d coeffic adjuvant ct for t1ab jerusalem 2014
DESCRIPTION
TRANSCRIPT
Adjuvant chemotherapy for T1ab breast cancer in 2014 ?
David Coeffic Cancer Ins@tute of Reims– Polyclinique
Courlancy
What we talk about ?
• pT1ab (≤ 1 cm)
• pN1 and pNmic are excluded
T1abN0 : is it a real problem in term of prognosis?
• The number of clinical events could be jus@fied specific treatment ?
• In other words, there is some clues that jus@fy to select predic@ve sub-‐type for treatment ?
Historic considera@on
We started, and it's a « shame », to be interested in T1abN0 from the @me there was a talk about Her2 !!
But several studies published in the last decade strongly support the fact that the metasta@c poten@al of breast tumors may be present a very early event, even though the primary breast tumor is not detectable by imaging (Engel, 2003 ; Van’t Veer, 2002 ; Schmidt-‐Ki:ler 2003 ; Husemann 2008 et Podsypanina 2008).
Press MF. et al. JCO 1997;15(8):2894-2904 Temps jusqu’à récidive (mois)
Pro
babi
lité
de s
urvi
e
Tumor size
Events exist !!!
§ Retrospective mulicentric study (US) § 382 tumoral sample (from surgery) § N0 breast cancer § Diagnosis < 1990 § No adjuvant chemotherapy § FISH analysis for HER2
We have found events in T1ab ! • n = 965, 10 % of HER2+ • More T1a than T1b are HER2+ • No pa@ents received Chemotherapy or Trastuzumab • Median follow-‐up: 6.2 years
Gonzalez-Angulo AM. et al – J Clin Oncol 2009
Time to diagnosis (months)
DFS
Time to diagnosis (months)
Met
asta
tic D
FS
Events exist, even with treatment !!
• T1abc pN0 N = 2 026 -‐ T1a-‐b = 328 and T1c HR 1.71 (p = 0.01) DFS -‐ 67 % = adjuvant chemotherapy HR 2.03 (p = 0.003) OS -‐ Median Follow-‐up: 12.4 years
Chia S. et al. J Clin Oncol 2008;26:5697-‐5704
All patients
Time (years)
Surv
ie s
ans
réci
dive
(p
roba
bilit
é)
Patient without adjuvant chemotherapy
Time (years)
Surv
ie s
ans
réci
dive
(p
roba
bilit
é)
Events exist, even with treatment, even for HER2…
Popula@on T1a-‐b = 328, HER2+ : 10 % (n = 32)
Chia S. et al. J Clin Oncol 2008;26:5697-‐5704
T1a-b
Time (y)
DFS
OS
T1a-b
Time (y)
DFS
T1a-b, Without adjuvant chemotherapy
Time (y)
In conlusion
• The number of event according to the retrospec@ve study is located between 5 and 10 % in no pretreated pa@ents
• Events exist, even in pa@ents treated, confirming the requirement for op@mizing treatment
• There is some prognos@c factors that seem obvious now, some of which are also predictors
Summary but not limited, prognos@c factors highlighted on retrospec@ve series, for DFS Red: posi@ve in mul@variate analysis, Yellow : posi@ve in univariate analysis
Author Journal
Year # Fol Feature
5- years
Her 2 + Triple N ER - Age Grade KI 67 Embol Node
Livi Cancer
2012 704 <35
Kwon BMC
2010 375 61 m
Monocentric T1Mic
3 M+ <35 1 Cut off
14 %
Cancello Breast
2011 1691 DFS =
92,5 %
Cut off 14 %
Theriault JCO
2012 1012 No treated < 35 vs
> 50
Hanrahan JCO
2007 51246 SEER registry <50 Grade
III > 6
Fisher JNCI
2001 235 Including T1c 50 ans
Wood Ann Surg
2002 282 Monocentric Nomogramme
2 M+ at 10
y Grade
cIII
Colleoni Ann Oncol
2004 425 Including T1 Mic Cut off
20 %
Kaplan 2009 110 4,2 y
DFS = 89 %
• Age and prolifera@on are the major and universal prognos@c factors. • Clinical Triple nega@ve is also a major factor • Molecular factors that are predictors are somewhat interrelated
à To go further, it is urgent to have a more individualis@c approach based on molecular approach
« Doxa » of @me? For example, three paths :
• NCCN 2014 • Permanent publica@on screening • Based on the level of evidence
• Saint Gallen 2011 • Scien@fic and intellectualized approach • Only a consensus approach base on expert opinions
• French experts consensus 2011 (F Penault Llorca et al.) • A consensus based on a exhaus@ve bibliographic screening
HER 2 néga@ve
HER2 posi@ve
Saint Gallen : a molecular approach
French expert reviews for tumors Her 2 +
** For grade 1 tumors and expressing strongly HR: request a review of HER2 status by FISH
Treatment of patients with breast cancer without lymph node involvement, HER2 is overexpressed
< 1 cm > 1 cm HR + ** HR - HR + ER-
All grade Chemotherapy + Trastuzumab § < 35 ans or § High proliferation (KI67, MI) or § and/or grade 2-3 § and/or embols +/- Hormonothérapie
Chemotherapy + Trastuzumab
Hormonotherapy Chemotherapy +
Trastuzumab
Chemotherapy + Trastuzumab
Penault-Llorca F et Coeffic D. Bull Cancer 2011; Jul;98(7):807-25.
A synthesis ? Size T1a T1b
Her 2+ RH - Her 2+ RH +
Luminal A Luminal B TN Her 2+ RH -
Her 2+ RH +
Luminal A
Luminal B
TN
NCCN 2014 No tt * HT*
HT *
HT * No tt * TZ + CT HT TZ+CT
HT CT according to Oncotype Dx
HT CT according to Oncotype Dx
CT
Saint Gallen 2011
No tt HT HT HT CT TZ + CT HT TZ + CT
HT CT according to Oncotype Dx and UPA/P1
HT CT according to Oncotype Dx and UPA/P1
CT
French Consensus Penault Llorca 2011
TZ + CT HT TZ + CT according to age, KI67, MI,grade embols
No tt TZ +CT HT TZ + CT according to age, KI67, MI,grade embols
CT
INCA 2012 No answer No answer No answer No answer
* CT si Mic
Size T1a T1b
Her 2+ RH - Her 2+ RH +
Luminal A Luminal B TN Her 2+ RH -
Her 2+ RH +
Luminal A
Luminal B
TN
NCCN 2014 No tt * HT*
HT *
HT * No tt * TZ + CT HT TZ+CT
HT CT according to Oncotype Dx
HT CT according to Oncotype Dx
CT
Saint Gallen 2011
No tt HT HT HT CT TZ + CT HT TZ + CT
HT CT according to Oncotype Dx and UPA/P1
HT CT according to Oncotype Dx and UPA/P1
CT
French Consensus Penault Llorca 2011
TZ + CT HT TZ + CT according to age, KI67, MI,grade embols
No tt TZ +CT HT TZ + CT according to age, KI67, MI,grade embols
CT
INCA 2012 No answer No answer No answer No answer
Area of consensus
* CT si Mic
Size T1a T1b
Her 2+ RH - Her 2+ RH +
Luminal A Luminal B TN Her 2+ RH -
Her 2+ RH +
Luminal A
Luminal B
TN
NCCN 2014 No tt * HT*
HT *
HT * No tt * TZ + CT HT TZ+CT
HT CT according to Oncotype Dx
HT CT according to Oncotype Dx
CT
Saint Gallen 2011
No tt HT HT HT CT TZ + CT HT TZ + CT
HT CT according to Oncotype Dx and UPA/P1
HT CT according to Oncotype Dx and UPA/P1
CT
French Consensus Penault Llorca 2011
TZ + CT HT TZ + CT according to age, KI67, MI,grade embols
No tt TZ +CT HT TZ + CT according to age, KI67, MI,grade embols
CT
INCA 2012 No answer No answer No answer No answer
Area of disagreement
* CT si Mic
Problems are not yet solved!
• The ques@ons that we will live • Her2 tumors: should we take into account the size and / or
the HR status ?
• TN: What are the predictors of efficacy to chemotherapy? For which sub-‐group?
• Beyond the size, which predictors for chemotherapy in luminal ?
Her 2 + disease
Decision criterias in the « real life » for T1ab Her 2
Trastuzumab (n=93)
No Trastuzumab (n=112)
P value (Fisher test)
T1a T1b
16 (17%) 77 (83%)
36 (32%) 76 (68%)
0.016
Grade 1 Grade 2-3
3 (3%) 89 (97%)
17 (16%) 90 (84%)
0.004
HR + HR -
40 (43%) 53 (57%)
81 (72%) 31 (38%)
<0.001
MI =1 MI =2-3
24 (40%) 36 (60%)
58 (67%) 28 (33%)
0.001
Embols No Yes
72 (78%) 20 (22%)
95 (88%) 13 (12%)
0.085
* Log-‐rank test was used
Julien Peron. Study AERIO/UNICANCER, SABCS 2011.
HER 2 + as a prognos@c factor in T1ab ?
Retrospec@ve studies, Her 2 breast cancer T1, N0, M0.
Study Only T1a-b
# T1a T1b
HER2+ (%)
Median follow-up
(Y)
Adjuvant treatment
Press No 382 ? (Fish) ? No
Black No 27 47
100 5.6 ?
Joensuu No 49 264
12 9.5 No
Tavey No 230
6.9 6.5 ?
Chia No 103 225
6.4 12.4 67 %
Curigliano Yes 85 65
100 4.5 Yes
Gonzalez-Angulo Yes 323 642
10 6.2 No
Peron San Antonio 2011
Yes 52 153
100 ? 40 %
Rouanet San Antonio 2011
Yes 131 572
5,9 ? No
Events exist!!!
§ Retrospective Finnish study.
§ 852 patients with pT1N0M0 breast cancer between 1991 and 1992.
§ Multivariate analysis § Median Follow-up : 9,5
years. § Only 5 % received
adjuvant chemotherapy
Joensuu H. et al. Clin. Cancer Res. 2003;9:923-930
Années de suivi Années de suivi
Années de suivi Années de suivi
Sur
vie
sans
mal
adie
à
dist
ance
S
urvi
e sa
ns m
alad
ie à
di
stan
ce
T1ab T1c
IHC
CISH
HER2 is a poor prognostic factor even when the tumor is small (T1ab, T1c).
HER2 expression is the major risk factor for recurrence in pT1a-‐b, NO breast cancer:
Clinical implicaAons from a French regional populaAon-‐based study of 703 paAents
Rouanet P, Roger P, Daures JP, Rousseau E, Romieu G, Mathieu A, Cretin J, Barneon G, Granier M, Maran-
Gonzalez A, Thibault S. Boissiere F, Bibeau F.
ONCO Languedoc-Roussillon Network
Disease Recurrence • 5-‐year DFS rates were 74% and 95% in pa@ents with HER2-‐posi@ve and
HER2-‐nega@ve tumors, respec@vely (p<0.0001)
• According to the immunohistochemical phenotype DFS-‐5 years were • 95% for ER+/PR+/HER2-‐ (n=614/87%) • 91% ER-‐/PR-‐/HER2-‐ (n=47/6.7%) • 69% ER+/PR+/HER2+ (n=25/3.5%) • 81% ER-‐/PR-‐/HER2+ (n=17/2,4%)
• In univariate analysis, HER2 posi@ve tumors (p=0.017), phenotype classifica@on (p=0.02) and adjuvant treatment (p=0.013) were significant prognos@c factors
• In mul@variate analysis, only pa@ents with HER2+ tumors had higher risks of recurrence (hazard ra@o [HR], 2.41; 95% CI; [1.06-‐5.53]; p<0.05) than those with HER2-‐ tumors.
Benefit of Trastuzumab in T1N0 ?
Avantage AC-TH
Avantage AC-T
1.0 0.0 2.0
Node -‐
Node +
HR -‐
HR +
Tumor size < 2cm
Tumor size ≥ 2cm
AC-‐TH vs AC-‐T
1.0 0.0 2.0
Node -‐
Node +
HR -‐
HR +
Tumor size < 2cm
Tumor size ≥ 2cm
TCH vs AC-‐T
Avantage TCH
Avantage AC-‐T
BCIRG 006 : Subgroup analysis (OS)
Slamon et al. SABCS 2006
A french retrospec@ve pragma@cal study !
o Mul@centric study
o 96 T1a-‐b, N0 invasive breast cancers o Micro invasion and mul@focal tumor are excluded
o Median size: 8 mm (2 – 10 mm)
o 25 (20 %) ≤ 5 mm
o Adjuvant treatment: for « poor prognosis » (high grade and/or HR-‐) o 40 pa@ents were treated
o 90 % (37/40) of pa@ents received chemotherapy + trastuzumab
o 7 % (3/40) of pa@ents received trastuzumab alone.
Rodriguez et al. – ASCO 2009
Rodriguez et al. ASCO 2009
40 « poor prognosis » 56 « good prognosis »
No recurrence 9 % of recurrence
Trastuzumab
§ Recurrences only in the "Good prognosis" group: 9% vs 0% § Recurrences could probably be avoided, perhaps, by an effective treatment in the "Good prognosis" group.
… pragma@cal results
Systemic Adjuvant Treatment Of T1a and T1b N0M0 HER2+ Breast Carcinomas; an
AERIO/UNICANCER Study Julien Péron1, Jean Sebastien Frenel2, Yann Vano3, Johanna Wasserman4,5,
Laurence Albiges-Sauvin4,6, Manuel Rodrigues4,7, Anne Vincent-Salomon7, Paul Cottu7 1Centre Léon Bérard , Lyon, France ; 2Centre René Gauducheau ,
Nantes, France ; 3Centre Antoine Lacassagne, Nice, France ; 4Association pour l’Enseignement et la Recherche des Internes en Oncologie ;
5Centre René Huguenin, Saint Cloud, France ; 6Institut Gustave Roussy, Villejuif, France ; 7Institut Curie, Paris, France
• Trastuzumab/CT treatment led to a lower risk of recurrence (p=0.004)
• Among 51 T1a tumors, 16 pa@ents received TZM/CT. One recurrence occurred among treated pa@ents and 3 among untreated pa@ents.
Californian registry on cause-‐specific mortality Pa@ents with breast cancer N0, T1a or T1b, HER2 +
Chew et al. J Clin Oncol 2010,28(suppl):abstract 583
All cases n = 20 188
2000 – 2004 n = 9 409
2005 – 2007 n = 10 779
HER2 Positive Negative
n (%) 3 196 (15.8)
16 992 (84.2)
n (%) 1 579 (16.8) 7 830 (83.2)
n (%) 1 617 (15) 9 162 (85)
Hormone receptors Weigh@ng factor in the management ?
Then what about the size (T1a) ?
Her + / HR +, good prognosis ?
• T1abc pN0 N = 2 026 -‐ T1a-‐b = 328 and T1c HR 1.71 (p = 0.01) DFS -‐ 67 % = adjuvant chemotherapy HR 2.03 (p = 0.003) OS -‐ Median Follow-‐up: 12.4 years
Chia S. et al. J Clin Oncol 2008;26:5697-‐5704
All patients
Time (year)
DFS
No adjuvant treatment
Time (year)
T1/RH
Time (year)
DFS
Surv
ie s
ans
réci
dive
(p
roba
bilit
é)
No reason to consider a difference between T1a and T1b, why ?
• Because the size is a con@nuous variable
• Because the size is partly a subjec@ve variable
• Because the limits of 5 mm or 10 mm were arbitrarily set
• Finally, because there are few data in bibliography…
Rakkhit R. et al. SABCS 2008
T1ab HER2 + DFS
1A : DFS / HER + or - 1B : DFS
HR : HR + et HER - Triple negative HER2 : HER2+
Mul@variate analysis
Gonzalez-Angulo AM. et al – J Clin Oncol 2009
Survie sans récidive Survie sans récidive à distance
HR 95 % IC p HR 95 % IC p
HER2 positif vs négatif 2.68 (1.44 – 5) 0.002 5.30 (2.23 – 12.62) 0.0002
RH positif vs négatif 0.41 (0.23 – 0.72) 0.002 0.59 (0.25 – 1.37) 0.219
Âge et diagnostic 0.96 (0.94 – 0.98) 0.001 0.73 (0.32 – 1.7) 0.467
Grade 3 vs grade 1-2 1.34 (0.78 – 2.41) 0.320 0.97 (0.94 – 1) 0.080
Stade Ib versus Ia 1.59 (0.91 – 2.78) 0.103 1.47 (0.68 – 3.18) 0.329
Benefit of chemotherapy / Risk ?
Cardiotoxicity
Median follow-up Patients number
12-39 mois > 4000
2 ans 1056
39 mois 116
1 an 1677
2 ans 718
2 ans 1068
2 ans 579
3 ans 216
Treatment No Trastu
Docetaxel Carbopla@n + Trastu
9 weeks an@-‐micro tubules +
trastu follow by FEC x 3
Anthra then Trastu AC x 4 , then Trastu + Taxane
ICC NYHA
Grade 3 - 4
Control arm
BCIRG 006 FinHER HERA N-‐9831 BCIRG 006 N-‐9831 B31
3.5 4.1
2.5
1.6
0.6
0
0.4
0-‐0.8
0
1
2
3
4
256 paAents StraAficaAon
N+/N-‐
LVEF > 50%
Good safety profil, no grade 3/4 toxicity, except grade IV neutropeny
But stop treatment for 9 paAents due to FEV decrease
HercepAn 12 months 6 mg/kg /3 w
/ 3 w. 4 cycles
J1 J8 J15
75mg/m2
600mg/m2
HercepAn
C
T
Cycle 1, J1 ➔ 4 mg/kg 90 min, then 2 mg/kg/w
C
T
C
T
C
T
Jones SE et al. SABCS 2008, poster 2111
Phase II – docétaxel cyclophosphamide trastuzumab
Summary (1)
The risk of recurrence of breast cancer HER2 + for small tumors without lymph node involvement is
• 9-‐23 % at 5 years • about 2.5 @mes greater than in disease-‐HER2 nega@ve
Summary (2)
• Her 2 predictor of efficacy of trastuzumab? The answer is YES
• Receptor status and size, weigh@ng factor of decision? Probably NO
• It should probably take into account the risk-‐benefit ra@o and associated comorbidi@es in choosing treatment, but that does not prohibit an@ Her 2 treatment (and chemotherapy) for small tumors.
TN tumour
Preamble (valid for the remainder of the slides in forward and reverse)
No prospec@ve randomized clinical study reports the benefit of adjuvant chemotherapy for tumor size ≤ 10 mm and pN0 and whatever immunohistochemical subtype considered
About TN
• All tumors "triple nega@ve" does not correspond to the "basal-‐like" phenotype defined by the classifica@on of Peru and Sorlie
• « Basal Like » • SBR = high, low differen@a@on • High KI 67 • CK 5-‐6 + and CK-‐17+, EGFR +, BRCA1 + / -‐
• "Basal-‐like" between 58 and 67 years = 7% of breast tumors (1)
1. Sihto H, 2008, Clin Cancer Res
Associations of different TNBC subtypes.
Turner N C , and Reis-Filho J S Clin Cancer Res 2013;19:6380-6388
Click on image to magnify.
Basal-like 1: cell cycle, DNA repair and proliferation genes
Basal-like 2: Growth factor signaling (EGFR, MET, Wnt, IGF1R)
IM: immune cell processes (medullary breast cancer)
M: Cell motility and differentiation, EMT processes
MSL: similar to M but growth factor signaling, low levels of proliferation genes (metaplastic cancers)
LAR: Androgen receptor and downstream genes, luminal features Lehmann et al JCI 2011
Summary of retrospec@ve series T1ab with more than 10% of TN
Author Year
Number of patients Follow-up Summary of data Multivariate analysis
Kaplan 2009
110 4,2 year 89 % TN X 6.6 risk of recurrence vs RH+ HER2-‐ ayer adjustemnt on size, age et adjuvant chemotherapy (Y or N)
Curigliano 2009
95 60 months 5 events, 0 M+ Her 2+
Kwon 2012
56 pt1ab
61 months
DFS-‐5 years 92.5% Only one metasta@c recurrence for a TN
Age <35 and TN are the only two parameters impacting DFS (HR= 4.91 et 4.96) no Her 2
Park (issue de Kwon) 2011
Only 33 TN
61 months
OS-5 years= 90 %
Ho 2012
Only 194 TN, with Tmic 113 adjuvant chemotherapy Often CMF
73 months DFS-‐5 years = 95% 11 metasta@c recurrence
Come-‐back to consensus Size T1a T1b
Her 2+ RH - Her 2+ RH +
Luminal A Luminal B TN Her 2+ RH -
Her 2+ RH +
Luminal A
Luminal B
TN
NCCN 2014 No tt * HT*
HT *
HT * No tt * TZ + CT HT TZ+CT
HT CT according to Oncotype Dx
HT CT according to Oncotype Dx
CT
Saint Gallen 2011
No tt HT HT HT CT TZ + CT HT TZ + CT
HT CT according to Oncotype Dx and UPA/P1
HT CT according to Oncotype Dx and UPA/P1
CT
French Consensus Penault Llorca 2011
TZ + CT HT TZ + CT according to age, KI67, MI,grade embols
No tt TZ +CT HT TZ + CT according to age, KI67, MI,grade embols
CT
INCA 2012 No answer No answer No answer No answer
In summary (1)
• Global trend to provide chemotherapy for small TN but s@ll no consensus for T1a
• Given the narrowness of the benefit of chemotherapy for T1ab, it should take the following precau@ons • Consider any TN pT1ab low grade as suspect of not being a "basal-‐
like » • Do not hesitate to ask a second look on histology • Repeat IHC HER2 and HR • Repeat evalua@on of SBR and growth factors
• Remove histological subtype from TN known as good prognosis : adenoid cys@c carcinoma, androgene receptor +, apocrine
In summary (2) • Rela@ve benefit of chemotherapy with taxanes and anthracyclines,
whatever the size and histologic subtype, is about 30% according to the Oxford meta-‐analysis updated in 2012
• However, absolute benefit is depend on the risk of relapse, and the risk-‐benefit
• It seems reasonable to give chemotherapy only for following profiles • pT1B • No major comorbidi@es • Grade 3, high prolifera@on index
• Regimen of chemotherapy will be dictated according to the bibliography (3 FEC 100-‐3 Doce etc…) or according to personal convic@on (4 TC, pla@num compounds)
Luminal subtype
Retrospec@ve data from NSABP 2001 J Natl Cancer Inst 1024 pa@ents pT1ab HR + Tam vs CT-‐TAM
< 50 y, HR -‐ HzR = 0,61
Benefit : 13%
0,39 x 38.8
DFS-‐8 years = trend for CT-‐TAM vs TAM alone Impac@ng parameters in mul@variate analysis Age (cut-‐off = 50 years) Size (1 cm vs < 1 cm)
< 50 y, N-‐, HR +
HzR = 0,64
Benefit : 10%
0,36 x 27.4
Oxford meta-‐analysis 2011
Prognosis approach does not allow a predic@ve vision
• But, « honestly », chemotherapy may respond to laws of predictability, according to mechanisms of ac@on ? In absence of randomized prospec@ve study answering to our ques@on, is there a path to solve the problem..
L’approche de la sta@s@que modélisée Adjuvant Online
• Un site web qui permet d’évaluer le pronostic individuel • SG et SSR à 10 ans
• Utilise le suivi des patientes traitées entre 1988 et 1992 et enregistrées sur le « Surveillance Epidemiology and End-Results Registry » (SEER).
• 10% des patientes USA traitées sur cette période • Patientes de 36 à 59 ans avec enregistrement de la taille et du grade tumoral, du
statut hormonal et de l’atteinte ganglionnaire axillaire.
• Evaluation statistique du bénéfice individuel des traitements médicamenteux adjuvants
• Utilisation du bénéfice constaté de l’HT et de la CT adjuvante par la Méta-analyse de l‘Early Breast Cancer Trialists’ Collaborative Group • TAM, CMF, AC, TT séquentiel avec Taxanes
• Utilisation du bénéfice constaté des traitements adjuvants modernes dans les études adjuvantes randomisées récentes • Taxanes, IA
AOL : unperfectly approach
• No suitable for particular histology
• Tubular, papillar, mucinous, medullary
• No suitable for lobular
• No suitable for T1ab N-
• Under-estimation for efficacy of hormonotherapy
• AOL! Ignores the prognosis value of: • Ki67, Mito@c Index
• HER2 • PR and Quan@ta@ve expression of ER
Je vous propose une simula@on d’AOL !
• On par@ra du concept de Saint Paul : un gain addi@onnel de 5 % pour la récidive à 10 ans en plus de l’hormonothérapie
• On fera varier les paramètres d'âge et de grade histologique, par tranche d’âge de 5 ans
• On fera 3 simula@ons différentes basées sur l’état général
• On re@endra comme conven@on • Chimiothérapie : 3 FEC 100 – 3 TXT • Hormonothérapie : TAM jusqu’à 45 ans, traitement séquen@el à 50 ans, traitement par IA exclusif au delà
Addi@onal benefit of chemotherapy over 10 years in risk of recurrence in addi@on to hormone therapy, according to age and histologic grade for a T1ab tumor with Adjuvant OnLine!
Age 30 y. TAM
35 y. TAM
40 y. TAM
45 y. TAM
50 y. TAM-IA
55 y. IA
60 y. IA
65 y. IA
70 y. IA
Grade 1 7,7 5,2 5,3 5,3 3,4 3,3 2,7 2,8 2,5
Grade 2 9,1 6,3 6,3 6,3 4 4 3,3 3,3 3,1
Grade 3 10,6 7,3 7,4 7,4 4,7 4,7 3,8 3,9 3,6
Good health, IK 100 %
Age 30 y. TAM
35 y. TAM
40 y. TAM
45 y. TAM
50 y. TAM-IA
55 y. IA
60 y. IA
65 y. IA
70 y. IA
Grade 1 7,7 5,3 5,2 5,1 3,2 2,7 2,7 2,5 2,2
Grade 2 9,1 6,2 6,2 6,1 3,8 3,1 3,1 3 3,7
Grade 3 10,6 7,3 7,4 7,3 4,6 4,6 3,7 3,5 3,2
Evolu@onnary Health state, depending on the age
Age 30 y. TAM
35 y. TAM
40 y. TAM
45 y. TAM
50 y. TAM-IA
55 y. IA
60 y. IA
65 y. IA
70 y. IA
Grade 1 7,5 4,9 4,9 4,5 2,2 2,3 1,4 0,7 0,4
Grade 2 8,9 6 5,7 5,5 3,1 2,8 1,7 1 0,4
Grade 3 10,3 7 6,6 6,4 3,7 3,2 1,9 1 0,4
Poor general condi@on, 2 significant comorbidi@es
Other approaches, other perspec@ves…
• More personalized sta@s@cal approach: "No�ngham Prognos@c Index" taking into account the expression of HR and Her2 Oncotype Dx
• Hormone therapy signatures • UPA/P1
Oncotype DX®
16 cancer genes and 5 referent genes from three study
60
Paik et al. N Engl J Med. 2004;351:2817-2826.
Catégorie SR (0-100) Low risk RS < 18 Intermediate risk 18 < RS < 31 High risk RS ≥ 31
PROLIFERATION Ki-67
STK15 Survivin
Cyclin B1 MYBL2
OESTROGENES ER PR
Bcl2 SCUBE2
INVASION Stromelysine 3 Cathepsine L2
HER2 GRB7 HER2
REFERENCE Beta-actine
GAPDH RPLPO
GUS TFRC
GSTM1 BAG1
CD68
RS =
+ 0.47 x HER2 Group Score - 0.34 x ER Group Score + 1.04 x Proliferation Group Score + 0.10 x Invasion Group Score + 0.05 x CD68 - 0.08 x GSTM1 - 0.07 x BAG1
Oncotype DX® Validation Clinique: RS used as a continuous prognostic factor
• The recurrence score predicts the likelihood of beneficial effects of chemotherapy and the risk of recurrence at 10 years
61
Paik et al. N Engl J Med. 2004;351:2817-2826.
My SR is 30. What is the risk of recurrence in 10 years?
NSABP B-20: Many Small Tumors Have Intermediate to High Recurrence Score® Disease
Paik S, et al. J Clin Oncol. 2006;24:3726-3734.
33%
20% 19% 23% 21%
46%
N = 110 N = 318 N = 196 N = 24
Rec
urre
nce
Scor
e
≤1 cm 1.1-2 cm 2.1-4 cm >4 cm
Clinical tumor size
0
20
40
60
80
100 P=0.001
64% 56% 46%
16% 25% 30%
WSG-‐Plan B study (n=2551 )
Gluz O, et al. SABCS 2011 63
Risque intermédiaire risk (18-30)
Risque élevé (≥31)
Risque faible (<18)
Ki-67 <14 Ki-67 ≥14 Central grade
3%
36%
61%
19%
43%
38%
37%
63%
5%
39%
56%
30%
39%
31%
uPA/PAI-1 1 2 3 low high