Week 7 Flashcards
How many secretory lobules make the secretory tissue in the breast?
15-25
What are Cooper’s suspensory ligaments and why are they important clinically?
Condensations of connective tissue in the breast that form septa
Extend from the dermis of the skin to the deep fascia overlying the muscle of the anterior chest wall
Clinically important because if a mass grows within the breast, this may cause the breast to “pucker” at a certain point, reminiscent of the peel of an orange (peau d’orange)
What is the name of the basic functional secretory unit of the breast?
What is it made up of?
The terminal duct lobular unit (TDLU)
Made up of the lobule and the extralobular terminal duct
What type of cells surround the secretory cells of the acinus (cluster of cells that represents a berry)?
What, in turn, surrounds these cells?
Myoepithelial cells surround the acinar cells, which are in turn surrounded by the basal lamina
What types of cells line the acini?
What type of cells line the inside of larger ducts, such as a lactiferous duct?
Secretory epithelial cells line the inside of the acini and can be either columnar or cuboidal
The epithelium lining the inside of ducts also varies from a thin stratified squamous epithelium to stratified cuboidal epithelium
What other tissue type resembles breast lobules, and many believe is the evolutionary source of mammory glands?
Sweat glands
Describe the structure of the nipple
Lined by a thin, highly pigmented keratinised stratified squamous epithelium
Core of dense irregular connective tissue mixed with bundles of smooth muscle fibres (allows for nipple erection)
Core also contains lactiferous ducts, each serving one lobe of the breast
Several sebaceous glands are also present and end directly on the surface of the skin (Montgomery glands - somewhere between being milk-producing and sweat-producing), function to keep the areola and the nipple lubricated
How does the breast change in the luteal phase?
The epithelial cells increase in height
The lumina of the ducts becomes enlarged
Small amounts of secretions begin to appear in the ducts
What dramatic changes occur in the breast following pregnancy?
Think 1st, 2nd and 3rd trimester
Which hormones cause this?
1st trimester - elongation and branching of the smaller ducts, as well as proliferation of the epithelial cells and myoepithelial cells
2nd trimester - development of glandular tissue and differentiation of secretory alveoli. Plasma cells and lymphocytes also penetrate nearby connective tissue
3rd trimester - maturation of secretory alveoli, development and maturation of rough ER
Connective tissue and adipose tissue amounts decrease
These changes are caused by oestrogen and progesterone
Describe the composition of human breast milk
How does this differ to cow’s milk?
Approximately…
88% water
1.5% protein (mostly lactalbumin and casein)
7% carbohydrate (mainly lactose)
3.5% lipid
Small amounts of ions, vitamins and IgA
Cow’s milk has a much higher % of casein
Lipid secretions of breast milk are secreted by ____
Proteins in breast milk are secreted by ____
Lipids are secreted by eccrine secretion
Proteins are secreted by merocrine secretion
How does the mammary gland change following menopause?
Secretory cells of the TLDUs (terminal ductal lobular units) degenerate leaving only the ducts
Fewer fibroblasts and reduced collagen/elastic fibres in the connective tissue
What cell type in the breast appears to be the most common site for breast cancer?
Ductal cells (forming ductal carcinoma)
What are the components of the ‘triple assessment’ when assessing breast disease?
Clinical
- history
- examination
Imaging
- mammography
- USS
- MRI
Pathology
- cytopathology
- histopathology
How is breast disease classified…
a) by cytopathology
b) by histopathology?
What is the key difference?
a) cytopathology
- C1 - unsatisfactory
- C2 - benign
- C3 - atypia, but probably benign
- C4 - suspicious of malignancy
- C5 - malignant
b) histopathology
- B1 - unsatisfactory/normal
- B2 - benign
- B3 - atypia, but probably benign
- B4 - suspicious of malignancy
- B5 - malignant
- 5a - carcinoma in situ
- 5b - invasive carcinoma
Key difference is histopathology outlines if disease is confined or if it has started to spread
Ducts are continuous with the nipple and external skin. As such, how might ductal carcinoma initially present?
What is this called?
May present with blood/discharge or dry skin/eczema
If dry skin/eczema is seen, this is Paget’s Disease of the Breast
Name some non-neoplastic forms of breast disease
Gynaecomastia
Fibrocystic change
Hamartoma
Fibroadenoma a.k.a. breast mouse
Sclerosing lesions (sclerosing adenosis, radial scar/CSL)
Lipoma
Name some inflammatory forms of breast disease
Fat necrosis
Duct ectasia
Acute mastitis/abscess
What are the two forms of benign breast tumour?
Phyllodes tumour
Intraduct papilloma (most common cause of bloody nipple discharge)
Importantly, while both are considered to be benign, they exist on a spectrum and have the potential to become malignant
In gynaecomastia, what type of growth is seen?
What are some of the associated risk factors for developing this condition?
Ductal growth is seen without lobular development
Risk factors - exogenous/endogenous hormones, cannabis, prescription drigs, liver disease (causing raised oestrogen)
What is fibrocystic change?
How common is it and in what age group is it seen?
Development of ‘lumpy’ or ‘doughy’ areas within the breast that may be cystic or solid
Very common, and is seen in women aged 20-50
May be associated with some pain, and can also be seen to be worse around menstruation
What are the risk factors for developing fibrocystic change in breasts?
Anything that involves more time ovulating
Early menarche
Late menopause - condition usually resolves following menopause
Menstrual abnormalities
NB - these are also risk factors for breast cancer!
What is a hamartoma?
Circumscribed lesion composed of cell types normal to the breast, but present in abnormal proportion or distribution
What is a fibroadenoma also referred to?
Are they common?
Which group experiences these more frequently?
Fibromadenomas also called “breast mouse”
Very common and usually solitary
More common in African women
How would a fibroadenoma be described in terms of palpation?
Circumscribed
Rubbery
Painless, firm, discrete mobile mass
What is the size cut-off for a fibroadenoma to be excised via vacuum biopsy?
2cm - if greater than 2cm, has to be removed via surgical excision
What are sclerosing lesions of the breast?
What are the two main types?
Benign disorderly proliferation of acini and stroma that may cause mass or calcification. Usually asymptomatic but may cause pain or tenderness. Most common in women in their 30s and 40s but can occur anywhere from 20s-70s
- Sclerosing adenosis
- Radial scar/complex sclerosing lesion
What is the size cut-off at which point a radial scar becomes a complex sclerosing lesion?
Radial scars - 1-9mm
Complex sclerosing lesions - >10mm
What causes fat necrosis of the breast?
What is seen on histology?
Fat necrosis is caused by trauma (seatbelts, dogs etc.) or warfarin therapy
Damage and disruption of adipocytes, causing inflammation of acute inflammatory cells. On histology, foamy macrophages are seen with subsequent fibrosis and scarring
What’s the diagnosis?…
- Pain and acute episodic inflammatory changes
- Bloody and/or purulent discharge
- Possible nipple retraction and distortion
- Formation of fistulae
- Associated with smoking
Duct ectasia
- sub-areolar duct dilatation
- periductal inflammation and fibrosis
- resultabt scarring and fibrosis
How is duct ectasia managed?
Treat any acute infections
Exclude malignancy
Stop smoking
Excise ducts
What are the two main causes of acute mastitis/abscess formation in the breast?
Duct ectasia
- mixed organisms
- anaerobes
Lactation
- Staph aureus (most common)
- Strep pyogenes
How is acute mastitis/breast abscess managed clinically?
Antibiotics and treatment of underlying cause
Percutaneous drainage
Incision and drainage
If resistant to treatment, what could acute mastitis develop into?
Inflammatory breast cancer
Name 2 benign breast tumours
Phyllodes tumour
Intraduct papilloma
NB - these both have the potential to become malignant, it’s just rare
What would be the most likely benign breast tumour if it was seen in a woman aged..
- 40-50
- 35-60
40-50 - Phyllodes tumour
35-60 - Intraduct papilloma (may also show nipple discharge +/- blood)
What is the investigation of choice for possible breast disease in women a) under 40 and b) over 40?
a) under 40 - USS
b) over 40 - mammography
What are some of the maternal benefits of breast feeding?
Weight loss
Protective against breast and ovarian cancers
Acts as natural contraceptive for the first 3 weeks following delivery
When performing a breast exam, what are the 3 ways you would ask a patient to present themselves?
- first, hands down by sides, relaxed and neutral
- arms raised to the ceiling to see if any puckering of skin
- press hands on hips to contract pec major
Describe the let down reflex
- baby suckling triggers mechanoreceptors in nipple, which act on higher brain centres via ascending sensory information. Higher brain centres are also triggered by the sound of the baby’s cry
- Hypothalamus signals anterior pituitary to release prolactin and posterior pituitary to release oxytocin
- Prolactin causes milk secretion
- Oxytocin causes smooth muscle contraction
What do the RCOG Green-Top guidelines state with regards to the following during pregnancy?
- Surgery
- Chemotherapy
- Radiotherapy
Surgery - can be performed at any time, either breast conserving or full mastectomy
Radiotherapy - must be avoided throughout pregnancy
Chemotherapy - must be avoided throughout the FIRST trimester. NB - tamoxifen and trasuzuman cannot be used at ANY point
What metastatic tumours are seen to spread to breast?
Bronchial carcinomas
Ovarian serous carcinomas
Clear cell carcinomas of the kidney
Malignant melanoma
Soft tissue tumours e.g. leiomyosacroma
What are the two main classifications of breast carcinoma?
Ductal
Lobular
Lobular in situ neoplasia has 2 historic entities, dependent on the amount of the lobule involved. What are these two entities, and what is the % cut-off?
If <50% of lobule involved - Atypical Lobular Hyperplasia (ALH)
If >50% of lobule involved - Lobular Carcinoma in Situ (LCIS)
What is the genetic expression seen in lobular neoplasias in situ?
ER (oestrogen receptor) positive
E-cadherin negative (deletion and mutation of CDH1 gene on chromosome 16q22.1)
Lobular in situ neoplasia has an incidence of 0.5-4% in benign biopsies, is not palpable or visible grossly, and is usually an incidental finding. What, then, is the significance of its detection?
15-20% of cases have a higher grade lesion elsewhere on open biopsy e.g. DCIS
Also 8x relative risk of becoming subsequent invasive carcinoma
Intraductal proliferation can be classified into 4 separate forms - what are they, and what is the risk of each going on to become invasive ductal carcinoma?
- Epithelial hyperplasia of usual type - 2x risk
- Columnar cell changes
- Atypical ductal hyperplasia - 4x risk
- Ductal carcinoma in situ (low grade) - 10x risk
Where in the breast does ductal carcinoma in situ arise?
What % of breast malignancies are DCIS?
What feature of DCIS’ typical appearance means that surgery is usually the go-to option?
DCIS arises in the terminal duct lobular units (TDLUs)
15-20% of breast malignancies are DCIS
DCIS tends to be unifocal meaning surgical treatment is usually opted for
Paget’s disease of the nipple is invasive/non-invasive
Still non-invasive, as the cancer is still confined to the epithelial cells of the basement membrane and has travelled along the epidermis to reach the nipple
The purpose of breast screening is to mainly catch breast cancers at what stage?
Low Grade DCIS as these will go on to become High Grade
How common is breast cancer?
Most common cancer in women and the second most common cause of cancer death in women
Most common form of cancer (with prostate being the most common in men)
1 in 8 will develop breast cancer
What are some of the risk factors for developing breast cancer?
Increasing age
More menstrual cycles - young at menarche, late menopause, nullparity, never breastfeeding (having children and breastfeeding are protective)
Hormones - endogenous, exogenous (OCP, HRT)
Previous breast disease
Lifestyle - obesity, alcohol consumption, poor diet, NSAIDs, smoking
Genetics - BRCA1, BRCA2, TP53, PTEN
Are the oral contraceptive pill and hormone replacement therapy significant factors in the development of breast cancer?
Not massively, increased risk is probably quite small
Balance risk of using vs risk of pregnancy/effects of menopause
What % of the population carry either a BRCA1 or BRCA2 mutation?
What is the lifetime risk of these people developing breast cancer?
0.1% of the ppn carry mutation
BRCA1 and BRCA2 mutations are seen in 2% of all breast cancers. Carry a lifetime risk of 45-64%
What is the 1 year, 5 year and 10 year survival % of breast cancer?
1 year - 96%
5 year - 87%
10 year - 78%
What are the 3 parameters that breast cancer can be classified on?
Morphology - stage (anatomical descriptor) and grade (degree of differentiation, gives prognosis)
Gene expression profiling
Hormone receptor expression - ER, PR, HER2
What are the 3 criteria that breast carcinoma can be graded on?
What are the min and max scores?
- Tubular differentiation (1-3)
- Nuclear pleomorphism (1-3)
- Mitotic activity (1-3)
Min score = 3 (good), max score = 9 (bad)
Score 3, 4 or 5 = Grade 1
Score 6 or 7 = Grade 2
Score 8 or 9 = Grade 3
Breast cancers can be classified based on gene expression profiling. What are some of these subtypes?
Basal-like - ER-, HER2-, Basal CK+
HER2 - ER-, HER2+
Normal breast-like - ER-, non-epithelial
Luminal A - ER+, low proliferation
Luminal B - ER+, high proliferation
Luminal C - ER+, high proliferation
Breast cancers can also be classified based on the hormone receptors they express.
What % of breast cancers express a) oestrogen receptors, b) progesterone receptors and c) HER2 receptors?
ER - 80% positive
PgR - 67% positive
HER2 - 14% positive
For a breast cancer that expresses oestrogen receptors, what treatment options are available?
Oophrectomy
Tamoxifen (selective oestrogen receptor modulator - prodrug, the active forms of which competitively bind ERs and prevent oestrogen from doing so)
Aromatase inhibitors (Letrozole) - only effective in post-menopausal women in which oestrogen is being produced by peripheral tissues. Prevents aromatase from producing oestrogens by competitively reversibly binding to the haem of the CYP450
GnRH antagonists (Goserilin) - causes down-regulation of oestrogen and testosterone production after initially causing a rise. Takes 14-21 days to work
What medication can be used in HER2+ breast cancers?
Trastuzumab (Herceptin)
Based on hormone receptor profiles, which breast cancers have the worst prognosis?
ER-, PgR-, HER2+
‘Triple Negatives’
What scoring tool is used to predict breast cancer prognosis?
Formerly the Nottingham Prognostic Index, now PREDICT
Combines histopathology, ER, clinical factors, HER2 and mode of detection
What are some of the overt physical symptoms of breast cancer?
Dimpled or depressed skin
Visible lump
Nipple changes including inversion
Bloody discharge
Texture change
Colour change
What types of breast conserving surgery are there?
“Lumpectomy” a.k.a. wide local excision
Wire guided local excision
Oncoplastic breast conservation including therapeutic mammoplasty
How does breast conservation + radiotherapy compare to mastectomy in terms of effectiveness?
Breast conservation + radiotherapy is at least as good as mastectomy and may have better outcomes
However, ultimately it should be the patient’s choice
How is a wide local excision performed?
Aim for a 1cm excision at all margins
Perform “full thickness” excision at the anterior and posterior margins
Follow up with radiotherapy
What can be done to aid in the excision of a non-palpable breast lump?
Wiring (done during mammography)
What neoadjuvant treatments can be given to treat breast cancers?
What is the aim?
Chemotherapy (FEC100 and taxane) +/- Herceptin
Aromatase inhibitors (Letrozole) - reserved for post-menopausal women
These treatments aim to shrink the tumour in size, meaning that breast conserving surgery can become an option again
What are some of the reconstructive options when performing a mastectomy?
External prosthesis
Implant only (+/- autologous cellular matrix)
Latissimus dorsi pedicled flap (LD flap) +/- implant
Deep Inferior Epigastric artery perforator (DIEP) free flap
Inferior (or superior) gluteal artery perforator (IGAP) free flap
Also: TUG flap, PAP free flap, SGAP flap
What other surgery is always performed when doing breast surgery?
Axillary surgery
- preoperative axillary staging: USS axilla +/- core biopsy
Sentinel node biopsy
Axillary clearance
Axillary radiotherapy
What adjuvant therapy can be given following breast surgery?
Radiotherapy - routine following WLE, reduces recurrence risk by 50%
ER blockade with 5 years of tamoxifen or aromatase inhibitors (Letrozole, reserved for post-menopausal women)
Chemotherapy - various regimes, often including anthracycline and taxane
Trastuzumab (Herceptin) - given by s/c injection, antibody against HER2 receptors which is found on 15% of breast cancers
Bisphosphonates (palliative) to reduce bone turnover rates in those with bone mets
