Locally_Advanced_Breast_Cancer_2025.pptx

Locally Advanced Breast Cancer (LABC)

1. Locally Advanced Breast Cancer (LABC) Current Management & Evolving Landscape 2025 Update For Oncology Specialists

2. Definition & Classification • AJCC 8th edition: Stage III (T3–T4 and/or N2–N3) • Includes large primary tumors, skin/chest wall involvement, or fixed/matted axillary nodes • Excludes distant metastases (M0)

3. Epidemiology & Clinical Significance • 10–30% of breast cancers present as LABC globally • Higher prevalence in low- and middle-income countries • Major cause of breast cancer–related mortality • Represents an opportunity for cure with multimodal therapy

4. Diagnostic Workup • Imaging: Mammography, Ultrasound, MRI, PET-CT for staging • Biopsy: Core needle biopsy with ER, PR, HER2, Ki-67 testing • Multigene assays and genomic profiling for selected cases • Staging: Chest, abdomen, bone imaging if symptomatic

5. Molecular Subtypes & Therapeutic Implications • Luminal A/B: Endocrine + chemo (if high-risk) • HER2+: Anti-HER2 therapy (trastuzumab, pertuzumab) • TNBC: Chemotherapy ± immunotherapy • Molecular subtype predicts response to neoadjuvant therapy

6. Neoadjuvant Therapy • Standard: Anthracycline + taxane-based regimens • HER2+: Dual blockade (trastuzumab + pertuzumab) • TNBC: Addition of pembrolizumab (KEYNOTE-522) • Goal: Downstage tumor, assess pCR as a prognostic marker

7. Surgical Management • Type: Modified radical mastectomy or breast-conserving surgery if feasible • Axillary management: Sentinel vs. axillary dissection post-NAC • Reconstruction: Immediate or delayed, depending on response and radiation plans

8. Adjuvant Therapy • Radiotherapy: Chest wall and regional nodes • Endocrine therapy: For ER/PR+ disease • HER2+: Continue trastuzumab to complete 1 year ± T-DM1 for residual disease • Escalation/de-escalation based on pathologic response

9. Emerging Therapies • Immunotherapy: Pembrolizumab (KEYNOTE-522), atezolizumab (IMpassion) • ADCs: Trastuzumab deruxtecan (DESTINY-Breast trials) • PI3K/mTOR/AKT inhibitors under evaluation • Molecular-driven therapy gaining prominence

10. Response Assessment & Surveillance • Clinical and imaging evaluation post-NAC • MRI most accurate for residual disease estimation • ctDNA and molecular monitoring emerging as predictive tools • Surveillance: 6–12 monthly for first 5 years

11. Guideline Overview (NCCN 2025 / ESMO 2024) • Multimodal approach: NAC → Surgery → RT → Systemic therapy • pCR drives adjuvant treatment decisions • Immunotherapy recommended for TNBC (PD-L1+) • HER2+ dual blockade standard in NAC

12. Future Directions & Key Takeaways • Precision oncology integrating molecular and immune biomarkers • De-escalation strategies for pCR achievers • ADCs and immunotherapy redefining post-neoadjuvant space • Multidisciplinary collaboration remains cornerstone