, 25% of familial
What do BRCA1 and BRCA2 do?
Tumour suppressor genes - their proteins repair damaged DNA
What % of the population have BRCA1 germline mutations?
0.1%
What is the lifetime risk of breast cancer of female carriers of BRCA1 or 2 genes?
85%
What happens to the median age of diagnosis when a woman has a mutation in BRCA1 or 2?
It decreases by 20 years
What may carriers of the BRCA1 or 2 gene choose to do?
Undergo prophylatic bilateral mastectomies
Other than BRCA genes, what other gene is involved in hereditary breast cancer?
P53 (Li-Fraumeni syndrome)
What are breast carcinomas classified into?
In situ
Invasive
Where can breast carcinomas involve?
Ducts
Lobules
What happens in an in situ carcinoma?
Neoplastic population of cells limited to ducts and lobules by basement membrane, and so myoepithelial cells are preserved
What is the result of the limitation of neoplastic cells in in situ breast carcinoma?
It does not invade into vessels, and therefore cannot metastasise and kill
How does ductal carcinoma in situ most often present?
As mammographic calcifications, but can present as mass
How to the mammographic calcifications appear with DCIS?
Clusters or linear and branching
How extensive is DCIS?
Can spread through ducts and lobules, and be very extensive
How does DCIS appear histologically?
Often shows central (comedo) necrosis with calcification
What % of DCIS become invasive cancer?
50%
What is Paget’s disease?
Condition related to DCIS, where cells can extend to the nipple skin without crossing the BM
What are the symptoms of Paget’s disease?
Unilateral red and crusting nipple
What should be done when a patient presents with eczematous or inflammatory conditions of the nipple?
Should be regarded as suspicious and a biopsy performed to exclude Paget’s disease
What is the difference between DCIS and an invasive carcinoma?
Invasive has invaded beyond BM into stroma, and can invade into vessels
What is the result of invasive carcinoma being able to invade into vessels?
Can metastasise to lymph nodes and other sides
How does invasive breast carcinoma usually present?
Mammographic abnormality or mass
What is the problem with detection of invasive breast carcinoma with a mass?
By the time a cancer is palpable, more than half of patients will have axillary lymph node mets
What is peau d’orange?
The involvement of the lymphatic drainage of the skin in invasive carcinoma
What happens in peau d’orange?
There is disruption of lymphatic drainage, and so the skin becomes oedematous, so swells, but the hair follicles are tethered and pulled down into the breast
What causes a retracted nipple in invasive carcinoma?
The tumour causes tethering
What are the types of invasive breast carcinoma?
Invasive ductal carcinoma, no special type (IDC NST)
Invasive lobular carcinoma
Tubular
Mucinous
What % of invasive breast carcinomas are IDC NST?
70-80%
What are the different types of IDC NST?
Well-differentiated type
Poorly differentiated type
What is the histological appearance of the well differentiated type of IDC NST?
Tubules lined by atypical cells
What is the histological appearance of the poorly differentiated type of IDC NST?
Sheets of pleomorphic cels
What is the 10 year survival of IDC NST?
35-50%
What % of invasive carcinomas are invasive lobular carcinoma?
5-15%
What is the histological appearance of invasive lobular carcinoma?
Infiltrating cells in a single file, cells lack cohesion
Why do cells lack cohesion in invasive lobular carcinoma?
No longer have E-cadherin, so have lost links
What is the 10 year survival of invasive lobular carcinoma?
Similar to IDC NST
What % of invasive breast carcinomas are tubular?
1-2%
What is the prognosis of tubular invasive carcinoma?
Excellent
What % of invasive breast carcinomas are mucinous?
1-6%
What is the prognosis of mucinous breast carcinoma?
Excellent
Who is often affected by mucinous breast carcinoma?
Older women
Where may breast cancer metastasise to?
Lymph nodes via lymphatics
Distant metastases via blood vessels
Invasive lobular carcinoma can spread to odd sites
Where does breast cancer usually spread by lymphatics?
To the ipsilateral (same side) axilla
Where does breast cancer metastasise by blood vessels?
Bones (most frequent site)
Lungs
Liver
Brain
What sites can invasive lobular carcinoma spread to>
Peritoneum Retroperitoneum Leptomeninges Gastrointestinal tract Ovaries Uterus
What factors determine prognosis in breast cancer?
In situ disease of invasive carcinoma Histological subtype Tumour grade Tumour stage Gene expression profile
What histological subtype of breast cancer has the poorest prognosis?
IDC NST
What factors are considered in tumour stage?
Size
Locally advanced disease
Lymph node metastases
Distant mets
What is meant by locally advanced disease in cancer?
Invading into skin or skeletal muscle
How are gene expression patterns useful in breast cancer?
Microarrays have been used to examine the expression patterns of some 25,000 genes in tissues from breast cancer patients.
Computer cluster analysis of the patterns led to the identification of about 17 marker genes that can correctly identify about 90% of women who would eventually develop mets, and therefore guides what treatment they should get
How is breast cancer investigated?
Clinically
Radiographic imaging
Pathology
How is breast cancer investigated clinically?
History
Family history
Examination
How is breast cancer investigated radiographically?
Mammogram
Ultrasound scan
How is breast cancer investigated by pathology?
Fine needle aspiration cytology
Core biopsy
When was mammographic screening started in the UK?
Late 1980s
What happens in the mammographic screening programme in the UK?
Women 47-73 have 2 view mammograms every 3 years
What is the aim of mammographic screening?
Detect small impalpable cancers and pre-invasive cancer
How has mammographic screening changed the incidence of DCIS?
Increased from 5% of breast cancers to 25% in screened populations
What is looked for on mammographic screening?
Asymmetrical densities
Parenchymal deformities
Calcifications
What happens when an abnormality is found on breast cancer screening?
Assessed with further imaging - FNAC and core biopsy
What are the therapeutical approaches in breast cancer?
Local and regional control
Systemic control
How is breast cancer controlled locally and regionally?
Breast surgery
Axillary surgery
Post-operative radiotherapy
What are the types of breast surgery in control of cancer?
Mastectomy
Breast conserving therapy
What does the decision regarding mastectomy or breast conserving surgery depend on?
Patient choice
Size and site of tumour
Number of tumours
Size of breast
What does the extent of axillary surgery depend on in breast cancer?
Whether there are involved nodes
What are the types of axillary surgery in the control of breast cancer?
Sentinel node sampling
Axillary dissection
What is the advantage of sentinel lymph node biopsy?
Reduces risk of postoperative morbidity
What happens in a sentinel lymph node biopsy?
Intraoperative lymphatic mapping with dye and/or radioactivity of the draining or ‘sentinel’ lymph node(s) - the one most likely to contain breast cancer mets/
If sentinel node is negative, axillary dissection can be avoided
How is systemic control of breast cancer achieved?
Chemotherapy
Hormonal treatment
Herceptin treatment
When is chemotherapy given as a neoadjuvant (before surgery)
If the benefits outweigh the risks
Give an example of a hormonal treatment for breast cancer?
Tamoxifen
What does hormonal treatment for breast cancer depend on?
Oestrogen receptor status
What % of breast cancers are ER positive, and so can have endocrine therapy?
80%
What does herceptin treatment depend on?
Her2 receptor status
What % of cancers are Her2 positive?
20%
What is Her2?
A member of the human epidermal growth factor receptor family that encodes a transmembrane tyrosine kinase receptor
What is herceptin?
Humanised monoclonal antibodies against the Her2 protein
How can survival from breast cancer be improved?
Early detection Neoadjuvant chemotherapy Use of newer therapies e.g. Herceptin Gene expression profiles Prevention of familial cases
How can early detection of breast cancer be achieved?
Awareness of disease
Importance of family history
Self-examination
Mammographic screening
What is the purpose of neoadjuvant chemotherapy?
Early treatment of metastatic disease
How can familial cases of breast cancer be prevented?
Genetic screening
Prophylactic mastectomies