NEOADYUVANCIA EN CÁNCER DE MAMA TRIPLE NEGATIVO

Mª José Echarri

Oncología Médica

Hospital Severo Ochoa

08/06/2018

DEFINICIÓN

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

http://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjxibT5yuPKAhUBOxoKHT3-BMQQjRwIBw&url=http://mama2punto0.cl/consejos-para-afrontar-el-regreso-la-rutina/&psig=AFQjCNHzUqv9cAFLCF-CPX-qPNtoEB8kiw&ust=1454863456098170

¿QUÉ ESQUEMA DE QUIMIOTERAPIA ELEGIR EN NEOADYUVANCIA TRIPLE NEGATIVO?

http://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiMp5KI_9bKAhUGNhoKHYY0DU4QjRwIBw&url=http://akifrases.com/frase/135215&psig=AFQjCNHBTls-G8M0smgEe6mrh0AYw_AA9Q&ust=1454430645987306

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