Mammaprint
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Mammaprint Mammaprint
Carlos Andrés Ossa Gómez Cirugía Oncológica de Mama
/Mastología
Carlos Andrés Ossa Gómez Cirugía Oncológica de Mama
/Mastología
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Dilema del tratamiento Dilema del tratamiento
Choices of 40 experts world-wide
61 años postmenopausica en BCG Ductal Infiltrante G2Ganglio negativopT = 0.9 cm ER(+) and PR negativoHER2 (-)
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De 100 Mujeres con cancer de mama De 100 Mujeres con cancer de mama
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Solo 25 % desarrollaran metastasis a distancia Solo 25 % desarrollaran metastasis a distancia
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Pero estamos tratando el 75 % de los pacientes con quimioterapia
Pero estamos tratando el 75 % de los pacientes con quimioterapia
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Lo cual significa que el 50% de las ptes estan recibiendo quimioterapia que quizas no necesitan
Lo cual significa que el 50% de las ptes estan recibiendo quimioterapia que quizas no necesitan
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78 breast tumors (‘83-’94)patients < 55 yearstumor size < 5 cm
lymph node negative (LN0)no adjuvant therapy
no distant metastasesin at least 5 years (n=44)
distant metastases< 5 years (n=34)
Prognosis Reporter Genes
Prediccion del riesgo de la enfermedad basado en perfiles de
expresion genetica
Prediccion del riesgo de la enfermedad basado en perfiles de
expresion genetica
van´t Veer et al., Nature 415, p. 530-536, 2002
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threshold set with 10% false negatives91 % sensitivity, 73% specificity
70 Gene Prognosis ProfileSupervised analysis
van´t Veer et al., Nature 415, p. 530-536, 2002
70 significant prognosis genes
Tum
or s
ampl
es
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Agendia’s breast cancer prognosis test:MammaPrint
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Estudio de validacion externa
Buyse et al. (2006)
JNCI. 98, 1183-1192.
Estudio de validacion externa
Buyse et al. (2006)
JNCI. 98, 1183-1192.
302 patients
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Validacion externa independiente :
Buyse et al JNCI 2006
Alto riesgo clinicoAdjuvant on line! N=22273%
Bajo riesgo clinico Adjuvant on line! N=8027%
27% microarray
Bajo riesgo
35% microarrayAlto riesgo
>30% casos discordantes
Sub-tratadas !
Sobre- tratadas !
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High reproducibility of microarray experiments (99%)
Glas et al, BMC Genomics 2007
Reproducibility; repeat of the experiment Reproducibility; 2 samples, 7 month period
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MammaPrint: extensive regulatory approvals
MammaPrint aprovada por la FDA MammaPrint aprovada por la FDA
CAP Acreditada Pathologists CAP Acreditada Pathologists
s
s
ISO 17025 acreditacion europea
CLIA aprobacion para uso en pacientes
EEUUA
ISO 17025 acreditacion europea
CLIA aprobacion para uso en pacientes
EEUUA
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Caracteristicas adicionales del Mammaprint
Pacientes con 1-3 ganglios positivos
Caracteristicas adicionales del Mammaprint
Pacientes con 1-3 ganglios positivos
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Validacion en pacientes con 1-3 Ganglios Positivos
Validacion en pacientes con 1-3 Ganglios Positivos
Milan and NKI series 241 patientsMilan EIO (B Viale): 1994-1998NKI series: 1984-199580% treated adjuvant chemo and/or hormonal therapy
Median Follow Up:Milan: 8.97 years (0-10.9)NKI : 10.4 years (1.6-21.2)
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Multivariate HR 6.59 (95% CI 1.71 to 25.45; p = 0.006)
N=241 ptes G(+) 1-3Milan & NKI
Validacion en pacientes con 1-3 Ganglios Positivos
Validacion en pacientes con 1-3 Ganglios Positivos
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Meta-analysis MammaPrint in HER2+ tumorsHER2 positive IHC/CISH n=169
Knauer et al, SABCS 2008 #4171
(n=169)
HRmultivar 5.4 (1.3-23; p=0.024)
(n=90)
HRmultivar 4.8 (1.1-20; p=0.033)
Is there a HER2 positive - low risk group (~15% of HER2 pos)that could receive only endocrine and targeted therapy?
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MammaPrint predicts response to neo-adjuvantchemotherapy
- 2 clinical trials- T-stage >3 cm and/or LNplus (SNB/FNA)
- ultrasound guided 14 gauge biopsies- MRI imaging- Pathology
pCR
pCR + near pCRMarieke Straver et al.,Br Cancer Res and Treatm,2009
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Neo-adjuvant Standard Chemotherapyand MammaPrint Signature
- pacientes con señal de alto riesgo por Mammaprintmostraron una alta quimiosensibilidad
-Todas las pCR se encontraron en el grupo de alto riesgo
Pacientes con señales de alto riesgo tienen beneficio clinico con quimioterapia
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No Recurrences in the Good Prognosis Group
MammaPrint:
Good Prognosis(N=23)
Poor Prognosis(N=144)
Marieke Straver et al.,Br Cancer Res and Treatm,2009
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Meta-analysis of chemo benefit of MammaPrint high risk group
Knauer et al,2009
Median follow-up 7.08 years (0.01 – 25.22)
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Medicina Personalizada: multiples respuesta en un chip unico
pronostico?
Puede el tumor responder a herceptin?
Puede el tumor tener respuesta
cruzada a quimioterapia?
Existe una mutacion en el BRCA?
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ASSESS clinical RISK AND MammaPrint RISKASSESS clinical RISK AND MammaPrint RISK(adjuvant!online & MammaPrint)(adjuvant!online & MammaPrint)
BOTH HIGH BOTH HIGH RISKRISK
DISCORDANTDISCORDANTRISKRISK
BOTH LOW BOTH LOW RISKRISK
RANDOMIZERANDOMIZEdecision-makingdecision-making
ChemotherapyChemotherapy No chemotherapyNo chemotherapy
Use MammaPrintUse MammaPrintUse clinical riskUse clinical risk
MINDACT study designMINDACT study design
6000 patients, <70 YRS, 1-3 POS NODES6000 patients, <70 YRS, 1-3 POS NODES
highhigh low
low
55% 35% 10%
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Discusión Discusión
Ventajas Ventajas • Menor Costo que el
Oncotype DX• Clasificación intrínseca de
los tumores (luminal A-B-Her2 enriched,basal like)
• Permite Correlación Con La inmunohistoquimica
• Hasta tumores de 5 cms, Rh negativo.
• Menor Costo que el Oncotype DX
• Clasificación intrínseca de los tumores (luminal A-B-Her2 enriched,basal like)
• Permite Correlación Con La inmunohistoquimica
• Hasta tumores de 5 cms, Rh negativo.
Desventajas • Tejido Fresco Congelado• Hasta el 10 % de la
muestras Rechazadas.• Perfiles Geneticos Europeos
Diferentes a los Nuestros. • La Fuerza de los estudios es
debil retrospectivos.•
• Tejido Fresco Congelado• Hasta el 10 % de la
muestras Rechazadas.• Perfiles Geneticos Europeos
Diferentes a los Nuestros. • La Fuerza de los estudios es
debil retrospectivos.•
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