What is the treatment for anaplastic large cell lymphoma (ALCL) of the breast?

Treatment of Anaplastic Large Cell Lymphoma of Breast

The treatment of breast-associated anaplastic large cell lymphoma (ALCL) should include complete surgical excision with implant removal for localized disease, while systemic therapy with brentuximab vedotin plus CHP (cyclophosphamide, doxorubicin, prednisone) is recommended for invasive or advanced disease. 1

Classification and Diagnosis

Breast-associated ALCL typically presents in two main forms:

• Breast implant-associated ALCL (BIA-ALCL): A distinct entity from systemic ALCL
• Primary cutaneous ALCL (pcALCL) affecting the breast
• Secondary breast involvement from systemic ALCL

Proper diagnosis requires:

• Excisional or incisional biopsy
• Immunophenotyping (CD30+, typically ALK-)
• Staging workup including PET/CT scan and bone marrow biopsy

Treatment Algorithm

1. Localized Disease (Confined to Capsule/Breast)

• First-line: Complete surgical excision with removal of implant and total capsulectomy 2, 1
• Adjuvant therapy: Consider localized radiation therapy (24-30 Gy) for positive margins 2

2. Regional Disease (Lymph Node Involvement)

• First-line: Complete surgical excision plus regional lymph node dissection
• Adjuvant therapy: Consider systemic therapy and/or radiation therapy

3. Advanced/Systemic Disease

• First-line systemic therapy: Brentuximab vedotin plus CHP (cyclophosphamide, doxorubicin, prednisone) 2, 3

  • This regimen is FDA-approved for previously untreated systemic ALCL or other CD30-expressing peripheral T-cell lymphomas 3
  • Superior to CHOP alone based on the ECHELON-2 trial 1

• Alternative regimens if brentuximab vedotin is unavailable:

  • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
  • CHOEP (CHOP plus etoposide)
  • Dose-adjusted EPOCH

4. Relapsed/Refractory Disease

• Preferred therapy: Brentuximab vedotin (if not used in first-line) 2

• Salvage regimens (if brentuximab vedotin was used in first-line):

  • DHAP (dexamethasone, cisplatin, cytarabine)
  • ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin)
  • GDP (gemcitabine, dexamethasone, cisplatin)
  • GemOx (gemcitabine, oxaliplatin)
  • ICE (ifosfamide, carboplatin, etoposide) 2

• Consolidation therapy: Consider high-dose therapy with autologous stem cell transplantation for chemosensitive disease 2

Prognostic Factors

Several factors affect prognosis and may guide treatment intensity:

• ALK status: ALK-positive ALCL has better prognosis (5-year OS 70-80%) than ALK-negative (5-year OS 49%) 1
• DUSP22 rearrangement: In ALK-negative cases, confers better prognosis 1
• Disease stage: Stage I-II has more favorable outcomes
• Age: Patients ≥60 years have worse outcomes
• Performance status: ECOG >2 indicates poorer prognosis

Follow-up and Monitoring

For patients achieving complete response:

• Physical examination every 3-6 months for 2 years, then as clinically indicated
• Surveillance imaging no more often than every 6 months for 2 years, then annually for 5 years 1

Important Considerations

• BIA-ALCL has a generally favorable prognosis when treated with complete surgical excision for localized disease
• Systemic therapy is essential for invasive or advanced disease
• PET/CT is preferred over CT alone for accurate response assessment 1
• Clinical trials should be considered when available, especially for relapsed/refractory disease 2

The management of breast-associated ALCL has evolved significantly with the development of targeted therapies like brentuximab vedotin, which has shown substantial activity in both systemic and primary cutaneous ALCL due to the high CD30 expression characteristic of this disease 4.