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