Ergebnisse der Translationalen Forschung der GBG

Ergebnisse der Translationalen Forschung
der GBG - Review of the year
Prof. Dr. Volkmar Müller
Klinik für Gynäkologie, Brustzentrum am UKE
Universitätsklinikum Hamburg-Eppendorf
Kann ein Genexpressionstest zusätzliche Informationen nach
neoadjuvanter Chemotherapie bei Hormonrezeptor-positiven
Patientinnen liefern?
Aims of the study:
1) Evaluation of the gene expression test EndoPredict (EP and
EPclin) performed on residual tumor specimen after NACT for
predicting prognosis in patients (pts) with ER+/HER2- BC who
did not achieve a pCR.
2) Comparison of its prognostic power with the CPS-EG score that
combines tumor stage (pre- and post NACT), grade and ER
status.
Vergleich Endopredict am OP-Präparat mit dem CPS-EG Score
Schlussfolgerung
 In this prospectively planned biomarker study we show that the
information in the hybrid clinico-molecular EPclin score is also
prognostic for DFS and OS after NACT.
 EPclin provides additional prognostic information to CPS-EG.
 This approach can be used to assess prognosis after NACT in the
luminal non-pCR patient population, and select patients for postNACT therapies, e.g. treatment with CDK4/6 inhibitors.
Endopredict am OP-Präparat liefert zusätzliche
Informationen zu CPS-EG Score -> wichtig für
postneoadjuvante Studien
Dezember: Auf nach San Antonio
Ziel
 The aim of the study is to compare the pattern of
somatic mutations between pregnant and nonpregnant patients with breast cancer using a dataset of
pregnant patients enrolled in BCP study and nonpregnant controls obtained from TCGA database
Gibt es genetische Unterschiede im Tumor zwischen
Mammakarzinomen innerhalb und außerhalb der
Schwangerschaft?
Schlussfolgerung
 Conclusion: Overall the mutational landscape does not
seem to be different between pregnant patients and
no-pregnant controls
Nein!
Neoadjuvante Therapie
HRD-Defizit als prädiktiver Faktor für das
Ansprechen aus Carboplatin?
HRD in Geparsixto: Fragestellung
 To determine whether HRD can predict the effect of
carboplatin on survival in TNBC subgroup from
GeparSixto trial, we correlated the HRD status to the
event free survival (EFS).
Kann ein Defizit in der der homologen DNA-Reparatur
(HRD) ein besseres Ansprechen auf Carboplatin
vorhersagen?
HRD in Geparsixto: Schlussfolgerung
 Within the GeparSixto study the HR-deficiency (either HRD
score high or BRCA mutation) was in general associated with a
higher pCR rate and an improved EFS.
 The effect on EFS of adding carboplatin could not be predicted
by the HRD score in this underpowered study.
 However, the results can help to understand the role of HRdeficiency and the value of the HRD score in TNBC especially in
patients without BRCA mutation.
Defizit in der der homologen DNA-Reparatur (hoher
HRD-Score oder BRCA-Mutation) höhere pCR-Rate und
besseres Rezidivfreies Überleben, aber bessere
Wirksamkeit von Carbo lässt sich nicht vorhersagen
Rolle zirkulierender Tumorzellen bei neoadjuvanter
Therapie
Projektvorschlag 2005
Rolle zirkulierender Tumorzellen bei neoadjuvanter
Therapie
Projektvorschlag 2005
Erste Publikation 2010
Rolle zirkulierender Tumorzellen bei neoadjuvanter
Therapie
San Antonio Breast Cancer Symposium – December 6-10, 2016
Data collection
Letter of intent
#2,000 potentially eligible pts
from 18 centers
call for
data
2 centers
off study
2,239 pts data received
data
cleaning
83 excluded
2,156 individual patients
21 studies
746 Patientinnen aus GBG-Studien!
16 centers
This presentation is the intellectual property of the presenter. contact [email protected] for permission to reprint/ distribute.
San Antonio Breast Cancer Symposium – December 6-10, 2016
CTC before NCT & Overall Survival
Stratified p value <.0001
months
Kürzeres Gesamtüberleben bei Nachweis von Tumorzellen im Blut vor
neoadjuvanter Chemotherapie
N pts
1175
199
59
% events
9.8%
10.6%
23.7%
3-4 CTC
47
29.8%
≥ 5 CTC
93
46.2%
0 CTC
1 CTC
2 CTC
Hazard Ratio
1
1.09 [0.65-1.69]
2.63 [1.42-4.54]
3.84 [2.08-6.66]
6.25 [4.34-9.09]
This presentation is the intellectual property of the presenter. contact [email protected] for permission to reprint/ distribute.
San Antonio Breast Cancer Symposium – December 6-10, 2016
Overall clinical validity (single point; ≥2 CTC)
Multivariate analyses
Time point
CTC at baseline
(landmark analysis)
CTC [-5;0]w
before surgery
(landmark analysis)
OS
DDFS
LRFI
HR
p
HR
p
HR
p
4.19
<.0001
3.79
<.0001
3.20
<.0001
[2.97-5.88]
2.56
[1.45-4.23]
[2.84-5.03]
.0020
2.69
[1.67-4.12]
[1.93-5.19]
<.0001
1.05
[0.32-2.55]
Nachweis von Tumorzellen im Blut vor neoadjuvanter Chemotherapie
unabhängiger und zusätzlicher Prognosefaktor
This presentation is the intellectual property of the presenter. contact [email protected] for permission to reprint/ distribute.
.92
San Antonio Breast Cancer Symposium, December 6 -10, 2016
Evaluation of tumor-infiltrating lymphocytes (TILs) as
predictive and prognostic biomarker in different
subtypes of breast cancer treated with neoadjuvant
therapy
- a metaanalysis of 3771 patients
Carsten Denkert, Gunter von Minckwitz, Silvia Darb-Esfahani, Barbara Ingold-Heppner,
Frederick Klauschen, Jenny Furlanetto, Berit Pfitzner, Jens Huober, Wolfgang Schmitt,
Jens-Uwe Blohmer, Sherko Kümmel, Knut Engels, Bianca Lederer, Andreas
Schneeweiss, Arndt Hartmann, Christian Jackisch, Michael Untch, Claus Hanusch,
Karsten Weber, Sibylle Loibl
This presentation is the intellectual property of the author/presenter. Contact them at
[email protected] for permission to reprint and/or distribute.
Fazit
 Auch im letzten Jahr starke Präsenz translationaler Forschung
der GBG auf internationalen Kongressen
Verdienst vieler Beteiligter:
•
•
•
•
Ärzte
Pflege
Studienteams
Patientinnen
GBG Subboard Translationale Forschung