What is inflammatory carcinoma of the breast?

Inflammatory Breast Cancer (IBC)

Inflammatory breast cancer is the most aggressive form of breast cancer characterized by rapid onset of breast erythema, edema, and/or peau d'orange, often without an underlying palpable mass, with pathological confirmation of invasive carcinoma. 1

Definition and Clinical Presentation

Inflammatory breast cancer represents the most aggressive presentation of breast cancer, accounting for approximately 1-5% of all breast cancer cases in the United States. 1 It is characterized by:

• Rapid onset of symptoms (typically within 6 months)
• Diffuse erythema and edema of the breast
• Peau d'orange appearance (skin resembling orange peel)
• Warm breast
• With or without an underlying palpable mass 1

The disease is defined primarily by its clinical presentation, with the American Joint Committee on Cancer (AJCC) describing it as "a clinicopathological entity characterized by diffuse erythema and edema of the breast, often without an underlying palpable mass." 1

Diagnostic Criteria

The international expert panel consensus states that minimum criteria for IBC diagnosis include:

• History of rapid onset of breast erythema, edema and/or peau d'orange, and/or warm breast
• Duration of history no more than 6 months
• Erythema occupying at least one-third of the breast
• Pathological confirmation of invasive carcinoma 1

While dermal lymphovascular tumor emboli seen on skin punch biopsy is pathognomonic, it is not required for diagnosis. 1

Pathology and Biology

IBC is characterized by:

• Aggressive biological behavior
• Rapid proliferation
• Early local and distant metastases
• Younger age of onset compared to other breast cancers
• Lower overall survival rate 2

Historically, IBC had less than a 5% survival rate beyond 5 years when treated with surgery or radiation therapy alone. 2

Common Diagnostic Pitfalls

IBC is frequently misdiagnosed as:

• Mastitis
• Generalized dermatitis 2

This misdiagnosis leads to delayed treatment and worse outcomes. The nonspecific diagnostic criteria and clinical similarity to inflammatory conditions are primary causes of delayed diagnosis. 1

Management Approach

The American College of Oncology recommends a multimodality treatment approach for IBC following a specific sequence: 3

1. Primary (Neoadjuvant) Systemic Chemotherapy

   • Anthracycline and taxane-based regimens as first-line treatment
   • Addition of trastuzumab for HER2-positive disease 3, 4

2. Surgery

   • Modified radical mastectomy is standard
   • Skin-sparing mastectomy is contraindicated
   • Breast-conserving approaches should only be considered within clinical trials
   • Axillary dissection is preferred over sentinel lymph node biopsy 3

3. Radiation Therapy

   • Mandatory component following mastectomy
   • Targets chest wall, supraclavicular region, infraclavicular region, internal mammary lymph nodes, and axillary bed at risk
   • Total dose escalation to 66 Gy for high-risk patients (age <45 years, close/positive margins, ≥4 positive lymph nodes after preoperative chemotherapy, poor response to preoperative treatment)
   • Skin dose should be modulated to ensure moderate acute erythema 3, 5

Recurrence Patterns and Follow-up

IBC has unique recurrence patterns:

• Common sites of first recurrence include bone (28%), central nervous system, lung, and liver (all 21%)
• HER2-positive and triple-negative subtypes have higher rates of CNS recurrence 6

Follow-up recommendations:

• Regular imaging during and after treatment to assess response
• Physical examinations every 3-6 months after completing treatment
• Yearly mammogram of the contralateral breast
• Consider yearly ultrasound of locoregional lymph nodes 3

Prognosis

Despite improvements in treatment, IBC remains a disease with poor prognosis:

• Median survival for stage III: 66 months
• Median survival for stage IV: 26 months
• For stage III patients receiving multimodality therapy, median survival improves to 107 months 6

The combined-modality approach has transformed IBC from a disease with local control rates less than 50% to one with local control rates of 70-80%. In patients whose disease responds to chemotherapy, the 5-year local control rates are even higher. 5

Future Directions

Research into molecular determinants of IBC has provided several promising therapeutic targets:

• Angiogenic modulators
• Farnesyl transferase inhibitors
• p53 modulators 4

These targeted therapies may improve the overall prognosis for women with IBC in the future.