Transcript HER2

Comparison between Pathologic
Characteristics of Her2 Negative
and Positive Breast Cancer in a
Single Cancer Center in Jordan
DR MAJDI A. AL SOUDI, MD, FACS
BREAST SURGEON, KHH BREAST UNIT
ROYAL MEDICAL SERVICES
Background
•Human
epidermal growth factor 2(Her2) is a
protein found in breast cancer cells. It is thought to
have an impact on cell growth.
•Her2
status is a prognostic factor and is important
in planning for the treatment of patients with Her2
positive breast cancer.
Relationship between
Her2 and other breast
cancer tumor markers
•Vascular
•VEGF
endothelial growth factor (VEGF)
is responsible for tumor angiogenesis
A 2004 study of 611 patients with primary breast cancer showed a significant correlation
between overexpression of HER2 and 2 VEGF isoforms (P<0.001)
•
•The
aggressive phenotype of HER2-overexpressing tumors may be due in part to VEGF
•Estrogen
(ER) and progesterone receptors (PR)
•In
a study by Seshadri et al (N=1056), HER2 overexpression was significantly associated
with negative ER and PR status (P<0.00001 and P<0.0006, respectively)
•Hormones
such as estrogen and progesterone may suppress HER2 expression, so that
hormone-receptor–positive tumors are less likely to be HER2-positive .
•This
interaction may explain why many HER2-positive tumors are unresponsive to
hormone therapy
HER2 is a negative prognostic
factor
•A
landmark study by Slamon et al (N=189) showed a highly statistically
significant correlation between HER2 gene amplification and shorter time
to disease relapse (P<0.0001) as well as shorter overall survival (P=0.0011)
•In
a study of patients with stage I-III disease (N=1056), 3-fold or greater
gene amplification of HER2 was associated with significantly shorter
disease-free survival (risk ratio=1.95, P=0.0027)
•HER2
gene amplification was also significantly associated with
pathologic stage at diagnosis, axillary node involvement, and histologic
subtype
•In
an additional study of 580 node-negative patients, HER2
overexpression was associated with higher risk of disease recurrence (risk
ratio=2.36, P=0.002)
Objective
•Her2
positive and Her2 Negative BC comparison regarding:
•Estrogen receptor(ER) and Progesteron receptor(PR) status,
•adverse prognostic factors such as lymphovascular
involvement(LVI) and perineural involvement(PNI),
•lymphnode involvement,
•tumor histological grade
•tumor size,
•tumor histological type
Materials and Methods
•A
retrospective study conducted in Al-Hussein Hospital in
Amman from Jan 2009 till Jan 2013.
•This
study revised the post operative histopathology reports of
three hundred and sixty eight breast cancer cases. They were
divided into Her2 negative and Her2 positive receptor status.
•The
factors that were compared were ER and PR status,
adverse prognostic factors (LVI and PNI), lymphnode
involvement, tumor histological grade, tumor size and tumor
histological type in women with Her2 negative and her2
positive breast cancer.
Distribution Regarding Her2 Status
Total no of cases: 368
80, 22%
her2 her 2 +
288, 78%
Estrogen Receptor Status
250
200
ER+
Er-
150
100
50
0
her2-
Her2+
ER+ %
ER- %
Her2-
79.2%
20.8%
Her2+
56.25%
43.75%
P Value: < 0.0001
Progesteron Receptor Status
250
200
Pr+
PR-
150
100
50
0
her2-
Her2+
PR+ %
PR- %
Her2-
74%
26%
Her2+
48.75%
51.25%
P Value: < 0.0001
LVI and PNI Status
250
200
LVI+
LVIPNI+
PNI-
150
100
50
0
her2-
Her2+
LVI+ %
LVI- %
PNI+ %
PNI - %
Her2-
50.35%
49.65%
25%
75%
Her2+
65%
35%
22.5%
77.5%
P Value: 0.0226
P Value: 0.7689
LN Status
100
80
0 LN
LN 1-3
LN 4-9
LN >9
60
40
20
0
her2-
Her2+
Her2-
Her2+
0 LN %
26.74 %
31.25 %
1-3 LN %
25 %
25 %
0 LN %
26.74% 31.25%
4-9 LN %
22.22 %
26.25 %
LN+ %
73.26% 68.75%
>9 LN %
18.75 %
17.5 %
Her2-
Her2+
P Value: 0.4803
Tumor Grade Distribution
200
150
G1
G2
G3
100
50
0
her2-
Her2+
Her2-
Her2+
G1 %
8.3%
3.75%
G2 %
56.94%
40%
G3 %
34.72%
56.25%
Tumor Size
200
150
T1 <2cm
T2 2-5 cm
T3 >5 cm
100
50
0
her2-
Her2+
Her2-
Her2+
T1 <=2cm %
19.44 %
15 %
T2 2-5cm %
61.46 %
57.5 %
T3 >5 cm %
19.1 %
27.5 %
Tumor Type Distribution
250
200
IDC
ILC
other
150
100
50
0
her2-
Her2+
Her2-
Her2+
IDC %
92.5 %
82.99 %
ILC %
5%
14.24 %
2.5 %
2.77 %
OTHER %
Summary
Her2 -ve
Her2 +ve

74% ER, PR positive

50% had ER, PR +ve

50.3% negative LVI

65% LVI positive

75% negative PNI

22% PNI positive

26.7% had no axillary LN
involvement, 32.2% had 1-3
LN

68.8% had axillary LN
involvement.

53.8% had grade 3 followed
by grade 2 40%.

57.5% had T2 tumors
followed by T3 tumors
in27.5%

56.9% had Grade 2 tumor

61.5% had tumor size
between 2 and 5 cm (T2).
Crosstalk between ER and
Her2 Pathways
•The
biological effects of estrogens on breast cancer cells are mediated
through two nuclear receptors known as ER and ER β
•The
binding of estrogen to ER induces phosphorylation of the receptor,
triggering receptor dimerization and recruitment of coregulatory
proteins, and facilitating the binding of the receptor to promoter regions
of DNA and transcription
•Estrogen
induces the expression of genes that encode proteins
important for tumor growth, such as the insulin-like growth factor I
receptor (IGF-IR), cyclin D1, collagenase, insulin growth factor II (IGF-II),
and VEGF
•Genes
downregulated by estrogens include the EGFR and HER2
Conclusion

Her2 negative tumors are associated with other
favorable characteristics as ER, PR+ve, relative
small sized tumors, moderate histological grade,
and mostly limited number of involved LN

Her2 positive tumors are more aggressive, more
Lymphnode involvement, Er,Pr 50% -ve, positive
LVI, less differentiated tumors, larger tumor size all
in favour of a worse prognosis.
Thank you