Is mammacarcinoom onder de veertig jaar morfologisch en genetisch een andere ziekte? Marc van de...
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Transcript of Is mammacarcinoom onder de veertig jaar morfologisch en genetisch een andere ziekte? Marc van de...
Is mammacarcinoom onder de veertig jaar morfologisch
en genetisch een andere ziekte?
Marc van de Vijver, Netherlands Cancer Institute, Amsterdam, NL
Age & local controlLocal recurrence risk for 1393 breast carcinomas treated with BCT according to different age groups
Elkhuizen et al. Int J Radiat Oncol Biol Phys 40: 859-867, 1998
Age
<35
35-44
45-54
55-64 65-74
75
LOCAL RECURRENCE RISK3
0
20
10
0
years
121086420
% e
ve
nt fr
ee
1,0
,9
,8
,7
,6
,5
,4
,3
,2
,1
0,0
> 40
<= 40
RR 1.37, P < 0.001
Overall survival adjusted for tumor size, nodal status, chemotherapy and trial
9500+ patients with primary operable breast cancer from 4 randomized EORTC trials
Differences between breast carcinoma in young patients compared to older patients
<40 years• 50% grade 3• 50% ER negative
> 60 years• 20% grade 3• 20% ER negative
There are also small differences in sizeand % of lymph node positive patients
Histopathological factors
common precursor?
LCIS
well diff DCIS
moder diff DCIS
poorly diff DCIS
?
E-cadherininactivation
LOH 16q
invasive lobular carcinoma
invasive ductal carc.grade 1
invasive ductal carc.grade 2
invasive ductal carc.grade 3
invasive ductal carc.grade 3
p53 mut., HER2 gene amplif.BRCA1/2germline mutation
inactivationof BRCA1/2 wildtypeallele
Differences between breast carcinoma in young patients compared to older patients
<40 years• 10% is BRCA1/2
associated
> 60 years• 2% is BRCA1/2
associated
No major differences in the type of genetic alterations in sporadic tumors
Genetic factors
Histologic grade
Control BRCA1 BRCA2
Grade 1 24% 9% 11%
Grade 2 40% 25% 48%
Grade 3 36% 66% 41%
Lakhani et al., J Clin Oncol 2003
Estrogen receptor in BRCA1 and 2 associated breast carcinomas
ER % cells positive
contr
BRCA1
BRCA2
<1 36%
90% 34%
1-50 11% 5% 8%
>50 52% 6% 54%
Lakhani et al., J Clin Oncol 2003
HER2 in BRCA1 and 2 associated breast carcinomas
HER2/neu control BRCA1 BRCA2
+ 15% 3% 3%
- 85% 97% 97%
Lakhani et al.JCO2003
P53 in BRCA1 and 2 associated breast carcinomas
P53(cut-off 50%)
control BRCA1 BRCA2
+ 22% 44% 39%
- 78% 56% 61%
Lakhani et al. JCO2003
Basal keratins in BRCA1 and 2 associated breast carcinomas
CK5/6 CK14
control BRCA1 BRCA2
+
14% 70% 23%
- 86% 30% 77%
Lakhani et al. (Breast Cancer Linkage Consortium) submitted
Scanned image of a flexjet25,000 gene human
microarray
Hybridized with mixture of ‘red’-labeled cRNA of a tumor sample and ‘green’-labeled reference cRNA
Analysis of gene expression in breast cancer
Subgroup analysisof the N4+ study
Juliane Hannemann, Marc van de Vijver
Harm van Tinteren, Sjoerd Rodenhuis
Conclusions:
• Breast carcinomas in young patients are more frequently of high histologic grade and ER negative;
• However, this only partly explains poor outcome in these patients, especially the high local recurrence rate after BCT
• BRCA1/2 associated tumors have distinct histological and genetic features, but only represent a small proportion of all tumors, even in young patients
• No specific genetic alterations have been found to be associated with tumors in young patients