biomarcadores en cáncer de mama: de la evidencia a la ... · de la evidencia a la asistencia joan...
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Biomarcadores en cáncer de mama:
de la evidencia a la asistencia
Joan Albanell
Hospital del Mar, Hospital del Mar
Universitat Pompeu Fabra
NCCN (2014)
ESMO (2013)
St. Gallen (2013)
ER
/PR
/HE
R2
Ki6
7
Intr
insic
subty
pes
Oncoty
peD
X
Mam
maprint
Oth
er
pla
tform
s,
NG
S
+++
+++
+++
+
++
++
+
+
++
+++
+
+
HER2 FALSE NEGATIVE
HER2+++
Courtesy JM. Corominas (quality control SEAP)
A good therapy starts with a good diagnosis
- Identification of labs that do not provide
adequate results ?
- Acreditation ?
A good therapy starts with a good diagnosis
Evolving Classification of Breast Cancer
Clinical classification (protein expression)
Intrinsic subtype (RNA expression)
Integrative clusters (DNA/RNA)
Next-Generation Sequencing (NGS)
Comparación clasificación HER2 con
criterios ASCO/CAP 2007 vs 2014
(Salido et al. ESMO 2014)
• Using the HER2 update ISH recommendations, we observed an
increase in the number of inconclusive cases (5% vs 11%), thus
causing the theoretical need to repeat the ISH technique on another
sample or if remains inconclusive to perform an alternative test (IHQ).
Most of these cases showed polysomy (4-5 copies) of chromosome 17
and were negative by IHC.
• An increase in the number of positive cases was observed (18% vs
23%), mainly due to cases with ≥6.0 signals and to the decrease in the
ratio of ≥2 instead 2.2.
• Among the equivocal ISH results by the 2013 criteria, 3% were
confirmed as positive result by IHC (3+), which would be considered
as a false-negative by the 2007 criteria.
Comparación clasificación HER2 con
criterios ASCO/CAP 2007 vs 2014
(Salido et al. ESMO 2014)
32%
Evolving Classification of Breast Cancer
Clinical classification (protein expression)
Intrinsic subtypes (RNA expression)
Integrative clusters (DNA/RNA)
Next-Generation Sequencing (NGS)
Intrinsic Subtypes
Perou et al. Nature 2000; 406: 747
St. Gallen Consensus 2013
Evolving Classification of Breast Cancer
Clinical classification (protein expression)
Intrinsic subtype (RNA expression)
Integrative clusters (DNA/RNA)
Next-Generation Sequencing (NGS)
DNA Copy number gain
DNA Copy number loss
Over or under expressed
genes
TOP 10 mutated genes by
Exome sequencing in IntClust10
(TCGA, Nature 2012)
Evolving Classification of Breast Cancer
Clinical classification (protein expression)
Intrinsic subtype (RNA expression)
Integrative clusters (DNA/RNA)
Next-Generation Sequencing (NGS)
Craig et al MCT 2013
Firmas multi-genéticas pronósticas y/o predictivas
ATAC & BIG 1-98 JNCI 2012
26
Treatment Recommendation Shifted in a
Third of the Patients After Oncotype DX Testing
11.2% HT alone to CHT
20.6% CT to HT alone
HER2+ (15-20%)
RH+ (60-70%)
TRIPLE NEGATIVO
(RHs- y HER2 -) (10-15%)
Biomarcadores en cáncer de mama: práctica clínica
RE, RP, HER2: controles SEAP y
criterios ASCO/CAP
Ki67?
Subtipos intrínsecos (PAM50): base
de selección en ensayos clínicos
Plataformas
Valor pronóstico: Oncotype DX,
PAM50, Endopredict, Mammaprint
Valor predictivo QT (RE+,HER2-):
- todas alguna forma de evidencia
retrospectiva
- evidencia de ensayo
retro-prospectivo: Oncotype DX