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10 2010

JOURNAL OF CLINICAL ONCOLOGY



Hagen Kennecke, Rinat Yerushalmi, Ryan Woods, Maggie Chon U. Cheang, David Voduc,
Caroline H. Speers, Torsten O. Nielsen, Karen Gelmon
British Columbia Cancer Agency; Genetic
Pathology Evaluation Centre, University
of British Columbia, Vancouver, British
Columbia, Canada; and the Lineberger
Comprehensive Cancer Center, University
of North Carolina at Chapel Hill, Chapel
Hill, NC.
2 2009 .;
8 2010 .;
24 2010 . :
www.jco.org.
Canadian
Breast Cancer Foundation, British Colubia-Yukon Division. Genetic
Pathology Evaluation Centre

sanofi-aventis (),
Michael Smith Foundation for
Health Research.


.

Hagen Kennecke, MD,
MHA, FRCPC, Vancouver Clinic, Division
of Medical Oncology, British Columbia
Cancer Agency, 600 West 10th Ave,
Vancouver, British Columbia, V5Z 4E6,
Canada; e-mail: hkennecke@bccancer.
bc.ca.
2010 by American Society of Clinical
Oncology

()
; , , .

, 19861992 .,
.
: , , 2 (HER2-), HER2, , . : , , ,
, , / . .
, .

3726 14,8 .
2,2 ( ), 1,6 ( ), 1,3 ( HER2+), 0,7 (HER2+) 0,5 () (p < 0,001). ,
, . ,
, HER2+, HER2+ , .
, , .
, .

0732-183X/10/2820-3271/$20.00

DOI: 10.1200/JCO.2009.25.9820

.
J Clin Oncol 28:3271-3277. 2010 by American Society of Clinical Oncology

,
2030 % ()
.1 .

, ,
,
, 2 2
(HER2).3 .

() (-), -

, , ,
, 4 -.5 .6
,
. , ,7-12
HER2
.2,13-22


,23 24,25 .26-28

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271

Kennecke et al.

Agency, . Estrogen
Receptor Tissue Bank 4543 ; 146 (3,2 %) - (1). 671
(0) -
. 3726 .

( ).29,30 ( -
) (), (), HER2,
Ki-67, (EGFR) () 5/6.26,28 - -
(, 1 %), HER2 3+; 2+
in situ ( 2,0).
, 50 , .

, .


, .
15-

: , , HER2+, HER2+ ; - ,
.

, 19861992 ., British Columbia Cancer

1. 3726

A (n = 1639)

a
T02
T34

Na
N0
N1
N2N3

62
5171

B (n = 893)
.

60
4770

HER2+ (n = 243)
.

58
4868

HER2+
(n = 266)
.

(n = 367)

56
4665

53
4265

(n = 318)
.

56
4567

< 0,001

379
43

23,1
2,6

284
27

31,8
3,0

73
11

30,0
4,5

92
4

34,6
1,5

148
13

40,3
3,5

104
11

32,7
3,5

< 0,001

1416
66
157

86,4
4,0
9,6

741
45
107

83,0
5,0
12,0

196
20
27

80,7
8,2
11,1

214
21
31

80,5
7,9
11,7

299
22
46

81,5
6,0
12,5

251
25
42

78,9
7,9
13,2

0,0019

909
631
19

55,5
38,5
1,2

446
375
24

49,9
42,0
2,7

102
120
9

42,0
49,4
3,7

114
129
5

42,9
48,5
1,9

218
123
4

59,4
33,5
1,1

179
115
8

56,3
36,2
2,5

< 0,001

80

4,9

48

5,4

12

4,9

18

6,8

22

6,0

16

5,0

618
86

37,7
5,2

440
46

49,3
5,2

146
6

60,1
2,5

141
8

53,0
3,0

147
20

40,1
5,4

128
17

40,3
5,3

< 0,001

970
549
120

59,2
33,5
7,3

364
490
39

40,8
54,9
4,4

71
162
10

29,2
66,7
4,1

56
203
7

21,1
76,3
2,6

41
317
9

11,2
86,4
2,5

100
199
19

31,4
62,6
6,0

< 0,001

1489
150

90,8
9,2

826
67

92,5
7,5

237
6

97,5
2,5

259
7

97,4
2,6

334
33

91,0
9,0

274
44

86,2
13,8

< 0,001

243
1190
206
922

14,8
72,6
12,6
56,3

132
651
110
566

14,8
72,9
12,3
63,4

51
169
23
162

21,0
69,5
9,5
66,7

42
195
29
116

15,8
73,3
10,9
43,6

44
267
56
118

12,0
72,8
15,3
32,2

47
231
40
143

14,8
72,6
12,6
45,0

0,1699

< 0,001

392

23,9

329

36,8

104

42,8

142

53,4

176

48,0

129

40,6

< 0,001

25
888
726

1,5
54,2
44,3

14
510
369

1,6
57,1
41,3

2
160
81

0,8
65,8
33,3

3
162
101

1,1
60,9
38,0

7
200
160

1,9
54,5
43,6

6
173
139

1,9
54,4
43,7


12
3

/






b

, c

95%
10- , %c
95%

2,2
1,92,5
70
67,872,3

1,6
1,41,8
54,4
51,257,7

1,3
1,11,7
46,1
39,852,4

0,7
0,60,8
48,1
42,154,1

0,5
0,40,7
52,6
47,557,7

0,9
0,71,1
62,6
57,367,9

0,0127

< 0,001

< 0,001

. 2; .
: ; ; .
a
American Joint Committee on Cancer, 6- , 2002.
b
, , ; .
c
- .
272

JOURNAL OF CLINICAL ONCOLOGY


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Copyright 2010 American Society of Clinical Oncology. All rights reserved.

3726 , 44 % , 24 % , 6,5 %
HER2+, 7,1 % HER2+, 9,8 % 8,5 % .
14,8 . , . 1.
,
HER2+ (p < 0,001). 4259 %
,
(59 %). (
) 3- , www.jco.org

(86,4 %). 56, 63


67 % , HER2+ ; 1/3 -
.
48, 41, 43 53 % , , HER2+ HER2+ .


10-
(p < 0,001): 70 % , 54,4 % , 46,1 %
HER2+, 48,1 % HER2+, 52,6 % 62,6 % .
:
2,2 , 1,6 ,
HER2+ 1,3 , HER2+ 0,7 ,
0,5 0,9 (p < 0,001).
15 :
27,8 %, 42,9 %,
HER2+ 47,9 %, HER2+ 51,4 %,
43,1 % 35,1 %. . 1 .
: , HER2+ 5 .
( . . HER2+)
515 . 15
(. . 1).


15- . 2.
.
(2,2 %) (4,7 %) .
HER2+ HER2+ ,
, . -

; : http://www.gpecimage.ubc.ca/tma/web/viewer.php; username: luminalB; password: luminalb.


( ).26-28 : (+ / + Ki-67 < 14 %), (+ /
+ Ki-67 14 %), HER2- (+
/ + HER2+), HER2- ( , HER2+)
(, , HER2, EGFR+ / 5/6+).
()
EGFR 5/6 .
Breast Cancer Outcomes Unit Database,
, , , ( ), . ,
. : (
, , , ),
, ( ), (
), (
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( , , ), (
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, , ) ( , ).
2 .

.

. , , ,31

. .31 ;
- . 2. ; ( ) ,

. SAS ( 9.1.3, SAS Institute, ) R
Statistical Language ( 2.9.0; http://cran.r-project.org/). Research Ethics Board British Columbia
Cancer Agency.

1,0
0,8
0,6

A
B
HER2+
HER2+

0,4
0,2
p<0,001

10

15

,
. 1.

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Copyright 2010 American Society of Clinical Oncology. All rights reserved.

273

Kennecke et al.

2. 15-

,
%

95% ,
%

1639

2,2

1,63,0

7,9

6,79,4

6,7

5,57,9

18,7

16,820,7

4,5

3,55,6

7,8

6,69,2

3,8

2,94,8

893

4,7

3,46,2

13,8

11,616,2

13,4

11,215,8

30,4

27,433,5

9,6

7,811,7

14,7

12,517,2

8,1

6,410,0

HER2+, +, +

244

7,9

4,812,0

21,3

16,326,7

17,7

13,222,8

30,9

25,236,7

10,5

7,014,8

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6,6

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HER2+, ,

266

14,3

10,418,8

23,3

18,428,6

24,1

19,129,3

30,1

24,735,7

13,0

9,217,4

16,2

12,020,9

8,8

5,812,7

367

10,9

8,014,3

9,3

6,612,5

18,5

14,722,7

16,6

13,020,6

17,2

13,521,2

12,8

9,616,5

10,4

7,513,7

318

7,2

4,710,4

10,7

7,614,4

12,5

9,116,5

15,1

11,419,4

12,3

8,916,1

9,2

6,312,7

9,2

< 0,001

< 0,001

,
%

< 0,001

95% , , 95% ,
%
%
%

< 0,001

,
%

< 0,001

95% ,
%

, 95% , , 95% ,
%
%
%
%

< 0,001

,
%

95% ,
%

6,212,9
< 0,001

. p , .

, , 10,9, 18,5, 16,6 17,2 % 9,3 %.



, (. 3).
HER2+ (28,7 %), (25,2 %) (22 %) ,
HER2+ (15,4 %) . (p < 0,001).
(66,6 %), (71,4 %) HER2+ (65 %) , (39 %).
-
(. 4). , ,
. , , N , .
, , (- / ),
, , .
, ( [] 0,5; 95%-
[95% ] 0,40,8) (
0,6; 95% 0,50,8). HER2+ ,
. ( 3,7; 95% 2,1
6,5), ( 2,5; 95% 1,63,8) ( 2,8; 95% 1,84,5),
( 0,5; 95% 0,30,8) ( 0,4; 95%
0,20,6). , .

,
- / ,

, HER2+, ( 0,6; 95% 0,40,9)
( 1,8; 95% 1,03,0; .
. 1 , ).

,
. ,
.
, - .
, .
,
;
. , 5667 %
; . 1,32
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,
, ,

3.

458

35

7,6

131

28,6

109

23,8

305

66,6

73

15,9

129

28,2

62

13,5

36

7,9

378

41

10,8

121

32,0

115

30,4

270

71,4

88

23,3

133

35,2

73

19,3

13

3,4

HER2+, +, +

117

18

15,4

52

44,4

43

36,8

76

65,0

26

22,2

40

34,2

16

13,7

5,1

HER2+, ,

136

39

28,7

62

45,6

64

47,1

81

59,6

34

25,0

43

31,6

23

16,9

4,4

159

40

25,2

34

21,4

68

42,8

62

39,0

63

39,6

47

29,6

38

23,9

11

6,9

109

24

22,0

35

32,1

39

35,8

47

43,1

39

35,8

31

28,4

28

25,7

5,5

< 0,001

< 0,001

< 0,001

< 0,001

< 0,001

0,3214

0,0056

0,1338

. p 2.
274

JOURNAL OF CLINICAL ONCOLOGY


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Copyright 2010 American Society of Clinical Oncology. All rights reserved.

4.

95%

95%

95%

95%

95%

95%

95%

A ()

1,4

0,82,3

1,1

0,81,5

1,4

1,01,9

1,2

0,91,7

1,4

0,92,0

1,3

0,91,8

1,3

0,81,9

HER2+, +, +

2,1

1,14,1

2,3

1,43,7

2,0

1,33,3

0,9

0,61,5

1,1

0,61,9

1,3

0,82,0

0,8

0,41,5

HER2+, ,

5,3

3,09,2

1,7

1,12,6

3,2

2,15,0

0,9

0,61,3

1,5

0,92,5

1,1

0,71,7

1,1

0,62,0

3,6

2,16,4

0,5

0,30,9

2,5

1,63,9

0,4

0,20,6

2,9

1,84,5

1,0

0,61,6

2,0

1,23,3

3,6

1,96,9

1,0

0,61,7

2,1

1,33,5

0,4

0,20,6

2,9

1,74,9

0,9

0,51,5

1,8

1,03,2

T34

0,2

0,10,4

0,5

0,30,8

1,4

1,11,9

0,7

0,61,0

2,3

1,83,1

2,1

1,62,9

1,5

1,22,0

2,2

1,63,1

2,2

1,63,0

1,5

1,02,3

> 50

0,5

0,40,7

0,6

0,50,8

. N, , , . N
, . ,
. .
: ; .

. HER2+
.35 ,
.
,
.
.
;
-
.
,
,
.


, .
,36,37 ,
- , 5 .36,38
, HER2+ . HER2
, HER2+ , 5 , 15
HER2+ .
15 .
( , , HER2)
6 % .18,39,40 10,9 7,2 %
.
1016 % HER2+ ,41,42
14,3 %, , , HER2+ (7,9 %).
HER2+ 2534 %,13,15,43,44 28,7 % HER2+ ,
15,4 % HER2+ . www.jco.org


HER2+ + HER2+ 13 .
- .2,16,23
:
, . ,7,10
, , . EGFR, -2 1 2.
,
, .9
.
, , ,
.7,14 , 50
, , ,
. (34)
, . , ,4
,
,
. , , ,
, .
American Society of Clinical Oncology
, , .45-47 HER2+
(28,7 %), (25,2 %)
(22 %)
. , ,
HER2+ .

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275

Kennecke et al.

, HER2+
HER2+ 30 %, . ,

.48
. , :
.49
,
HER2+ HER2+
RANK. ,
, .50 ,
, ,27,28,51
.

, .
,
,
, , .

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276

: Hagen Kennecke, Rinat Yerushalmi,


Ryan Woods, Maggie Chon U. Cheang, Karen Gelmon
: Hagen Kennecke, Torsten O. Nielsen, Karen Gelmon
: Hagen Kennecke, Ryan
Woods, Caroline H. Speers
:
Ryan Woods, Maggie Chon U. Cheang, David Voduc, Caroline
H. Speers, Torsten O. Nielsen, Karen Gelmon
: Ryan Woods, Maggie Chon U.
Cheang, David Voduc, Caroline H. Speers, Torsten O. Nielsen,
Karen Gelmon
: Hagen Kennecke, Rinat
Yerushalmi, Ryan Woods, Maggie Chon U. Cheang, David Voduc, Caroline H. Speers, Torsten O. Nielsen, Karen Gelmon
: Hagen Kennecke, Rinat Yerushalmi,
Ryan Woods, Maggie Chon U. Cheang, David Voduc, Caroline
H. Speers, Torsten O. Nielsen, Karen Gelmon
: Hagen Kennecke, Rinat Yerushalmi, Ryan Woods, Maggie Chon U. Cheang, David
Voduc, Caroline H. Speers, Torsten O. Nielsen, Karen Gelmon

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