Session 7

Question 1

CLINICAL PRESENTING FEATURES

Of breast disease

Answer 1

Physiological swelling and tenderness.
Nodularity.
Breast pain (not usually associated with malignancy)
Palpable breast lumps.
Nipple discharge including galactorrhoea.
Breast infection and inflammation - usually associated with lactation.

Question 2

Physiological swelling and tenderness

Answer 2

• Puberty • Breast enlargement, sometimes initially unilateral, is the first
obvious sign of puberty in girls. Breast buds may initially be
unilateral. Pubertal breast development is known as thelarche.

Question 3

What is the most common benign breast disorder?

Answer 3

Fibrocystic change is the most common benign
breast disorder.
This usually affects women aged 20-50 and appears to be hormonal in aetiology. Not often presents with pain and modularity.

Question 4

NODULARITY

Answer 4

• The symptoms are greatest about one
week before menstruation and decrease
when it starts.
• Examination may reveal an area of
nodularity or thickening, poorly
differentiated from the surrounding tissue
and often in the upper outer quadrant of
the breast.
• If the changes are bilaterally symmetrical,
they are rarely pathological. If there is
asymmetry it is acceptable to review the
patient after one of two menstrual cycles,
seeing her mid-cycle.

Question 5

Cyclical mastalgia

Answer 5

The breasts are active organs that change throughout the menstrual cycle and some degree of tenderness and nodularity in the premenstrual phase is so common that it may be considered as normal, affecting up to two thirds of all menstruating women. It rapidly resolves as menstruation starts.

Question 6

Palpable benign breast lumps

Answer 6

Most benign lumps will be either cysts or fibroadenomas. A benign mass is usually three-dimensional, mobile and smooth, has regular borders and is solid or cystic in consistency.

Question 7

Breast cysts and Treatment for breast cysts?

Answer 7

• Cysts are most common between the ages of 35 and 50. They are
palpable as discrete lumps and may be recurrent. They cannot be
reliably distinguished from solid tumours on clinical examination
.
Identify cyst with palpating and drain with needle and syringe.

Question 8

Fibroadenomas

Answer 8

• These are benign tumours that are common in young women, with
incidence peaking at 20-24 years of age. • They are the most common type of breast lesion. • Fibroadenomas arise in breast lobules and are composed of fibrous
and epithelial tissue. They present as firm, non-tender, highly
mobile palpable lumps. Hormones seem to be involved in
aetiology, and hormone replacement therapy (HRT) increases the
incidence.

Question 9

Intraductal Papilloma

Answer 9

Each breast has multiple milk ducts that converge into an outlet in the nipple. Pathology can only be confined to one nipple. If blocked can become engorged, painful and susceptible to infection.
Insert image

Question 10

Mammary duct ectasia

Answer 10

Unknown aetiology
- dilation of major ducts, filled with creamy secretion with periodical inflammation - May be asymptomatic or nipple discharge, (bloody, serous, creamy white or yellow - retracted nipple - Acute inflammation - recurrent common infection.
Treatment : surgical excision of the major duct, correction of nipple retraction.

Question 11

Breast infections

Answer 11

Mastitis
Generalised cellulitis of the breast
Treated with antibiotics.

Breast abscesses.
Present with point tenderness, erythema, and fever.
Generally related to lactation
Non-lactational abscesses more frequent in smokers.
Caused by staph (usually require I &D) or strep (often more diffuse, superficial infection treated with local wound care and abx)

Question 12

Periductal mastitis

Answer 12

Panopto

Question 13

Referral

Answer 13

• Refer people via the suspected cancer pathway referral (to be seen
within two weeks) to a specialist breast clinic if they are: • Aged ≥30 and have an unexplained breast lump with or without pain; or •
Enlarged axillary lymph nodes. Aged ≥50 with any of the following symptoms in one nipple only: • Discharge • Retraction • Other changes of concern
• Consider a suspected cancer pathway
referral (for an appointment within 2
weeks) people: • With skin changes that suggest breast
cancer or • Aged 30 and over with an unexplained
lump in the axilla (new NICE
recommendation for 2015).
Consider non-urgent referral in people aged under 30 with an
unexplained breast lump with or without pain (new NICE
recommendation for 2015).

Question 14

Describe stages of grief

Answer 14

Insert image

Question 15

What does normal breast tissue look like histologically?

Answer 15

Insert slide

Question 16

What physiological changes are seen in breast tissue?

Answer 16

• 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
seen in breast tissue?
• 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)

Question 17

What does breast tissue look like in pregnancy?

Answer 17

Insert slide

Question 18

How can breast conditions present?

Answer 18

• Pain • Palpable mass • Nipple discharge • Skin changes • Lumpiness
• Mammographic abnormalities

Question 19

Which breast conditions cause pain?

Answer 19

• May be cyclical and diffuse, in which case
often physiological • Non-cyclical and focal – ruptured cysts,
injury, inflammation • Occasionally presenting complaint in
breast cancer

Question 20

Which breast conditions cause a palpable mass?

Answer 20

• Causes include:
– Normal nodularity
– Invasive carcinomas
– Fibroadenomas
– Cysts • Most worrying if hard, craggy and fixed • No woman should be allowed to have a
lump in the breast without a firm diagnosis

Question 21

Which breast conditions cause mammographic abnormalities?

Answer 21

• Worrying findings include densities and
calcifications
– Densities – invasive carcinomas, fibroadenomas,
cysts – Calcifications – ductal carcinoma in situ (DCIS),
benign changes
• Found during mammographic screening • Women between 47-73 years invited every 3
years • Easier to detect lesions in breasts of older
women

Question 22

Are breast conditions common?

Answer 22

• 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

Question 23

What are the common breast condition?

Answer 23

• Fibroadenomas
– Can occur at any age during reproductive
period – Often <30 years
• Phyllodes tumours
– Most present in 6th decade
• 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

Question 24

How do we classify pathological conditions of the breast?

Answer 24

• Disorders of development • Inflammatory conditions • Benign epithelial lesions • Stromal tumours • Gynaecomastia • Breast carcinoma

Question 25

What inflammatory conditions can be Seen in the breasts?

Answer 25

• 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
• Fat necrosis
– Presents as a mass, skin changes or
mammographic abnormality – Often history of trauma or surgery – Can mimic carcinoma clinically and
mammographically

Question 26

What benign epithelial lesions can be seen in the breasts?

Answer 26

• 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

Question 27

What stromal tumours can be seen in the breasts?

Answer 27

• Stromal tumours – e.g., fibroadenoma, phyllodes tumours,
lipoma, leiomyoma, hamartoma • Fibroadenomas
– 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 – Histology - composed of a mixture of stromal and epithelial
elements – Can mimic carcinoma clinically and mammographically – Localised hyperplasia rather than true neoplasm

Question 28

What is gynaecomastia?

Answer 28

• 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

Question 29

What causes gynaecomastia?

Answer 29

– Occurs in most neonates secondary to
circulating maternal and placental oestrogens
and progesterone
– Transient gynaecomastia affects more than
half of boys in puberty as oestrogen production
peaks earlier than that of testosterone – Klinefelter’s syndrome
– Oestrogen excess - cirrhosis of the liver (when
oestrogen not metabolised effectively) – Gonadotrophin excess - functioning testicular
tumour, e.g., Leydig and Sertoli cell tumours,
testicular germ cell tumours
– Drug-related – spironolactone, chlorpromazine,
digitalis, cimetidine, alcohol, marijuana,
heroin , anabolic steroids

Question 30

How common is breast cancer?

Answer 30

• Most common cancer in the UK • 1 in 7 women will develop breast cancer at some time
in their life • Male breast cancer
• Approximately 95% are adenocarcinomas • Other malignant tumours of the breast are very rare,
e.g., primary sarcomas such as angiosarcoma • Most common in the upper outer quadrant
(approximately 50% occur here)
– 1% of all cases of breast cancer – Increased risk with Klinefelter’s syndrome, male to
female transsexuals, men treated with oestrogen for
prostate cancer

Question 31

What are the risk factors for breast cancer

Answer 31

• Major risk factors are related to hormone
exposure
– Gender – Uninterrupted menses – Early menarche (< 11 years) – Late menopause – Reproductive history - parity and age at first
full term pregnancy – Breast-feeding – Obesity and high fat diet – Exogenous oestrogens – HRT slightly increases
risk (1.2-1.7 times), long term users of OCP
possibly have an increased risk – Breast density
• Geographic influence
– Higher incidence in US and Europe
– Possible explanations include diet, physical activity,
breast-feeding, environmental factors, alcohol consumption
• Atypical changes on previous biopsy (4-5 times) • Previous breast cancer (10 times) • Radiation
– Increased risk with previous exposure to therapeutic
radiation (especially in childhood or adolescence), e.g. mantle radiation for Hodgkin’s lymphoma
• 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 BRCA2
• Both tumour suppressor genes – their proteins repair
damaged 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 than sporadic cases • Carriers may undergo prophylactic mastectomies
– Another gene involved in hereditary breast
cancer is p53 (Li-Fraumeni syndrome)

Question 32

How do we classify breast carcinoma?

Answer 32

• Carcinomas divided into in situ and

invasive • Carcinomas can be ductal or lobular

Question 33

What is in situ carcinoma?

Why is ductal carcinoma in situ (DCIS) a problem?

Answer 33

• 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 metastasise or kill
the patient
• Non-obligate precursor of invasive
carcinoma • 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

Question 34

What is Paget’s disease?

Answer 34

• 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

Question 35

How does invasive carcinoma differ from DCIS?

Answer 35

differ from DCIS?
• Neoplastic cells have 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 – involvment of lymphatic
drainage of skin

Question 36

How is invasive breast carcinoma classified?

Yeah Yeah

Answer 36

• Invasive ductal carcinoma, no special type (IDC NST)
– 70-80%
– Well-differentiated type – tubules 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)

Question 37

How does breast cancer spread?

Answer 37

• 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

Question 38

What factors determine prognosis in breast cancer?

Answer 38

• In situ disease or invasive carcinoma • Tumour stage:
– Tumour size and locally advanced disease – invading
into skin or skeletal muscle – Lymph Node metastases – Distant Metastases
• Tumour grade
• Histologic subtype – IDC NST has poorer prognosis
• Molecular classification and gene expression
profile

Question 39

What is molecular classification in breast cancer?

Answer 39

Insert slide and use panopto

Question 40

What is a gene expression profile and why is it important in breast cancer?

Answer 40

• 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 metastases.

Question 41

How do we investigate and diagnose breast cancer?

Answer 41

• Triple approach
– Clinical – history, family history, examination
– Radiographic imaging – mammogram and
ultrasound scan – Pathology – core biopsy and fine needle
aspiration cytology (FNAC)

Question 42

What is mammographic screening?

Answer 42

• Started in the UK in the late 1980s • Women 47–73 years • 2 view mammograms every 3 years • Aim is to detect small impalpable cancers and pre-invasive cancer
(incidence of DCIS has increased from 5% of breast cancers to 25% in
screened populations) • Look for asymmetric densities, parenchymal deformities,
calcifications • Assess abnormalities using further imaging, core biopsy and FNAC

Question 43

What are the therapeutic approaches in breast cancer?

Answer 43

• Local and regional control
– Breast surgery – mastectomy or breast
conserving surgery – decision depends on patient choice, size and site of tumour, number of tumours, size of breast
– Axillary surgery – extent depending on
axilla
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, e.g. tamoxifen – depending
on oestrogen receptor status (approximately 80% of
cancers are ER positive) – Herceptin treatment – depending on Her2 receptor
status (approximately 20% of cancers are Her2
positive)
• Her2 is a member of the human epidermal
growth factor receptor family • Encodes a transmembrane tyrosine kinase
receptor • Herceptin = trastuzumab = humanised
monoclonal antibodies against the Her2 protein

Question 44

What is sentinel lymph node biopsy?

Answer 44

• Reduces the risk of postoperative
morbidity • Intraoperative lymphatic mapping with
dye and/or radioactivity of the draining
or ‘sentinel’ lymph node(s) – the one
most likely to contain breast cancer
metastases • If the sentinel node(s) is negative axillary
dissection can be avoided

Question 45

How do we improve survival from breast cancer?

Answer 45

• 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