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Triple Negative Breast Cancer

Abbreviations. Triple negative (TN)Basal phenotype/basal-like (BP/BL)Basal typeBreast Cancer (BC). Definition. TN: immunophenotypic descriptionER (-)PR (-)Her-2/neu (-)10-17% of all breast cancers, depending on the thresholds of tests. Definition. Basal phenotype/basal-like (BP/BL)Still an i

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Triple Negative Breast Cancer

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    1. Triple Negative Breast Cancer R5??? Feb. 22, 2008

    2. Abbreviations Triple negative (TN) Basal phenotype/basal-like (BP/BL) Basal type Breast Cancer (BC)

    3. Definition TN: immunophenotypic description ER (-) PR (-) Her-2/neu (-) 10-17% of all breast cancers, depending on the thresholds of tests

    4. Definition Basal phenotype/basal-like (BP/BL) Still an immunophenotypic description Presence of basal cytokeratins and/or myoepithelial markers Basal type Based on gene expression profiles identified by mircroarray analysis

    5. Interrelationships

    6. Molecular Portraits of BC Classify 45 patients into subtypes via distinct gene expression patterns

    7. Basal V.S. Luminal

    8. The So-called Basal Type

    9. Molecular Typing and Survival

    10. How is Basal Type BC Like?

    11. Morphology and Phenotype Almost all negative of ER/Her-2 50-60% EGFR(+) >80% p53 expression High grade, high mitotic rate Pushing border, central necrosis zone Metaplastic or medullary feature

    12. TN and Basal Type BC

    13. Similar Clinical Implications Younger age Interval onset breast cancer African American Shorter disease free survival and disease specific survival Aggressive behavior with metastasis

    14. TN and BP not Synonym TN: heterogeneous group Small part Normal breast like Adenoid cystic carcinoma Medullary BP: also heterogeneous BRCA1 mutation Small part express ER Myoepithelial differentiation

    15. California Cancer Registry

    16. Early Relapse

    17. LN(+) or LN(-)

    18. CK5/6 and/or EGFR: Poor Survival

    19. Peak Recurrence in First 3 Yrs

    20. Higher Distant Metastasis

    21. TN Paradox – Better Response

    22. TN Paradox – Poorer Survival

    23. Similar Study Korean study 145 stage II/III breast cancer Neoadjuvant chemotherapy with Docetaxel + doxorubicin TN: others RR: 83%: 62.2% pCR: 17%: 3.1% Survival: still inferior

    25. Interrelationships

    27. BRCA1 Are Basal-like BC >80% BRCA1 germline mutation are TN and CK5/6 positive Also young age, high grade, central necrosis

    28. BRCA 1 Dysfunction in BLBC

    29. BRCA 1 Dysfunction in BLBC

    30. Link BRCA1 to Therapy

    31. BRCA1 Mediate Paclitaxel Induced Apoptosis

    32. Also in Vincaloids

    33. Differential Role in Other Agents The presence of BRCA1 inhibit the toxicity of bleomycin and cisplatin BRCA1 dysfunction: susceptible to DNA cross-link defects

    35. Treatment of TN Breast Ca. No standard therapies Lack of hormone, lack of Her-2/neu targeting agents BRCA1 dysfunction may be a target Cisplatin- DNA cross-link DNA repair- PARP1 inhibitor

    36. MAPK and Akt Pathways

    37. Ongoing Trials

    38. Thanks For Your Attention!

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