Inflammatory Breast Cancer: Epidemiology, Causes, Pathogenesis, Pathology, Symptoms, Diagnosis, Treatment, Prognosis and Prevention

Inflammatory Breast Cancer (IBC)

~Introduction

Inflammatory Breast Cancer (IBC) is a rare but very aggressive form of breast cancer that progresses rapidly and has a poorer prognosis compared to other types of breast cancer. Unlike typical breast cancer, IBC does not usually present as a distinct lump. Instead, it causes inflammation-like changes in the breast, such as redness, swelling, warmth, and skin thickening. Because these symptoms resemble infection or mastitis, diagnosis is often delayed.

Inflammatory breast cancer accounts for 1–5% of all breast cancers, but it is responsible for a disproportionately high number of breast cancer–related deaths due to its aggressive nature and early spread to lymph nodes and distant organs. Early recognition and prompt treatment are critical for improving survival.

~Definition

Inflammatory Breast Cancer is defined as a clinically aggressive carcinoma of the breast characterized by rapid onset of erythema, edema, and peau d’orange appearance of the skin, caused by tumor emboli blocking the dermal lymphatic vessels, with or without a palpable mass.

~Epidemiology

• Accounts for 1–5% of breast cancers

• More common in younger women compared to other breast cancers

• Higher incidence in African and African-American women

• Can occur in men, though extremely rare

• Usually diagnosed at an advanced stage (Stage III or IV)

~Etiology and Risk Factors

The exact cause of inflammatory breast cancer is unknown, but several risk factors are associated with its development.

Risk Factors

• Female gender

• Younger age at diagnosis

• Obesity

• Genetic mutations (e.g., BRCA mutations)

• Family history of breast cancer

• Hormonal factors

Unlike infection, IBC is not caused by bacteria and does not respond to antibiotics.

~Pathogenesis

The hallmark of inflammatory breast cancer is tumor cell invasion of the dermal lymphatic channels.

Mechanism

1. Malignant breast epithelial cells form tumor emboli

2. These emboli block lymphatic drainage in the skin

3. Lymphatic obstruction leads to:

   • Redness (erythema)

   • Swelling (edema)

   • Thickened skin (peau d’orange)

4. Rapid tumor growth and early metastasis occur

~Pathology

Gross Pathology

• Breast appears enlarged, heavy, and warm

• Diffuse redness involving more than one-third of the breast

• Skin thickening and induration

• Nipple may be flattened or retracted

• No well-defined mass in many cases

Microscopic Pathology

• Invasive ductal carcinoma is most common

• Tumor emboli present in dermal lymphatic vessels

• High-grade tumor cells

• Frequent lymphovascular invasion

Molecular Features

• Often HER2-positive

• Frequently triple-negative in some populations

• High proliferation index (Ki-67)

~Clinical Features

Key Clinical Criteria

For diagnosis, symptoms usually:

• Develop rapidly (within weeks to months)

• Involve at least one-third of the breast

Symptoms

• Rapid breast enlargement

• Redness and warmth of breast skin

• Pain or tenderness

• Itching or burning sensation

• Peau d’orange appearance

• Nipple inversion or flattening

Signs

• Edematous, thickened skin

• Enlarged axillary or supraclavicular lymph nodes

• Absence of a discrete lump in many cases

~Differential Diagnosis

IBC must be differentiated from:

• Acute mastitis

• Breast abscess

• Cellulitis

• Locally advanced breast cancer

• Paget’s disease of the breast

Lack of response to antibiotics strongly suggests IBC.

~Diagnosis

Diagnosis of inflammatory breast cancer is primarily clinical, supported by imaging and biopsy.

Clinical Diagnosis

Based on:

• Rapid onset of symptoms

• Typical inflammatory signs

• Extensive skin involvement

Imaging Studies

1. Mammography

• Diffuse skin thickening

• Increased breast density

• May not show a distinct mass

2. Ultrasound

• Skin and tissue edema

• Underlying mass or lymphadenopathy

3. MRI

• Most sensitive imaging modality

• Shows extent of disease

• Useful for treatment planning

4. PET-CT

• Detects distant metastases

Biopsy

• Core needle biopsy of breast tissue

• Skin punch biopsy to detect dermal lymphatic invasion

• Confirms invasive carcinoma

~Staging

Inflammatory breast cancer is automatically classified as Stage III (T4d), regardless of tumor size.

• Stage III: No distant metastasis

• Stage IV: Distant metastasis present

~Treatment

Management of inflammatory breast cancer requires a multimodal approach.

1. Neoadjuvant Chemotherapy

• First line of treatment

• Shrinks tumor and controls microscopic disease

• Common regimens include:

  • Anthracyclines

  • Taxanes

• HER2-positive tumors receive targeted therapy (Trastuzumab)

2. Surgery

• Performed after chemotherapy

• Modified radical mastectomy is standard

• Breast-conserving surgery is not recommended

• Includes axillary lymph node dissection

3. Radiotherapy

• Given after surgery

• Reduces local recurrence

• Targets chest wall and lymph nodes

4. Hormonal Therapy

• For hormone receptor–positive tumors

• Tamoxifen or aromatase inhibitors

5. Targeted Therapy

• HER2-positive tumors treated with:

  • Trastuzumab

  • Pertuzumab

~Prognosis

Inflammatory breast cancer has a poorer prognosis compared to other breast cancers.

Survival Rates

• 5-year survival: 40–50%

• Prognosis improves with early and aggressive treatment

Poor Prognostic Factors

• Distant metastasis

• Triple-negative subtype

• Poor response to chemotherapy

• Extensive lymph node involvement

~Complications

• Early metastasis (lungs, liver, bone, brain)

• Local recurrence

• Lymphedema

• Treatment-related toxicity

• Psychological distress

~Prevention and Early Detection

• Awareness of rapid breast changes

• Prompt evaluation of non-resolving breast inflammation

• Early biopsy if symptoms persist beyond 2–3 weeks

• Regular breast screening

~Difference Between IBC and Mastitis

Feature	Inflammatory Breast Cancer	Mastitis
Cause	Cancer	Infection
Response to antibiotics	No	Yes
Skin changes	Persistent	Temporary
Palpable lump	Usually absent	May be present
Progression	Rapid	Improves with treatment

~Conclusion

Inflammatory breast cancer is a highly aggressive and life-threatening form of breast cancer that presents with inflammatory skin changes rather than a typical breast lump. Because it mimics infection, early diagnosis is often missed, leading to advanced-stage presentation. Prompt recognition, early biopsy, and a multidisciplinary treatment approach are essential for improving survival.

Advances in chemotherapy, targeted therapy, surgery, and radiotherapy have improved outcomes, but prognosis remains guarded. Increased awareness among healthcare professionals and patients is crucial for early detection and timely management.