neoadyuvancia en cÁncer de mama triple negativo … · adyuvancia y cmm neoadyuvancia ....
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NEOADYUVANCIA EN CÁNCER DE MAMA TRIPLE NEGATIVO
Mª José Echarri
Oncología Médica
Hospital Severo Ochoa
08/06/2018
Recommendation
Optimal algorithm
for ER/PgR testing
Positive for ER or PgR if finding of ≥ 1% of tumor cell nuclei
are immunoreactive
Negative for ER or PgR if finding of < 1% of tumor cell
nuclei are immunoreactive in the presence of evidence that
the sample can express ER or PgR (positive intrinsic
controls are seen)
JCO June 1, 2010, Vol 28:16 Allred Mol Oncol 2010
FISH, fluorescence in situ hybridisation; IHC, immunohistochemistry
Centromeric probe for chromosome 17
HER2 gene
HER2 protein evaluated by IHC1
IHC is scored on a 0–3+ scale based on staining intensity and completeness of
membrane staining
Definition: HER2-positive tumours are scored 3+ by IHC, or are FISH-positive (HER2 gene copy number per cell >6 or HER2:chromosome 17 ratio >2.2)2
Amplified
Figures adapted from: 1. Hicks DG & Tubbs RR. Hum Pathol 2005; 36:250–261;
2. Wolff AC, et al. Arch Pathol Lab Med 2007; 131:18–43.
IHC 0 IHC 1+
IHC 2+ IHC 3+
Non-amplified
Non-amplified Amplified
100X
630X
DEFINICIÓN TRIPLE NEGATIVO
Cell 2014 Hoadley
80-85%
10-15%
Glycoprotein Non-metastatic Melanoma B (gpNMB) is a negative prognostic marker that overexpressed in 40% of TNBC, gpNMB can promote angiogenesis, migration, invasion, and metastasis
By definition, overexpression of gpNMB is positivity of more than 5% of cell in IHC.
Trop2, a transmembrane glycoprotein, has emerged as a biomarker for targeted cancer therapy since it is overexpressed in 80% of triple negative breast cancer (TNBC) patients.
Trop2
JAK2
Trop2 gpNMB
Immune-activated Immune-inactivated
NEOADYUVANCIA
Adyuvancia y CMM
Neoadyuvancia
NEOADYUVANCIA: cambios recientes
-Tumores localmente avanzados?: estadio II -Subtipos “quimiosensibles” -Pacientes buen estado general -”Fit” quimioterapia -Ensayos clínicos comparado QT neoadyuvante frente adyuvante -Boom ensayos clinicos en neoadyuvancia según subtipo tumoral -Endpoint ensayos: pCR (marcador subrrogado de SLP)
NEOADYUVANCIA: cambios recientes
Neoadjuvant Therapy for Early-Stage Breast Cancer: Current Practice, Controversies, and Future Directions.
Oncology 2016
PREDECIR BENEFICIO A LARGO TRAS NEOADYUVANCIA
Neoadjuvant Therapy As a Platform for Drug Development: Current Controversies and Regulatory Perspectives
AGO-1
ECTO
EORTC 10994
GEPAR-DUO
GEPAR-TRIO
GEPAR-QUATTRO
NSABP-B18
NSABP-B27
NOAH
PREPARE
TECHNO
Slide 18
¿QUÉ ESQUEMA DE QUIMIOTERAPIA ELEGIR EN NEOADYUVANCIA TRIPLE NEGATIVO?
Cell
survival
Base Excision Repair
Synthetic Lethality: Selective effect of PARP-1 inhibition on cancer cells
with BRCA1 or BRCA2 mutation
Homologous Recombination
DNA Damage
PARP
Inhibitor
BRCA
Mutation
Cancer cell
death
•Neoadyuvancia: GeparSepto vs ETNA
Paclitaxel vs Nab-Paclitaxel
Slide 12
Presented By Ruth O''Regan at 2018 ASCO Annual Meeting
ESPAÑA
ETNA (Evaluating Treatment with Neoadjuvant Abraxane) <br />randomized phase III study comparing <br />neoadjuvant nab-Paclitaxel (nab-P) versus Paclitaxel (P) <br />both followed by anthracycline regimens in women with HER2-negative <br />high-risk breast cancer: A Michelangelo study<br />in collaboration with GEICAM and BCRC-WA
Presented By Luca Gianni at 2016 ASCO Annual Meeting
Scheme of the Phase III randomized ETNA trial
Presented By Luca Gianni at 2016 ASCO Annual Meeting
Primary endpoint: pCR rate
Presented By Luca Gianni at 2016 ASCO Annual Meeting
Triples negativos: 37 vs 41%
Conclusions
Presented By Luca Gianni at 2016 ASCO Annual Meeting
Entonces……….
KEYNOTE 522: Addition of pembrolizumab to standard chemotherapy pre-operatively
Presented By Ruth O''Regan at 2018 ASCO Annual Meeting
“Adjuvant” chemotherapy in patients with residual TNBC (EA 1131)
Presented By Ruth O''Regan at 2018 ASCO Annual Meeting
SWOG 1418: Adjuvant pembrolizumab in TNBC
Presented By Ruth O''Regan at 2018 ASCO Annual Meeting
Feasibility study of adjuvant enzalutamide in AR+ TNBC
Presented By Ruth O''Regan at 2018 ASCO Annual Meeting
OlympiaA: Adjuvant olaparib in BRCA-mutation carriers with HER2-negative breast cancer
Presented By Ruth O''Regan at 2018 ASCO Annual Meeting