Multizentrizität

Operatives Procedere bei
Multizentrizität:
Ist eine Ablatio immer erforderlich?
C. Schumacher
Brustzentrum
St. Elisabeth-Krankenhaus
Ziele der
Mammakarzinomtherapie
 Optimale lokale Kontrolle
(Einfluss auf das Gesamtüberleben: 4 Lokalrezidive
führen zu einem brustkrebsbedingten Todesfall)
 Optimale lokoregionäre Kontrolle
 Fernmetastasenfreiheit
Lokale Kontrolle
 Lokalrezidivrate
Ziel:
max. 1% pro Jahr, um den negativen Effekt auf das
Überleben zu limitieren
Aktuelle Daten:
ca. 2-3% Lokalrezidive nach 5 Jahren
 Wichtigste Einflussfaktoren:
Tumorbiologie, Tumormasse, positive Ränder, junges Alter,
nicht durchgeführte Strahlentherapie oder adjuvante medikamentöse Therapie
Multizentrizität?
Multizentrizität: Häufigkeit
 Inzidenz lt. Literatur: 6 – 75%
je nach Definition, Ein- oder Ausschluss von
In-situ-Läsionen, pathologischer Aufarbeitung
und bildgebender Diagnostik
Holland et al:
in > 60% der Mastekomiepräparate bei vermuteter
Unifokalität Detektion weiterer Läsionen,
43% > 2 cm entfernt)
klinische Relevanz???
 Zunehmende Inzidenz durch
Verbesserungen in der bildgebenden
Diagnostik
Houvenaeghel G et al, World Journal of Clinical Oncology
Diagnosestellung
Multifokalität / Multizentrizität
Sensitivity of MRI versus mammography for detecting foci of multifocal, multicentric breast cancer
in Fatty and dense breasts using the whole-breast pathologic examination as a gold standard.
Sardanelli F et al., Am J Roentgenol 2004
•
•
Mammographie:
Sensitivität 60-75 % und PPV 73 -78 % je nach Gewebedichte
MRT:
Sensitivität 80 - 81% und PPV 65-71% je nach Gewebedichte
Accuracy and surgical impact of magnetic resonance imaging in breast cancer staging: systematic
review and meta-analysis in detection of multifocal and multicentric cancer.
N Houssami
Metaanalyse von 19 Studien, n=2610: bei median 16 % der Patientinnen zusätzliche Läsionen
Increasing the diagnosis of multifocal primary breast cancer
by the use of bilateral whole-breast ultrasound.
Wilkinson LS et al., Clin Radiol 2005
BBUS increased the preoperative diagnosis of multiple tumours in women presenting with primary breast
cancer, resulting in a management change in 8% of cases.
MRT und Multizentrizität:
eigene Daten
No. of
patients (%)
No. of patients
with malignant
lesions (%)
Additional lesions
87 (41,6)
34 (16,3)
Additional lesions close to
the tumor
45 (21,5)
26 (12,4)
64 (30,6)
12 ( 5,7)
MRI – result
n = 209
(Influence on resection volume)
Additional lesions outside the
resection volume
Characteristics of Multifocal and
Multicentric Breast Cancers
Kanumuri P et al., Ann Surg Oncol. 2015
Of 1495 invasive cancers, 1231 (82.3 %) were UF, 169 (11.3 %) were MF,
and 95 (6.4 %) were MC cancers.
 MC but not MF cancers were associated with young age at diagnosis,
larger tumor size, lymphovascular invasion, and node positivity.
 MF but not MC tumors were more likely to be ER/PR+Her2+ tumors and
less likely to be triple-negative cancers compared with UF tumors.
 MF tumors were more likely to be infiltrating ductal carcinomas with an
extensive intraductal component, and MC tumors were more likely to be
infiltrating lobular carcinomas.
 Concordance of histology and receptor status between primary and
secondary foci was high and was similar for both MF and MC cancers.
 Multicentricity remained an independent predictor of lymph node positivity
on multivariate analysis.
Pathological Characteristics of Both Tumors
in Bifocal and Bicentric Breast Cancer.
Mosbah R et al., Anticancer Res 2015
A total of 205 patients were included.
 The same histological type in 182 patients (89%)
 The same grade in 178 of the cases (96.7% and 100% for grade 3
lesions).
 Excellent immunohistochemical concordance with correlation
coefficients of 0.98, 0.96 and 0.99 for ER, PR and Ki67, respectively.
(HER2) status was available for both tumors in 177 cases (86%), with
a perfect concordance.
 No differences in molecular sub-type between tumor foci.
Frage:
Ist eine Ablatio
immer erforderlich?
1. Welche Rolle spielt die Multizentrizität für die lokale
Sicherheit und das Gesamtüberleben?
2. Profitiert die Patientin von einer intensiveren
präoperativen Bildgebung mit einer erhöhten
Nachweisrate multizentrischer Tumorherde?
3. Kann das operative Vorgehen bei Multizentrizität
das Outcome beeinflussen?
Was sagen die
Leitlinien?
S3 – Leitlinie 2012
St. Gallen Konsens 2015
ESMO Clinical Practice Guidelines
for diagnosis, treatment and follow-up 2015
In some patients, mastectomy is still carried out due to: tumour size (relative to
breast size), tumour multicentricity, inability to achieve negative surgical margins
after multiple resections, prior radiation to the chest wall/breast or other
contraindications to RT, or patient choice
NCCN Clinical Practice Guidelines in Oncology
(NCCN Guidelines) Version 2.2016
Lumpectomy is contraindicated for patients who are pregnant and would
require radiation during pregnancy; have diffuse suspicious or malignantappearing microcalcifications on mammography; have widespread
disease that cannot be incorporated by local excision through a single
incision with a satisfactory cosmetic result; or have diffusely positive
pathologic margins
AGO-Leitlinie
Aktuelle Praxis
Multifocality and multicentricity in breast
cancer and survival outcomes
Lynch SP et al., Oncologist 2013
MD Anderson
database
1997 - 2010
n = 3924,
695 (17,7%) MF
247 ( 6,3%) MC
med. FU 51 mo
Erhebung in England
M. Dixon, Edinburgh, BC3-Konferenz 2013
Metaanalysis: Impact of MRI
on Initial Surgical Outcomes
Is the use if breast MRI
predictive of mastectomy?
Killelea et al, World J Surg Oncol 2013
Yale database 2004-2009
Aktuelle
Studienlage
1.
Welche Rolle spielt die
Multizentrizität für die
lokale Sicherheit und das
Gesamtübeleben?
Multifocality and multicentricity in
breast cancer and survival outcomes
Lynch SP et al., Oncologist 2013
MD Anderson
database
1997 - 2010
n = 3924,
695 (17,7%) MF
247 ( 6,3%) MC
med. FU 51 mo
Comparing the outcome between multicentric and
multifocal breast cancer: what is the impact on
survival, and is there a role for guideline-adherent
adjuvant therapy? A retrospective multicenter
cohort study of 8,935 patients.
Wolters R et al., Breast Cancer Res Treat 2013
After Adjustment on age, tumor size, grade, nodal status and adjuvant therapy
according to guidelines no difference between unifocal and MF / MC tumors:
MC tumors:
RFS 0,88, p = 0,35
OS 1,08, p = 0,54
MF tumors:
RFS 1,05, P = 0,597
OS 0,92, p = 0,28
Effect of multifocality and multicentricity
on outcome in early breast cancer:
A systematic review and meta-analysis.
Vera-Badillo FE et al, Breast Cancer Res Treat 2014
2.
Profitiert die Patientin von einer
intensiveren präoperativen
Bildgebung mit der
erhöhten Nachweisrate
multizentrischer Tumorherde?
Comparative effectiveness of MRI in breast
cancer (COMICE) trial:
a randomized controlled trial
Turnbull et al., The Lancet 2010
Relationship of breast magnetic resonance
imaging to outcome after breast-conserving
treatment with radiation for women
with early-stage invasive breast carcinoma or
ductal carcinoma in situ
Solin LJ et al, J Clin Oncol 2008
• Patients and methods:
n = 756 during 1992-2001
215 patients with MRI, 541 without MRI,
med. FU 4,6 y
• Results:
8-year local failure rate 3% vs 4% (p=0,51)
8-year overal survival rate 86% vs 87% (p=0,51)
Magnetic resonance imaging in the planning of initial
lumpectomy for invasive breast carcinoma: its effect
on ipsilateral breast tumor recurrence after breastconservation therapy.
Hwang N et al., Ann Surg Oncol. 2009
 MRI was performed before 127 (27%) lumpectomies, while 345 (73%)
patients did not have a preoperative breast MRI.
 At median follow-up of 54 months (range 4.8-111.6 months), there was no
significant difference in actuarial 8-year IBTR rates between women with
preoperative MRI evaluation and women without MRI (1.8% versus 2.5%,
respectively; P=0.67).
 MRI visualization of tumors prior to lumpectomy did not influence the
achievement of negative margins and was not associated with lower rates
of re-excision (MRI: 11.8% versus no-MRI: 13.3%; P=0.50
Effect of MRI
on Local Recurrence After BCT
3.
Kann das operative Vorgehen
bei Multizentrizität
das Outcome beeinflussen?
Lokalrezidivraten nach BET bei
Multifokalität / Multizentrizität:
retrospektive Studienergebnisse
Houvenaeghel G et al, World Journal of Clinical Oncology
Woods et al:
Lokalrezidivraten bei
Multifokalität / Multizentrizität
Woods et al:
Lokalrezidivraten bei
Multifokalität / Multizentrizität
Is breast-conserving therapy
a safe option for patients with
tumor multicentricity and multifocality?
Yerushalmi et al, 2012
Database Breast Cancer Agency Vancouver 1989-2005
n = 11983 BCT, 7771 mastectomies
(11683 unifocal tumors, 300 MC/MF tumors)
med. FU 7,9 years
BCT in MF / MC: 50-69 years, no EIC, smaller tumors
Cumulative incidence of local relapse by unifocal versus multicentric/multifocal
disease for breast concerving therapy cases
Is breast-conserving therapy
a safe option for patients with
tumor multicentricity and multifocality?
Yerushalmi et al, 2012
Database Breast Cancer Agency Vancouver 1989-2005
n = 11983 BCT, 7771 mastectomies
(11683 unifocal tumors, 300 MC/MF tumors)
med. FU 7,9 years
BCT in MF / MC: 50-69 years, no EIC, smaller tumors
Cumulative incidence of local relapse by unifocal versus multicentric/multifocal
disease for mastectomy cases
Multifocality and multicentricity in breast
cancer and survival outcomes
Lynch SP et al., Oncologist 2013
MD Anderson database
1997 – 2010, n = 3924,
med. FU 52 mo
Multifocality and multicentricity in breast
cancer and survival outcomes
Lynch SP et al., Oncologist 2013
MD Anderson database
1997 – 2010, n = 3924, med. FU 52 mo
BET
Mastektomie
Mastektomie + RX
Comparing the outcome between multicentric and
multifocal breast cancer: what is the impact on
survival, and is there a role for guideline-adherent
adjuvant therapy? A retrospective multicenter
cohort study of 8,935 patients.
Wolters R et al., Breast Cancer Res Treat 2013
RFS in patients treated according to guidelines
MF tumors: BCT + RT vs Mastectomy
HR 1,25, p= 0,284
MC tumors: BCT + RT vs Mastectomy
BCT + RT vs Mastectomy + PMRT
HR 1,19, p= 0,7
HR 1,23, p= 0,64
Preliminary results: double lumpectomies for
multicentric breast carcinoma.
Kapoor NS et al., Am Surg. 2012
 Seven patients underwent double lumpectomies for multicentric
carcinoma. Median age was 69 years (range, 61 to 80 years). In five
patients, MRI identified ipsilateral second malignancies.
 All patients had two foci of invasive carcinoma, all tumors expressed
estrogen receptor, and none showed HER-2 overexpression. Tumor sizes
ranged from 0.7 to 2.9 cm. All patients had sentinel lymph node biopsies
and none had nodal metastasis.
 Median follow-up was 26 months (range, 18 to 85 months). No patient
developed locoregional recurrence.
Zusammenfassung
Zusammenfassung 1
 Zunehmende Inzidenz der Diagnose Multizentrizität durch
Verbesserungen in der bildgebenden Diagnostik mit konsekutiver
Steigerung der Mastektomierate weltweit.
 Die Diagnose Multizentrizität ist lt. Datenlage kein unabhängiger
Prognosefaktor für die Lokalrezidivrate und das Gesamtüberleben.
 Eine intensivere präoperative Bildgebung insbesondere unter
Einschluss der MRT-Mammographie ist bisher ohne nachweisbaren
Effekt auf die Lokalrezidivrate und das Gesamtüberleben
Zusammenfassung 2
 Steigende Evidenz, dass die BET in ausgesuchten Fällen eine
onkologisch adäquate Therapie ist.
Voraussetzungen:
- multidisziplinäre Patientinnenselektion
- präoperative onkologische und ästhetische Planung
- freie Ränder
- zufriedenstellende kosmetische Rekonstruktion
- postoperative Strahlentherapie ( 2 Boostbestrahlungen?)
- adäquate adjuvante medikamentöse Therapie
 Fehlen eindeutiger aktueller Leitlinien für das Management
Vielen Dank für Ihre Aufmerksamkeit!