Breast cancer

Overview

•Most common cancer in the UK - ~55,000 new diagnoses/year; affects ~1 in 7 women
•80% of cases in women over 50; second most common cause of cancer death in women
•5-10% hereditary - most commonly BRCA1 (chromosome 17q) or BRCA2 (chromosome 13q) mutations; BRCA1 lifetime risk ~65-85%

Risk Factors

Risk factors for breast cancer
Early menarche / late menopause
Nulliparity
HRT (combined) / combined OCP
Obesity (post-menopausal)
Excess alcohol
BRCA1/2 mutation
Strong family history
Previous breast cancer (2-6x contralateral risk)
Increasing age

Presentation

•Painless breast lump - most common; hard, irregular, non-mobile (tethered)
•Skin dimpling/tethering - invasion of Cooper's ligaments causing shortening and retraction
•Peau d'orange - dermal lymphatic obstruction; oedematous pitted skin; locally advanced disease
•New nipple inversion - traction from deep tumour or periductal involvement
•Bloodstained nipple discharge - red flag; exclude malignancy (most common cause is intraductal papilloma)
•Hard, non-tender, matted axillary lymphadenopathy - suggests nodal metastasis
•Bone pain, breathlessness, jaundice, neurological symptoms - distant metastatic disease (bone, lung, liver, brain)
🚨
Inflammatory breast cancer - rapid onset red, warm, swollen breast resembling cellulitis; NO discrete lump; caused by diffuse dermal lymphatic invasion. If a woman >40 with apparent 'breast infection' does not respond to antibiotics within 1-2 weeks, urgent triple assessment is required.

Management

Managed by MDT; guided by stage, receptor status, patient fitness, and preference. Combines local (surgery + radiotherapy) with systemic treatment (endocrine, chemotherapy, targeted).

•Surgery: breast-conserving surgery or mastectomy (with immediate reconstruction option); sentinel lymph node biopsy or axillary lymph node clearance
•Radiotherapy: adjuvant after breast-conserving surgery; reduces local recurrence
•ER-positive disease (endocrine therapy):
•Pre-menopausal: tamoxifen (SERM)
•Post-menopausal: anastrozole (aromatase inhibitor) - typically 10 years
•HER2-positive disease: trastuzumab (Herceptin) - monoclonal antibody; baseline and surveillance echocardiography required (risk of cardiomyopathy)
•Triple-negative breast cancer (TNBC): chemotherapy only (no hormonal or HER2-targeted therapy); BRCA-mutated TNBC may respond to olaparib (PARP inhibitor)
•Neoadjuvant chemotherapy: used in HER2-positive, TNBC, or locally advanced disease - downstages tumour, may allow breast-conserving surgery
⚠️
Tamoxifen increases risk of endometrial cancer and VTE. Any post-menopausal bleeding in a woman on tamoxifen requires urgent investigation. Aromatase inhibitors cause bone density loss - DEXA scanning and bisphosphonates may be required.

Complications

•Lymphoedema - most common long-term morbidity after axillary lymph node dissection or radiotherapy; affects up to 20%
•Bone metastases - pathological fractures, hypercalcaemia; zoledronic acid (bisphosphonate) reduces skeletal events
•Cardiac toxicity - trastuzumab causes reversible cardiomyopathy; requires baseline and surveillance echocardiography
•Endometrial cancer - long-term tamoxifen use; investigate any post-menopausal bleeding
•Seroma - fluid collection after mastectomy/axillary surgery; usually self-resolving or aspirated

Prognosis

•Overall ~85% 10-year survival in England
•Most important prognostic factors: lymph node involvement, tumour size, histological grade, receptor status
Stage
Description
Approximate 5-year survival
I
Localised, node-negative
95-99%
II
Small nodal involvement
75-85%
III
Locally advanced
40-70%
IV
Metastatic
20-30% (palliative intent)
•Triple-negative breast cancer - worst prognosis of molecular subtypes; more aggressive, higher recurrence within 5 years, limited targeted options

Investigations - Triple Assessment

All three components are required before any management decision. A score of 4 or 5 in ANY component mandates tissue biopsy.

Component
Tool
Score
Notes
Clinical
Examination
E1-E5
Lump characteristics, skin changes, axillary nodes
Imaging
Mammography (>40 yrs)
R1-R5
Detects microcalcifications, spiculate masses, architectural distortion
Imaging
Ultrasound (<40 yrs)
U1-U5
Preferred in younger/denser breasts; cystic vs solid
Histology
Core needle biopsy (gold standard)
B1-B5
ER/PR/HER2 status, grade - image-guided
Cytology
FNAC
B1-B5
Cytology only; used for cysts and lymph nodes
•Scoring: 1=normal, 2=benign, 3=uncertain/probably benign, 4=suspicious, 5=malignant
•Staging (node-positive/locally advanced): CT chest/abdomen/pelvis; bone scan or PET-CT for bone metastases
•MRI breast - used in lobular carcinoma, BRCA carriers, implant assessment, or pre-operative extent assessment
•Bloods: FBC, LFTs, bone profile (calcium, ALP) - baseline and screen for metastatic disease

Histological Types

•Invasive ductal carcinoma (NST) - ~75%; most common
•Invasive lobular carcinoma - ~10-15%; diffuse growth pattern; harder to detect on mammography
•DCIS - in situ (pre-invasive); basement membrane intact; non-obligate precursor to invasive ductal carcinoma

Prevention and Screening

•NHS Breast Screening Programme: three-yearly mammography for women aged 50-70 (extending to 47-73 in some areas)
•Chemoprevention in high-risk individuals (BRCA1/2, strong family history): tamoxifen or anastrozole (NICE TA612)
•Risk-reducing surgery for BRCA1/2 carriers: bilateral mastectomy and/or bilateral salpingo-oophorectomy (BSO) - BSO especially important in BRCA1 given concurrent ovarian cancer risk
•Protective: prolonged breastfeeding (each additional 12 months reduces invasive breast cancer risk by ~4.3%), regular physical activity, maintaining healthy weight