35. Benign breast neoplasms and precancerous conditions

1. Definition

• Benign breast disease → non-malignant lesions of the breast: aberrations of normal development, benign tumours, inflammation
• Precancerous conditions → lesions that mark or carry an increased risk of invasive breast cancer
• Triple assessment → clinical examination + imaging + needle biopsy; applied to every breast lump; accuracy about 99.6%

2. Aetiology and risk factors

• Oestrogen and progesterone → cyclical changes, fibroadenoma growth, cysts
• Age → each lesion has a typical age
• Hormone replacement therapy (HRT) → new cysts after the menopause
• Family history, genetic mutations → precancerous lesions

3. Pathogenesis

• Aberrations of normal development and involution (ANDI):
  1. Development (15–25 years) → fibroadenoma, juvenile hypertrophy
  2. Cyclical change (25–40 years) → cyclical mastalgia, nodularity (fibrocystic change)
  3. Involution (35–55 years) → cysts, duct ectasia, sclerosing adenosis
• Precancer → epithelial proliferation → atypia → carcinoma in situ → invasive cancer (not every lesion progresses)

4. Classification

Benign breast lesions

• Fibroadenoma
• Breast cyst
• Fibrocystic change
• Intraductal papilloma
• Phyllodes tumour → benign, borderline or malignant
• Hamartoma (fibroadenolipoma), adenoma, lipoma
• Fat necrosis, galactocele

Cancer risk of benign lesions

1. Non-proliferative (cysts, simple fibroadenoma, duct ectasia) → little or no increased risk (relative risk about 1.3)
2. Proliferative without atypia (usual ductal hyperplasia, sclerosing adenosis, papilloma, radial scar) → relative risk 1.3–1.9; radial scar 1.8–3.0, excise
3. Proliferative with atypia (atypical ductal or lobular hyperplasia) → relative risk 4–5
4. Lobular carcinoma in situ (LCIS) → relative risk about 7
5. Ductal carcinoma in situ (DCIS) → non-invasive cancer; direct precursor

5. Benign neoplasms

A. Fibroadenoma

• Most common tumour under 30 years; about 10% of women
• Stromal and epithelial elements, encapsulated
• Firm, smooth or lobulated, painless, highly mobile ("breast mouse")
• Ultrasound → well defined, oval, hypoechoic
• Natural history → 50% resolve, 25% stay the same, 25% grow
• Complex fibroadenoma → relative risk about 3
• Malignant change → rare, about 0.2%
• Treatment:
  • Core biopsy if over 25 years
  • Confirmed on core biopsy, < 3 cm → reassure, no excision needed
  • Excision → > 3 cm, rapid growth, suspected phyllodes, patient preference
  • Enlarging fibroadenoma → phyllodes found in about 2.4%
  • Giant (> 5 cm) and juvenile fibroadenoma → excision

B. Breast cyst

• Women over 35 years to menopause; at least 1 in 14 women
• Smooth, well-defined, may be tender; multiple or recurrent in 50%
• Ultrasound → anechoic with posterior enhancement
• Simple cyst → aspirate if symptomatic; cytology only if blood-stained
• Core biopsy or excision → blood-stained fluid, residual mass, irregular wall, refilling within 2 weeks, complex cyst, new cyst after the menopause
• Intracystic carcinoma → about 0.1%

C. Intraductal papilloma

• Polyp of a large subareolar duct
• Most common cause of bloody nipple discharge → papilloma in 60–80% of single-duct bloody discharge
• Within 5 cm of the nipple; palpable in about 30%
• Unilateral single-duct discharge → malignancy in up to 20%
• Diagnosis → ultrasound, mammography, ductography or ductoscopy, core biopsy
• Treatment → microdochectomy (excision of the duct)
• Atypia → upgrade to cancer in about 50%; excise
• Multiple papillomas (papillomatosis) → increased cancer risk

D. Phyllodes tumour

• Fibroepithelial tumour with cellular stroma, leaf-like pattern
• Age 35–50 years, about 10 years older than fibroadenoma
• Malignant → under 5%
• Large, rapidly growing, smooth mass; may stretch the skin
• Core biopsy may not separate it from fibroadenoma
• Treatment → wide local excision; benign → clear margin; borderline or malignant → 5–10 mm or more; mastectomy for large tumours
• No axillary surgery → spread is haematogenous
• Local recurrence if margins are inadequate

E. Other benign lesions

• Hamartoma → "breast within a breast"; looks like fibroadenoma
• Lipoma
• Fat necrosis → after trauma, surgery or radiotherapy; hard mass, skin tethering, calcifications; mimics cancer
• Galactocele → milk retention cyst after lactation; aspiration diagnostic and curative

6. Precancerous conditions

A. Atypical ductal hyperplasia (ADH)

• Found on core biopsy for calcifications
• Upgrade to DCIS or cancer at excision in 10–20% → surgical excision
• Risk reduction → tamoxifen or aromatase inhibitor, screening

B. Atypical lobular hyperplasia (ALH) and LCIS

• Lobular neoplasia → incidental finding, no mass, no calcifications
• LCIS → marker of risk in both breasts, not a direct precursor
• Classic LCIS → observation, screening, chemoprevention (tamoxifen → 59% fewer cancers in a trial)
• Pleomorphic or florid LCIS → excision to clear margins

C. Ductal carcinoma in situ (DCIS)

• Malignant cells within the ducts, basement membrane intact
• Usually found as microcalcifications on screening mammography
• Direct precursor of invasive ductal carcinoma → 10–50% become invasive if untreated
• Treatment → breast-conserving surgery + radiotherapy, or mastectomy; no axillary clearance; sentinel node biopsy only with mastectomy
• Endocrine therapy → oestrogen receptor-positive DCIS

D. High-risk states

• BRCA1, BRCA2 mutations → lifetime risk up to 70%
• Previous chest radiotherapy (Hodgkin's lymphoma)
• Strong family history
• Management → MRI screening, chemoprevention, risk-reducing mastectomy

7. Clinical picture

Symptoms

• Breast lump
• Nipple discharge → single duct, bloody
• Mastalgia → cyclical or non-cyclical
• No symptoms → found on screening (calcifications, LCIS, DCIS)

Signs

• Mobile, smooth, rubbery lump → fibroadenoma
• Fluctuant, smooth lump → cyst
• Large, bosselated lump, stretched shiny skin → phyllodes tumour
• Discharge from one duct on pressure at one point of the areola → papilloma

8. Diagnosis

Imaging

• Ultrasound → first-line under 40 years; solid versus cystic
• Mammography → over 40 years; calcifications
• MRI → high-risk women, dense breasts, implants
• Scoring → BI-RADS (Breast Imaging Reporting and Data System)

Pathology

• Core needle biopsy → preferred over fine-needle aspiration
• Vacuum-assisted biopsy → small lesions, calcifications, removal of benign lesions
• Excision biopsy → discordant triple assessment

9. Differential diagnosis

• Breast carcinoma
• Inflammatory lesions → abscess, granulomatous mastitis
• Fat necrosis
• Lipoma, sebaceous cyst

10. Complications

• Phyllodes tumour → local recurrence, malignant change
• Missed carcinoma → discordant triple assessment not followed up
• Excision → haematoma, infection, cosmetic deformity