Inflammatory breast cancer

A clinicopathologic subtype of invasive breast cancer, featuring rapidly aggressive cancer along with diffuse erythema and oedema.

Epidemiology

• Rare - 1-5% of all breast cancers
• Often seen <1 year after negative screening mammogram

Pathophysiology

• No unique histologic subtype, molecular markers or genetic signature to account for inflammatory phenotype
• Mostly ductal, but can be lobular
• More likely to display aggressive features - high-grade nuclei, HER2 type or triple negative.
• Hallmark is diffuse involvement of dermal lymphatic channels within the breast and overlying skin, often without an underlying tumour mass. However, this can be missed due to sampling error and is not a pre-requisite for diagnosis.

Clinical presentation

• Clinical diagnosis
• Breast swelling/redness developing over a period of several weeks to 3 months
  • Neglected primary breast cancers that lead to secondary inflammatory changes within the breast shouldn't be classified as inflammatory breast cancer
• Breast heaviness, burning or tenderness, nipple inversion or retraction, peau d'orange, or skin discolouration
  • Results from blockage of lymphatics
• Some will have a discrete palpable mass
• Some will have palpable axillary/supraclavicular nodes
• Commonly initially diagnosed as infection
  • Would not have fever, leucocytosis, or marked breast pain
  • Won't resolve with antibiotics

Diagnostic criteria

• Rapid onset (6 months) of breast oedema or peau d'orange
• Erythema involving at least one third of the breast
• Biopsy consistent with invasive carcinoma

Imaging

• Mammogram +/- tomosynthesis
  • Skin thickening
  • Unilaterally diffusely increased breast density
  • Discrete mass
  • Architectural distortion
  • Suspicious calcifications
  • Enlarged axillary nodes
• USS including axilla +/- biopsy
• If other imaging unhelpful, consider MRI
  • Note that MRI of ipsilateral breast won't change management if diagnosis already confirmed

Staging

• 20-35% have distal mets, and axillary nodal metastases are very common
• Standard staging would CT CAP or PET
• Brain MRI in selected patients - if symptoms suggest brain mets
• Inflammatory cancer is stage T4d
  • If no mets, stage IIIB or IIIC
  • If mets, stage IV

Treatment

• Stage III
  • Systemic (CTX +/- HER2)
    • Most patients will have at least a partial response
  • Consider RTX if no response to CTX
    • If no response to CTX and RTX, consider palliation - will be hard to offer surgery if skin is still no good
  • Modified radical mastectomy + ALND
    • Generally 3-5 weeks after completion of CTX, when neutropaenia has resolved and patient is recovered
    • Lumpectomy is not considered - very high rates of local recurrence
    • All patients require clearance of level I and II, with removal of any palpable nodes in level III. No role for SLNB.
    • No immediate breast reconstruction - might delay RTX
  • Radiotherapy
    • 4-6 weeks after surgery, when able to raise arm above head
    • Ipsilateral chest wall, axillary and supraclavicular nodes, and internal mammary chain
  • Prolonged endocrine therapy/HER2 therapy if applicable
    • ER therapy during/immediately after RTX
• Stage IV
  • Systemic therapy
  • Surgery or RTX if indicated for palliation
    • Does not improve overall survival
    • For example, if primary tumour is enlarging but distant mets are well-controlled, or with triple negative cancers who have a good response to initial chemotherapy to prevent rapid growth of primary tumour during planned breaks in CTX

Prognosis

• 2 year breast cancer specific survival of 76%
• 5 year survivals
  • Stage III 40%
  • Stage IV 11%
• 15 year survival about 20%
• Response to initial chemotherapy is most important indicator

Surveillance

• Examination and review of symptoms every 3-6 months