1. BREAST DISEASE
PATHOLOGY
Benign changes
Fibrocystic changes: cyst formation, apocrine metaplasia, duct adenosis, sclerosing adenosis
– in young females
Epithelial hyperplasia: mild, moderate, florid (florid associated with potential progression to
malignancy)
Sclerosing lymphocytic lobulitis: perivascular and perilobular chronic inflammation
associated with autoimmune disease (DM type 1) – presents as irregular mass – need a
biopsy specimen
Hamartoma: growth of a benign lesion of a particular tissue type arranged abnormally –
differential diagnosis of fibroadenoma
Duct ectasia – abnormal dilatation of ducts – if acutely inflamed and presenting as a
discharge or fistula (periductal mastitis)
Radial scar (<1 cm) or complex sclerosing lesion (>1cm) – found incidentally or stellate
lesion on mammography – can be associated with invasive or in situ carcinoma
Neoplastic breast disease
All patients identified through breast screening or symptomatic presentation – undergo
TRIPLE ASSESSMENT
i. Clinical examination,
ii. Radiology (mammography (>35yrs), Ultrasound + mammography (<35) – due to
dense breast tissue in young patients)
iii. FNAC, Core Biopsy
Benign
Fibroadenoma – well defined mobile mass in young women (biphasic lesion of epithelial
and stromal component on histology)
Intraduct papillomas comprise a frond-like epithelial proliferation within breast ducts, may
be single or multiple – most common cause of bloody nipple discharge.
Malignant carcinoma –
Most common cancer in women, 2nd largest killer of all cancers (Lung: 1st)
1 in 9 women and 1 in 300 men
Paget’s disease: eczematous lesion of the breast – underlying DCIS or invasive carcinoma
In situ or invasive – lobular often missed on mammography – often need MRI
Pure ductal carcinoma in situ (DCIS): present as breast mass, nipple discharge, Paget’s
disease of skin, skin dimpling, and peau d’orange.
WLE: surgical resection margin of 2mm
Invasive carcinoma – breast mass, nipple discharge or breast pain (15%), asymptomatic on
screening mammography; 75% ductal; conventionally invasive tubal carcinoma is better
prognosis than DCIS
Grade: morphological description of tumour (differentiation and architectural changes)
Stage: progression of tumour anatomically (depth of invasion (T), node involvement (N),
metastasis (M))

2. Size (cm): <2 (T1), 2 – 5 (T2), >5 (T3), skin, chest wall involvement (T4)
Determine prognosis using:
Nottingham prognostic index (NPI): (0.2 x tumour size (cm)) + tumour grade + tumour stage
Stage 1 – no nodes
Stage 2 – three axillary lymph nodes OR single internal mammary node
Stage 3 - ≥4 axillary nodes OR an axillary lymph node + internal mammary node
Nodes:
N0 No nodal metastases
N1 Mobile ipsilateral node(s) involved
N2 Fixed ipsilateral node(s) involved
N3 Ipsilateral internal mammary node(s) involved
Immunohistochemistry:
Determine oestrogen (ER) or progesterone (PR) receptor status – if positive (better
prognosis than negative status)
Determine c-erb-B2 (HER-2) gene over amplification or use FISH for gene overexpression:
positive (poor prognosis); negative (better prognosis)
If ER, PR negative and HER-2 positive (worse prognosis);
If no clinical or radiological (ultrasound) evidence of axillary node metastasis – do a Sentinel
lymph node biopsy
Remember breast can be involved in unusual cancer and metastases.
Phyllodes tumours: biphasic but increased stromal component (increased stromal cellularity
than fibroadenomas); tumour of young people (20-45yrs) – if benign: Wide local excision
(WLE), if malignant (mastectomy); 30% benign, 30% malignant, 40% borderline; large; rare
nodes (spread, if any, is haematogenous) – NO lymph nodes
Familial cancer: BRCA 1 (chromosome 17) and BRCA 2 (chromosome 13) and others
Both BRCA mutations – autosomal dominant but VARIABLE penetrance
BRCA 1: 80% risk breast cancer, 40% risk ovarian, Fallopian tube
BRCA 2: breast cancer, ovarian cancer – better prognosis than BRCA 1
In males BRCA 2: breast, prostate, and both can get pancreatic and malignant melanoma
Can offer Bilateral salpingo-oophorectomy (ablate ovarian cancer risk and decrease breast
cancer risk by 50%) – (can give HRT to protect against osteoporosis and heart disease) or risk
reducing mastectomy (RRM)
Others:
Li-Fraumeni syndrome (p53 mutation) – sarcomas, osteosarcomas, premenopausal breast
cancer, brain cancer
Cowden Syndrome (PTEN mutation): autosmal dominant: hamartomas in breast, skin,
thyroid, brain, endometrial, colorectal – malignant potential (most common: skin and brain)
Peutz-Jehger’s syndrome: autosomal dominant – orofacial and palm mucocutaneous
pigmentation with GI hamartomas – associated with a number of malignancies
Consider familial breast cancer in the following:
1. one first-degree relative with breast cancer diagnosed before age 40 years.

3. 2. two first- or second-degree relatives with breast cancer diagnosed before age 60
years.
3. three or more first- or second-degree relatives with breast cancer at any age.
4. a close relative with bilateral breast cancer.
5. a close male relative with breast cancer
NHS BREAST SCREENING
50-70 years 3 year mammography – if microcalcification or mass or stromal changes –
undergo triple assessment.
In familial screening – add MRI to mammography to increase sensitivity
High risk women – start at age 30 -35 years
Moderate risk women – from 40 years
Male breast cancer: invasive has worse prognosis than in situ (contrast to females) – can
also present with gynaecomastia
Other risk factors:
Anything to increase oestrogen exposure (endogenous or exogenous)
 Increasing age
 Female Sex
 Use of combined oestrogen and progesterone > 4 years (OCP or HRT)
 Nulliparous women (no pregnancy)
 Early menarche
 Late menopause
 Pregnancy after 35 years (greater risk than nulliparous)
 Obesity
 Alcohol
 Ashkenazi Jewish Ancestry
Smoking does not increase risk nor decreases it
BREAST CANCER
TRIPLE ASSESSMENT
Suspect when: hard fixed lump with skin tethering, Paget’s disease, age >30 years with
discrete lump that persists after period, unilateral skin/eczematous changes, recent nipple
distortion, nipple discharge, male >50 years with firm unilateral mass
Radiology:
Mammography: 90% sensitive in >50 years (2 views)
Ultrasound: <35 years; axillary ultrasound and guiding aspiration or biopsy
MRI: non-diagnostic mammography or young woman high risk
Core biopsy: local anaesthetic; invasive; can differentiate between in situ and invasive
cancer and provide sample for immunohistochemistry
FNAC: mostly for cyst aspiration; 20g needle to obtain cells – quick and limited in diagnosis –
no immunohistochemistry – cannot differentiate between in situ and invasive carcinoma
Failure of triple assessment mandates a surgical open biopsy: localize lesion using reidy
wire under ultrasound/xray guidance

4. Punch biopsy: Paget’s disease, local recurrence, cutaneous lesions, nipple eczema
No further tests indicated unless suspect metastasis or advanced disease at first
presentation
MANAGEMENT
Can be considered as initial; following local recurrence, and metastatic
Initial Options:
Neo-adjuvant chemotherapy
Surgery
Adjuvant radiotherapy
Adjuvant chemotherapy
Adjuvant hormonal therapy
NEO-ADJUVANT CHEMOTHERAPY: large, inflammatory, inoperable cancers
Inflammatory: oedematous and cardinal signs of inflammation but no systemic symptoms
SURGERY
Wide Local Excision (WLE): DCIS or invasive tumour <4cm – need a 2mm margin; if
removing >15% breast volume – poor cosmetic result
Mastectomy indications:
 tumour >4cm
 multifocal breast cancer
 central breast cancers
 woman does not want radiotherapy
 high risk women (familial)
 male breast cancer
 local recurrence from previous WLE
Axillary node status is the single most important prognostic indicator in breast cancer
Axillary surgery: if no clinical, radiological or pathological evidence of lymph node
involvement – offer sentinel (guardian) lymph node biopsy (SLNB) to ALL women
SLNB: based on principle that cancer drains into a chain of lymph nodes – if 1st node not
involved, then others are most likely negative – if hot/blue nodule detected – it’s positive –
offer Axillary clearance; if negative no further axillary surgery or radiotherapy required
Axillary clearance: removal of nodes (level I, II, III) around pectoralis minor –
Most important complication: arm lymphoedema (30-40%)
Breast reconstruction: immediate or late – depends on patient choice, availability of
reconstructive surgeon, adjuvant radiotherapy; generally immediate is better as skin sparing
mastectomy can be perfomed – skin provides good envelope to shape flap, is sensate and
avoids colour mismatch between different muscle flaps (dorsal, abdominal)
Nipple areolar reconstruction – late at nearly 6 months: challenging – use graft from
opposite nipple
LOCAL ADJUVANT RADIOTHERAPY:
Whole breast: all women with WLE; not usually in mastectomy unless inflammatory breast
cancer, ≥4 axillary nodes involved, involvement of skin/chest wall

5. Chest wall: ≥ 4 axillary lymph nodes, tumour >5cm, involved resection margins (i.e. not
cleared margins after resection)
Supraclavicular fossa: ≥4 axillary lymph nodes metastasis AFTER axillary clearance
SYSTEMIC
ADJUVANT CHEMOTHERAPY: anthracycline based – in intermediate or high risk women
Determining risk:
Low: Node negative AND ER/PR positive, tumour <2cm (T1), HER-2 negative, Age >35
Intermediate: Node negative AND 1 of tumour >2cm (T2), ER/PR negative, HER-2 positive,
Age < 35; OR Node positive (1-3) with ER/PR positive, HER-2 negative
High: Node positive (1-3) AND ER/PR negative, Age >50, HER-2 negative OR ≥4 axillary nodes
HORMONAL THERAPY
ER/PR positive: hormonal treatment for 5 years
Pre-menopausal: Tamoxifen (selective oestrogen receptor modulator) – if contraindicated
ovarian suppression (oophorectomy, ovarian radiotherapy, GnRH agonists)
Post-menopausal: Aromatase inhibitors (letrozole, anastrozole)
Another option: Sequential therapy – aromatase inhibitor (2-3 years) to tamoxifen (2-3
years) (total 5 years)
IF HER-2 positive:
All women following surgery and adjuvant chemo/radiotherapy should get Trastuzumab
(monoclonal antibody against HER-2 receptor)
Local Recurrence Options:
Similar as above but different indications
What is it: Recurrent malignancy in remaining breast tissue, skin or flaps; early recurrence
(<5 years) has poor prognosis
Most important factor in preventing recurrence: clear histological margins
Diagnose with triple assessment: clinical exam, radiology, ultrasound guided punch biopsy
Previous WLE and local recurrence: do a mastectomy
Previous mastectomy and local recurrence: if small: resect surgically; if large: chest wall
radiotherapy and systemic therapy
Axillary recurrence:
If no previous axillary clearance (AXL) – offer AXL now
If previous AXL: offer palliative radiotherapy/systemic therapy
Metastatic Disease:
18 – 24 months survival
Symptoms: systemic (weight loss, malaise, lethargy) and site specific (bone pain, change of
personality, breathlessness, jaundice)
Investigations:
Tumour specific: grade, stage, receptor status
Haematological and biochemistry: FBC, U&Es, LFTs, ALP, Albumin, Phosphate, Calcium
Radiology: CXR, CT Thorax, Abdomen, Pelvis (head if symptoms), Isotope bone scan,
consider PET-CT if above non-diagnostic
Aspirate relevant sites: Ascites and Pleural effusion

6. Manage: Palliative (choose least toxic regime)
1st line: endocrine and chemotherapy
Managing complications:
Bone metastases: bisphosphonates, surgical decompression (spinal cord involvement or
long bones involved), and radiotherapy in spinal metastases following surgery unless
surgery not indicated
Brain metastases: surgery if fit patient, else radiotherapy and corticosteroids
Palliative care: address (1) pain; (2) nausea and vomiting; (3) dyspnoea; (4) constipation