What is the management of triple negative breast cancer?

Management of Triple Negative Breast Cancer

The management of triple negative breast cancer (TNBC) requires a structured approach with chemotherapy as the mainstay of treatment, with the addition of immune checkpoint inhibitors for PD-L1 positive disease, and consideration of PARP inhibitors for patients with germline BRCA mutations. 1

Diagnosis and Initial Assessment

• At diagnosis, a biopsy should be performed to confirm histology and assess tumor biology (ER, PgR, HER2) 1
• For TNBC, additional biomarkers should be assessed:
  • PD-L1 status
  • Germline BRCA1/2 mutation status 1
• Minimum imaging for staging includes:
  • CT of chest and abdomen
  • Bone scintigraphy 1
  • 18F-FDG PET-CT may be used as an alternative 1

Treatment Algorithm for Early-Stage TNBC

Surgical Management

• Wide excision with clear margins or mastectomy depending on tumor size and location
• Axillary staging is required
• Post-mastectomy radiation therapy is recommended for patients with T3-T4 tumors and/or ≥4 positive lymph nodes 1

Neoadjuvant/Adjuvant Systemic Therapy

1. Neoadjuvant chemotherapy is preferred for most patients with TNBC to:

   • Assess pathologic response
   • Guide adjuvant therapy decisions 2
   • Standard regimen: Anthracycline and taxane-based chemotherapy 3, 2
   • Consider addition of carboplatin (improves pCR rates but increases toxicity) 3, 2

2. For patients with residual disease after neoadjuvant chemotherapy:

   • Adjuvant capecitabine is recommended (significantly improves outcomes) 2

Treatment Algorithm for Metastatic TNBC

First-line Treatment

1. For PD-L1 positive TNBC:

   • Immune checkpoint inhibitor plus chemotherapy (atezolizumab plus nab-paclitaxel or pembrolizumab plus chemotherapy) 1

2. For PD-L1 negative TNBC:

   • Single-agent chemotherapy is preferred
   • Combination chemotherapy may be considered for symptomatic or immediately life-threatening disease 1
   • Options include platinum-based or non-platinum-based regimens based on individual assessment 1

Second-line and Beyond

1. For patients with germline BRCA1/2 mutations:

   • Oral PARP inhibitor (olaparib or talazoparib) is recommended over chemotherapy in the first through third-line setting 1

2. For patients who have received at least two prior therapies:

   • Sacituzumab govitecan is recommended 1

3. Other chemotherapy options (sequential single agents preferred unless rapid response needed):

   • Anthracycline-based regimens (if not used previously)
   • Taxane-based regimens
   • Capecitabine
   • Eribulin
   • Vinorelbine
   • Platinum agents (cisplatin, carboplatin) 1

Special Considerations

Monitoring Response

• Regular clinical assessment and imaging to evaluate treatment response
• Re-biopsy may be appropriate in cases of mixed response 1

Treatment Challenges

• TNBC has higher risk of early recurrence and metastasis compared to other breast cancer subtypes 4, 5
• Median time to relapse and death is shorter than other subtypes 6
• Inflammation may play a role in early recurrence; research suggests elevated IL-6 levels after doxorubicin exposure 4

Emerging Approaches

• Novel targeted therapies being evaluated:
  • PI3K-AKT-mTOR pathway inhibitors
  • Tumor microenvironment targeted therapies 3
• Molecular subtyping of TNBC may guide future treatment selection 2

Pitfalls to Avoid

• Delaying treatment initiation due to TNBC's aggressive nature
• Underestimating the importance of PD-L1 and BRCA testing which directly impact treatment decisions
• Overlooking the benefit of adjuvant capecitabine in patients with residual disease after neoadjuvant therapy
• Continuing ineffective treatments without considering clinical trial options for refractory disease

The management of TNBC requires prompt diagnosis, comprehensive biomarker assessment, and aggressive multimodal therapy to improve survival outcomes in this aggressive breast cancer subtype.