50th Webinar on Triple Negative Breast Cancer

Introduction

• Focus: Oncology and pathology related to triple negative breast cancer (TNBC).
• Translation: Available in Spanish by Ricardo Pardo.
• Speakers: From the USA, Jordan, and Sweden.
• Panelists: Andreas, Peter Barry, and others.

Talk by Prof. Mohammed Bazuki on Pathology of Triple Negative Breast Cancer

Definition

• TNBC: Breast cancer negative for ER, PR, and HER2 receptors.
• Normal breast: Composed of luminal and basal layers. TNBC may arise from these layers.

Classification

• Molecular Subtypes:

  • Basal-like: High-grade, often associated with BRCA mutations.
  • Other types: Normal breast-like, Claudin-low, molecular apocrine.

• Morphologic Level:

  • High-grade: Invasive carcinoma, metaplastic carcinoma, apocrine carcinoma, no special type.
  • Low-grade: Adenoid cystic carcinoma, secretory carcinoma, low-grade metaplastic carcinomas.

Pathologic Features

• Basal-like Breast Cancer:

  • Expresses basal markers (e.g., cytokeratin 5/6, EGFR).
  • Poor prognosis, aggressive course.
  • High KI67, necrosis, lymphocytic infiltration.

• Immunoprofile:

  • Negative for ER, PR, HER2.
  • Positive for cytokeratin 5/6, EGFR, P63, CK14, TRP S1, GATA3, CK17.

Other TNBC Types

• Metaplastic Carcinomas:

  • Low-grade vs. high-grade (spindle cell, squamous cell, etc.).

• Secretory Carcinoma:

  • Very rare, characterized by ETV6-NTRK3 gene fusion.

• Adenoid Cystic Carcinoma:

  • Low aggressive potential, MEC-NFIB translocation.

Residual Cancer Burden (RCB)

• Assessment:
  • Parameters: Tumor dimensions, percentage of tumor cells, lymph node involvement.
  • Tools: MD Anderson equation for RCB scoring.

Tumor-Infiltrating Lymphocytes (TILs)

• Evaluated for stromal components.
• Correlates with pathologic response to neoadjuvant therapy.

PD-L1 and BRCA Mutations

• Increased PD-L1 expression in TNBC.
• BRCA1 mutations: Common in Basal-like subtypes.

Talk by Oncologist from Jordan on Neoadjuvant and Adjuvant Therapy

Importance of Neoadjuvant Therapy

• Benefits:
  • Improved event-free and overall survival for patients achieving complete pathologic response (pCR).
  • Allows assessment of treatment response before surgery.

Enhancing pCR

• Dose-Dense Chemotherapy:

  • More effective with regimens like weekly paclitaxel or carboplatin.

• Platinum Addition:

  • Increases pCR by 15-20%, especially in patients under 50.

• Checkpoint Inhibitors:

  • Pembrolizumab and atezolizumab: Increase pCR and event-free survival.

Post-Neoadjuvant Strategies

• Capecitabine: Improves survival for residual disease after chemotherapy.
• Olaparib: 1-year treatment for BRCA-mutation carriers improves overall survival.

Clinical Trials and Future Outlook

• Enrollment in trials recommended for TNBC patients.
• Personalized treatment strategies, emphasizing the role of checkpoint inhibitors and targeted therapies.

Talk by Antonio from Sweden on Metastatic Triple Negative Breast Cancer

Current Statistics

• Median survival: 10 months (Sweden), 14 months (France).

First-Line Treatments

• PD-L1 Positive:

  • Pembrolizumab or atezolizumab with chemotherapy.

• Germline BRCA Mutation:

  • PARP inhibitors like olaparib or talazoparib.

Chemotherapy

• Combination therapies preferred for platinum-based regimens (e.g., carboplatin).
• Single-agent options: Anthracyclines, taxanes.

Future Directions

• Improving biomarkers for treatment efficacy (beyond PD-L1).
• Recognizing HER2-low breast cancer for targeted therapies.
• Antibody-drug conjugates like Trastuzumab deruxtecan and sacituzumab govitecan showing promise.

Q&A and Discussion

Neoadjuvant Therapy Considerations

• Varied opinions on T1, node-negative tumors.
• Emphasis on integrated care between surgeons, oncologists, pathologists, and radiologists.

Metastatic TNBC Management

• Balance between survival benefits and quality of life in treatment decisions.
• Continuous research for better treatment algorithms and real-world evidence.

Special Scenarios

• Pregnancy: Chemotherapy based on trimester, surgery approach adjusted accordingly.
• Positive BRCA Mutation: Risk-reduction strategies and individualized surgical decisions.

Pathology Insights

• Treatment impact on histologic features (e.g., fibrosis, necrosis, TILs).
• Molecular subtyping and PD-L1 evaluation critical in defining treatment paths.

Summary

• Comprehensive care involving multidisciplinary approaches is crucial for managing TNBC.
• Ongoing trials and research to refine strategies and improve patient outcomes.

Conclusion

• Webinar successfully discussed latest advancements in TNBC pathology and treatment.
• Highlighted the importance of collaboration and personalized treatment in improving patient care.