Structure et physiologie du système lymphatique

Prévention du lymphœdème après
cancer
S. Vignes, Unité de Lymphologie,
Hôpital Cognacq Jay, Paris
Conflit d’intérêt:
aucun
Pourquoi une femme a un
lymphœdème après cancer du sein ?
• Curage axillaire : 15% vs 6-8%
pour le ganglion sentinelle
• Radiothérapie même ne
comprenant pas le creux axillaire
• Obésité lors du cancer du sein
(IMC > 30 kg/m2), risque ≈ 4
• Mais les conseils classiques de
prévention (TA, piqûres…) ?
DiSipio T et al. Lancet 2013;14:500
Ridner SH et al. Support Care Cancer 2011;19:853
Published in final edited form as:
NIH-PA Author Manuscript
Department ofBreast
Physical
and
Occupational
Massachusetts General Hospital, Boston,
Cancer Res
Treat.
2013 November ; Therapy,
142(1): . doi:10.1007/s10549-013-2715-7.
A
bstract Impact of Body Mass Index and Weight Fluctuation on
Lymphedema
Jammallo
et al.
Risk in Patients Treated for Breast Cancer
Background—Identifying risk factors for lymphedema in patients treated for breast cancer has
1, Cynthia L. Miller, B.S. 1, Marybeth Singer, M.S., A.N.P.-B.C.,
Lauren S. Jammallo,
B.S.given
become increasingly
important
the current lack of standardization surrounding diagnosis and
A.O.C.N., A.C.H.P.N.2, Nora K. Horick, M.S. 3, Melissa N. Skolny, M.S.H.A. 1, Michelle C.
5, and Alphonse
treatment. Specht,
ReportsM.D.
on4the
association
of M.P.H.,
body mass
index (BMI)
and weight
changeM.D.,
with
, Jean
O'Toole, P.T.,
C.L.T.-L.A.N.A.
G. Taghian,
Table
3
1
Ph.D.
lymphedema
risk are conflicting. We sought to examine the impact of pre-operative BMI and
1Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
Multivariate
resultschange
for association
of demographic
and treatment factors with risk of lymphedema
post-treatment
weight
on the incidence
of lymphedema.
2Cancer Center,
Tufts Medical Center, Boston, MA
development
(RVC≥10%).
NIH-PA Author Manuscript
Methods—From
2005-2011,
787 newly-diagnosed breast cancer patients underwent prospective
3Biostatistics
Center, Massachusetts General Hospital, Boston, MA
Variable
HR
Lower
CL
P-value
arm volume
measurements
with a Perometer pre- and post-operatively.
BMICLwasUpper
calculated
from
4Division
of Surgical Oncology, Massachusetts General Hospital, Boston, MA
same-day
weight
and height measurements. Lymphedema was defined
as1.98
a relative10.1
volume0.0003
ALND
(vs. SLNB)
4.47
5Department
of Physical and Occupational Therapy, Massachusetts General Hospital, Boston,
changeBMI≥30
(RVC)
≥10%. Univariate and multivariate Cox proportional
hazards
models
used
MA(vs.of
25−<30)
2.46
1.22
4.99 were0.012
to evaluate
the association between lymphedema risk and pre-operative
BMI,
weight
change,
and
BMI≥30 (vs. <25)
3.58
1.66
7.70
0.001
Abstract
other demographic and treatment factors.
RLNR (vs. breast/chest wall only/none)
2.67
1.25
5.70
0.011
Background—Identifying risk factors for lymphedema in patients treated for breast cancer has
Results—By
multivariate
a pre-operative
BMI
≥30 was
significantly
associated
with an
Cumulativebecome
absoluteincreasingly
fluctuationanalysis,
inimportant
weight from
pre-op
(1 lb/molack
change
in weight)
1.07
1.04diagnosis
1.11
<0.001
given
the current
of
standardization
surrounding
and
Reports on the
association of
body
mass index (BMI)BMI
and weight
change
with
increased
risk treatment.
oflymph
lymphedema
compared
tolymph
a pre-operative
<25
andRLNR
25-<30
(p = 0.001 and p
ALND axillary
node
dissection,
SLNB
sentinel
node
biopsy,
BMI
body
mass
index,
regional
lymphedema risk are conflicting. We sought to examine the impact of pre-operative BMI
and lymph node radiation
= 0.012, respectively).
Patients
withona the
pre-operative
BMI 25-<30 were not at an increased risk of
post-treatment
weight change
incidence of lymphedema.
lymphedema compared
to patients
a pre-operative
(p=underwent
0.409).prospective
Furthermore, large
Methods—From
2005-2011,with
787 newly-diagnosed
breastBMI<25
cancer patients
post-operativearm
fluctuations
in weight,
whether
they reflected
weightfrom
gain or loss (i.e.
volume measurements
with aregardless
Perometer pre-of
and
post-operatively.
BMI was calculated
same-day weight
and height measurements.
was defined
as a relative
10 pounds gained/lost
per month),
resulted in Lymphedema
a significantly
increased
riskvolume
of lymphedema (HR:
change (RVC) of ≥10%. Univariate and multivariate Cox proportional hazards models were used
1.97, p = <0.0001).
pounds
≈ lymphedema
4.5 kg risk and pre-operative BMI, weight change, and
to evaluate 10
the association
between
other demographic and treatment factors.
Conclusions—Pre-operative BMI of ≥30 is an independent risk factor for lymphedema, whereas
Pag
Peut-on prévenir le lymphœdème ?
• Ganglion sentinelle
– diminuer la fréquence du
lymphœdème : 2,5-8%
– recherche du ganglion sentinelle
du bras (« sentibras »)
éviter son ablation lors du curage
axillaire
diminuer ainsi le risque de
lymphœdème
• Injection de bleu patenté face
postérieure bras, 1er et 2ème espace
interdigital
• Repérage axillaire : éviter l’ablation de ce
ganglion (nég. même si curage +)
• Disparition complète de la coloration
bleue en 2 ans (50%), légère non gênante
(50%)
PLoS One 2016;11(2):e0150285
• Identification du ganglion sentinelle
du MS lors des curages: 83%
• LO : 4,1%
Microsurgery 2014;34:421-4
ALV « préventives » même temps chirurgical
que le traitement du cancer
Microsurgery 2014;34:421-4
Lymphœdème à 1 an : 4%
1. Etude prospective
(cohorte PAL : Physical Activity
Lymphedema)
2. Questionnaire sur 30 items (FDR
potentiels) à 3, 6 et 12 mois
3. LO défini > 5% (volumétrie à eau) à 3,
6 et 12 mois
1955
1962
1998
2006
2009
2010
2005
Ann Surg 2015
• Reconstruction mammaire immédiate
(RMI) après mastectomie
• Suivi médian : 22 mois
• RMI :
– expandeur puis prothèse
– prothèse en un seul temps
– lambeau autologue (transverse rectus
abdominis myocutaneous : TRAM, deep inferior
epigastric artery perforator : DIEP).
Reconstruction mammaire immédiate
LO à 2 ans
• Global :10,5%
• RMI : 5,1%
• Sans reconstruction :
26,7%
• Prothèse : 4%
• Lambeaux
autologues : 9,9%
Reconstruction mammaire immédiate
• RMI: utile pour  risque LO après
traitement d’un cancer du sein
même cancer invasif
• Bénéfice RMI avec implants et non
lambeaux autologues
• Hypothèse « classique » : apport de
tissus sains pour améliorer la
circulation lymphatique, ischémie
locale par l’expandeur : favoriser la
néolymphangiogénèse…
• Importance de la détection précoce
d’un LO
– bio-impédancemétrie (courant de
faible intensité)
– mesure de la constante tissulaire
di-électrique (signal de 300 MHz)
– clinique par auto-diagnostic
(éducation du patient)
Conséquences
Prise en charge
précoce
• Jamais de DLM en
première intention
• Compression
élastique
• Voire bandages
peu élastiques :
réduction LO débutant
training group reportedPublication
pain moreoften
at threemonthsand
six monthscompared
toCastro-Sanchez
thecontrol group.
HRQoL
ported.
In
2011,Onestudy
Torres 2010reported
and Zimmermann
statusand
date: New, published
in Issue2,
2015.
Effects of interventions
2012 no explicit distinction wasmadeand reported numberswere
and found no significantReview
differencebetween
thegroups.
content assess
ed asup-to-date: 23 May 2013.
Conservative
interventions
for preventing
clinically
detectable
See: Summary of findings
for the main comparison
Early treated ascumulative
incidence.
Patient education,physiotherapy
monitoringand
eSarlyinte
rvefor
ntion
including
MLD
patients
at riskMR,
forin
secondary
Due towho
substantial
and statistical
heterogeneity
for
upper-limb
lymphoedema
patients
areclinical
at risk
of Bossuyt
Citation:
tuiver
MM,
ten
Tusscher
Agasi-Idenburg
CS,
LucasC,
Aaronson
NK,
PMM.both
Conservativein
upper limb lymphoedemaafter breast cancer treatment; Summary short-term (lessthan 6 months) and medium-term (more than 6
preventing
clinically
detectableupper-limb
lymphoedemain
patientswho
are atof risk
of developing
lymphoedema afte
One study investigated
the 2effects
a lymphoedema
comprehensive
outpatient
follow-up
programme,
patient
education,
developing
after
cancer
therapy
of findings
Early of
shoulder
mobilising exercises
compared
tobreast
months,
less
thanconsisting
24 months)
follow-up,
(I²
= 86%, P =exercise,
0.008;
therapy.
CochraneDatabas
eof
S
ys
te
maticRe
vie
ws2015,
Issue2.
Art.
No.:
CD009765.
DOI:
10.1002/14651858.CD00
delayed
shoulder
mobilising
exercisesfor
patient
surgically
treated
monitoring of lymphoedemasymptomsand early intervention
for lymphoedema,
education
alone.forLymphoedemainciand I² compared
= 84%, P <to0.001
respectively
RR; and I² = 84%,
(Review)
forthecomprehensiveoutpatient
breast cancer; Summary of findings
3 Progressive
resistance any
P =timepoint)
0.01 for thecompared
HR), no meta-analyses
performed.
The
dencewaslower in
follow-up
programme(at
to educationwere
alone(65
people).
exercisefor
patientsat
risk
for
secondary
upper
limblymphoedema
results
of
all
studies
comparing
physiotherapy
with
MLD
to
any
Copyright
© 2015
TheCochraneCollaboration.
Published
Wiley
& Sons,compared
Ltd.
Participantsin theoutpatient
follow-up
programmehad
asignificantly faster
recoveryby
of John
shoulder
abduction
totheeducation
after breast cancer treatment
other intervention aresummarized in a single forest plot without
alonegroup.
Stuiver MM, ten Tusscher MR, Agasi-Idenburg CS, LucasC,
Aaronson
BossuytAnalysis1.2;
PMM Figure4 (Analysis
totals(see:
Figure3 NK,
(Analysis1.1);
Authors’ conclusions
Manual lymph drainage (MLD)
1.3)), and anarrativesummary of theresultsisprovided below. A
summary
outcomes
of these studies is also provided
A B of
S the
T Rmain
AC
T
in
’Summary
of
findings
’
table1.
draw firm conclusions about theeffectivenessof interventionscontaining MLD.
Based on thecurrent available evidence, wecannot
Background
Theevidencedoesnot indicateahigher risk of lymphoedemawhen startingshoulder-mobilising exercisesearly after surgery compared
Figure
3.
Forest
plotlymphoedemacan
ofShoulder
comparison:
1 beadebilitating
Early
physiotherapy
MLD vs
no early
physiotherapy
or
e interventions
for preventing
detectable
to adelayed
start (i.e.clinically
seven
daysafter
surgery).
mobility
(that
is, laterallong-term
armincluding
movementsand
forward
flexion)
isbetter
in the
Breast
cancer-related
sequelaof
breast
cancer
treatment.
Several
studiesha
physiotherapy
without
MLD,
outcome:
1.1
T
ime
to
event
for
lymphoedema.
b lymphoedema
in patients
whotheeffectivenessof
are
at risk
of differentcompared
treatmenttostrategiesto
reducetherisk of breast
cancer-related lymphoedema.
short term
when starting
shoulder
exercisesearlier
later. Theevidencesuggeststhat
progressiveresistanceexercisetherapy
ng lymphoedema
after
breast
cancer
therapy
doesnot increasetherisk of developing lymphoedema, provided that symptomsareclosely monitored and adequately treated if they
Objectives
(Review)
occur.
To assesstheeffectsof conservative (non-surgical and non-pharmacological) interventions for preventing clinically-det
Given
the
degree
of
heterogeneity
encountered,
limitedcancer
precision,
and the risk of biasacross theincluded studies, theresultsof this
Tusscher MR, Agasi-Idenburg CS, LucasC, Aaronson
Bossuyt
PMM
limbNK,
lymphoedemaafter
breast
treatment.
review should beinterpreted with caution.
Search methods
WesearchedtheCochraneBreast Cancer Group’s(CBCG) SpecialisedRegister, CENTRAL, MEDLINE, EMBASE, CIN
Figure 4. theWorld
Forest plotHealth
of comparison:
1 Early
physiotherapy
including
MLD vsTrialsRegistry
no early physiotherapy
(WHO)
International
Clinical
Platformorin May 2013.
P L A I N L A N GPsycINFO,
U A G E and
S physiotherapy
UMMAR
Y Organization
without
MLD, outcome: 1.3 Lymphoedema - medium term follow up.
of included trialsand other systematic reviewsweresearched.
Conservative interventionsfor preventing clinically detectable upper-limb lymphoedema in patients who are at risk of developing
lymphoedema after breast
cancer therapy
(Review)
Selection
criteria
Copyright © 2015 The Cochrane Collaboration. Published by John W iley & Sons, Ltd.
2
Randomised controlled trialsthat reported lymphoedemaastheprimary outcomeand compared any conservativeinterve
no intervention or to another conservativeintervention.
Data collection and analysis
Threeauthorsindependently assessed therisk of biasand extracted data. Outcomemeasuresincluded lymphoedema, in
of motion
of theshoulder,
psychosocial
morbidity, level of and
functioning
activitiesof daily life(ADL), and healthThisisareprint
of aCochranereview,
preparedpain,
and maintained
by TheCochraneCollaboration
published in in
TheCochraneLibrary
2015, Issueof2 life(HRQoL). Wherepossible, meta-analyseswereperformed. Risk ratio (RRs) or hazard ratio (HRs) werereported fo
http://www.thecochranelibrary.com
outcomesor lymphoedemaincidence, and mean differences(MDs) for rangeof motion and patient-reported outcome
Et si le lymphœdème après
cancer du sein avait une
composante génétique ?
• Diagnostic de lymphœdème par
impédancemétrie
• 110 femmes avec LO, 297 sans LO
• Analyse en aveugle du polymorphisme
de différents gènes
Gènes étudiés
•
•
•
•
•
•
•
•
•
•
•
Angiopoeitin-2 (ANGPT2)
Elastin microfibril interfacer (EMI-LIN1)
FOXC2, PROX1, LYVE1
Hepatocyte growth factor (HGF), lymphocyte
cytosolic protein 2 (LCP2)
Hepatocyte growth factor receptor (MET)
Neuropilin-2 (NRP2)
ROR orphan receptor C (RORC)
SpSRY-box 17 (SOX17)
Protein tyrosine kinase (SYK)
Vascular cell adhesion molecule 1 (VCAM1)
Vascular endothelial growth factor-B
(VEGFB), -C (VEGFC), -D (VEGFD), receptor 2 (VEGFR2), -receptor 3 (VEGFR3)
81 vs 71%
44 vs 60%
75 vs 85%
Et gène FOXC2
61 vs 72%
• 120 femmes : 98 sans et 22 avec lymphœdème
(apparu 6-18 mois après la chirurgie)
• Etude polymorphisme de plusieurs gènes candidats
• Résultats : VEGFR3, VEGFR2 et RORC (Retinoic
acid receptor-related Orphan Receptor gamma) =>
organogénèse lymphoïde, lymphangiogénèse
Conclusion
1. Nouvelles pistes de prévention
– chirurgicales (RMI)
– préventives
2. Changements des conseils données
aux femmes après cancers du sein
(poids, activités physiques)
3. Dépistage précoce LO et compression
élastique en première intention
4. Prédisposition génétique…