What is the primary treatment for triple negative breast cancer?

Treatment of Triple Negative Breast Cancer

Cytotoxic chemotherapy is the primary treatment for triple-negative breast cancer (TNBC), with taxane-based regimens being the standard of care for first-line therapy in patients who have progressed after adjuvant anthracycline-based chemotherapy. 1

First-Line Treatment Approach

• For early-stage TNBC, neoadjuvant chemotherapy is preferred for stage II or III disease before definitive surgery 2
• Dose-dense anthracycline and taxane-based regimens are preferred for neoadjuvant treatment of stage II-III TNBC 2
• For metastatic TNBC, single-agent chemotherapy is recommended over combination chemotherapy as first-line treatment for most patients 1
• Combination chemotherapy should be reserved for patients with life-threatening disease or those requiring rapid symptom control 1
• Patients with triple-negative, PD-L1-positive metastatic breast cancer may be offered immune checkpoint inhibitors in addition to chemotherapy as first-line therapy 1

Chemotherapy Regimens

• Available chemotherapy agents/regimens for TNBC include: 1

  • Anthracycline-containing regimens (doxorubicin, epirubicin)
  • Taxane-based regimens (paclitaxel, docetaxel)
  • Platinum-based combinations
  • Capecitabine
  • Vinorelbine
  • Eribulin

• Taxane-based regimens have level 1 evidence as first-line therapy for patients progressing after adjuvant anthracycline-based chemotherapy 1

Sequential vs. Combination Therapy

• For most patients with metastatic TNBC without life-threatening disease, sequential use of single cytotoxic drugs provides equivalent overall survival compared to combination chemotherapy, with less toxicity and better quality of life 1
• In TNBC with frequent visceral involvement, aggressive course, and risk of rapid deterioration, combination chemotherapy is often required 1
• However, triple-negative biology alone does not always necessitate combination chemotherapy, as patients without extensive or life-threatening disease can be treated successfully with single-agent chemotherapy 1

Special Considerations

• For patients with triple-negative MBC with germline BRCA mutations previously treated with chemotherapy, poly (ADP-ribose) polymerase (PARP) inhibitors may be offered instead of chemotherapy 1
• Patients with triple-negative MBC who have received at least two prior therapies should be offered treatment with sacituzumab govitecan 1
• For early-stage TNBC with tumors <5 mm, surgical excision alone may be appropriate, though many experts recommend adjuvant chemotherapy even for these small tumors 2

Surgical Management

• Sentinel lymph node biopsy is standard for clinically node-negative patients 2
• For patients with clinically positive nodes who receive neoadjuvant chemotherapy, sentinel lymph node biopsy may be considered if nodes become clinically negative after treatment 2
• For residual nodal disease after neoadjuvant therapy, axillary lymph node dissection is recommended, especially for macrometastases >2mm 2

Radiation Therapy

• Post-mastectomy radiation therapy should be considered for patients with positive lymph nodes 2
• Post-mastectomy radiation therapy should be considered for patients with positive or close margins 2

Treatment Algorithm for TNBC

1. Early-stage TNBC (Stage I-III):

   • For stage II-III: Neoadjuvant chemotherapy (anthracycline + taxane) followed by surgery 2
   • For stage I with tumor >5mm: Consider adjuvant chemotherapy 2
   • For tumors <5mm: Surgical excision with consideration of adjuvant chemotherapy 2

2. Metastatic TNBC:

   • First-line: Single-agent taxane-based chemotherapy (if progressed after adjuvant anthracycline) 1
   • For PD-L1 positive disease: Consider adding immune checkpoint inhibitor to chemotherapy 1
   • For life-threatening disease: Consider combination chemotherapy 1
   • For germline BRCA mutations: Consider PARP inhibitors after prior chemotherapy 1
   • After ≥2 prior therapies: Sacituzumab govitecan 1

Limitations and Future Directions

• There is no standard approach for patients requiring second- or further-line treatment for metastatic TNBC, as few data support the superiority of any particular regimen 1
• Duration of each regimen and number of regimens should be tailored to each individual patient 1
• Continuing beyond third-line treatment may be justified in patients with good performance status and response to previous chemotherapy 1
• High-dose chemotherapy should not be used 1
• Emerging approaches include targeted therapies, immunotherapy, and nanoparticle-based therapies 3, 4

TNBC presents with different clinical features from other breast cancer subtypes, and treatment strategies must be selected according to these specific characteristics to optimize outcomes 5.