| A. Unselected primary breast carcinomas |
| Author |
PIK3CA Mutations |
Exon |
Method |
mutation positive &clinical variables |
| # Mutations/ #Cases Tested |
% |
9 |
20 |
Other# |
| Samuels [1] |
1/12 |
8.3 |
|
|
|
Sequence all exons |
|
| Bachman [59] |
9/41 |
22.0 |
1 |
6 |
2 |
Sequence exons 1, 9, 20 |
|
| Campbell [60] |
28/70 |
40.0 |
15 |
9 |
4 |
SSCP all exons & DHPLC exons 9, 20 |
No association with ER, grade, LN |
| Saal [54] |
79/292^ |
27.0 |
26 |
40 |
13 |
Sequence exons 1, 2, 4, 5, 7,9, 12, 13,18, 20 |
ER+ PR+
Her-2/neu+ |
| Wu [9] |
19/92 |
20.6 |
13 |
6 |
|
Sequence exon 1, 9, 20 (Frozen tissue) |
|
| Lee [51] |
26/78^ |
33.3 |
4 |
22 |
|
SSCP exons 9, 20 |
|
| Levine 2005 [96] |
13/72 |
18.1 |
9 |
4 |
|
Sequence exons 9, 20 (Frozen tissue) |
|
| Li [52] |
95/250^ |
38.0 |
40 |
47 |
8 |
SSCP exon 7, 9, 20 (Frozen tissue) |
ER+ PR+, size. Worse survival |
| Buttitta [61] |
46/180 |
25.6 |
23 |
23 |
|
SSCP all exons & direct sequence exons 9, 20 (Frozen tissue) |
Exon 9: lobular. No association with age, size, ER, PR, LN. |
| Liang [53] |
33/80^ |
41.2 |
11 |
22 |
|
Sequence exon 9, 20 |
Age, stage. No association with ER. |
| Maruyama [63] |
54/176 |
30.7 |
17 |
29 |
8 |
Sequence exons 1, 2, 4, 7, 9, 18, 20 (Frozen tissue) |
ER+, pAKT+
Favorable prognosis. |
| Perez-Tenorio [55] |
66/270^ |
24.4 |
30 |
36 |
|
SSCP exon 9, 20 (Frozen tissue) |
ER+ Her2-, small size |
| Wood [95] |
5/11 |
45.4 |
3 |
2 |
|
Full genome sequencing |
|
| Barbareschi [62] |
45/163 |
27.6 |
24 |
21 |
|
SSCP exon 9, 20 (Frozen tissue) |
Exon 20-improved overall and DF survival. Exon 9-worse overall and DF survival. |
| Benvenuti [97] |
14/86 |
16.3 |
6 |
8 |
|
Sequence exons 9, 20 |
No association with age, ER, LN |
| Lai [72] |
39/152 |
25.7 |
14 |
21 |
4 |
Sequence exons 7, 9, partial 4, 20 |
Exon 20 worse overall survival |
| Liedtke [98] |
23/140 |
16.4 |
12 |
11 |
|
Sequence exon 1, 9, 20 (Frozen FNA) |
Exon 9: LN-, ER+ |
| Stemke-Hale [56] |
117/547^ |
21.4 |
40 |
73 |
7 |
PCR-mass-spec (21 codons) (Frozen tissue) |
ER+ Her2+, less common in basal-like. No association with outcome in tamoxifen treated ER+. |
| Leong [99] |
6/20 |
30 |
3 |
3 |
|
Sequence exon 9, 20 |
Two H1047R mutations, others non-hotspot |
| Haverty [100] |
13/51 |
25.5 |
7 |
4 |
2 |
Sequence all exons (frozen tissue) |
Lack of mutation associated with chromosomal gain Her2 |
| Board [101] |
19/49 |
38.7 |
3 |
16 |
|
ARMS-Scorpion (3 codons) (Frozen tissue) |
|
| Kalinsky [71] |
192/590 |
32.5 |
69 |
101 |
21 |
PCR-mass-spec (17 codons) |
ER+ Her2- LN- good prognosis; ex20:LN-, ex9:older age at dx |
| Miron [80] |
35/120 |
29.2 |
4 |
31 |
|
Oncomap (12 codons) |
|
| Li [64] |
29/108 |
26.9 |
|
|
|
Sequence exon 9, 20 (frozen tissue) |
ER+ PR+ |
| Bozhanov [102] |
45/144^ |
31.3 |
18 |
28 |
|
Sequence exon 9, 20 (Frozen tissue) |
PR+, trend for better outcome |
| Michelucci [68] |
68/176^ |
35.4 |
25 |
43 |
|
Direct sequence exon 9, 20 (mostly frozen) |
ER+ in Her2-; lobular subtype. No survival association |
| Kadota [10] |
25/161 |
15.5 |
|
|
|
|
|
| Jaiswal [50] |
14/62 |
22.5 |
2 |
10 |
2 |
Sequence all coding exons |
|
| Vorkas [65] |
62/174^ |
35.6 |
18 |
45 |
|
High resolution melt analysis, exon 9, 20 |
|
| Dunlap [79] |
12/81 |
14.2 |
4 |
8 |
|
DHPLC exon 7, 9, 20 |
No association ER, Her2, LN |
| Lopez-Knowles [11] |
12/168 |
7.1% |
4 |
8 |
|
Sequence exon 9, 20 |
No association with intrinsic cancer subtype |
| Kan [50] |
29/183 |
15.8 |
|
27 |
2 |
Mismatch Repair Detection (frozen tissue) |
|
| Boyault [103] |
22/120 |
18.3 |
10 |
12 |
|
Sequence exon 9, 20 (frozen tissue) |
ER+ |
| Board [101] |
14/47 |
29.8 |
5 |
9 |
|
ARMS (3 codons) |
Control group for study of metastatic tumors |
| Total |
1309/4966 |
26.3 |
460 |
725 |
73 |
|
|
| B. Studies of selected tumor phenotypes |
| Author |
PIK3CA mutations |
Exon |
Methods |
Tumor phenotype; PIK3CA mutation positive &clinical variables |
# mutations/ positive &clinical variables
cases tested |
% |
9 |
20 |
Other |
|
|
| Berns [84] |
14/55 |
25 |
4 |
10 |
|
|
Study of trastuzumab treated patients |
| Lerma[105] |
7/56 |
12 |
1 |
6 |
|
Sequence exons 9, 20 |
Study of Her2+, Triple Negative
Associated with Her2+ and worse outcome |
| Hennessy [46] |
9/19 |
47 |
5 |
5 |
|
PCR-mass-spec (~21 codons) (frozen tissue) |
Study of metaplastic carcinoma |
DiNicolantonio
[106] |
1/15 |
6.7 |
|
1 |
|
Sequence exon 9, 20 |
Study of advanced stage everolimus treated
patients |
| Toi [27] |
5/29 |
17.2 |
|
3 |
2 |
Sequence exons 9, 14-20 |
Study of laptinib in Stage IIIb+ progressing on
anthracyclines or taxanes |
| Michelucci [68] |
2/22 |
|
1 |
1 |
|
Direct sequence exon 9, 20 (mostly frozen) |
Hereditary breast cancers (both mutations in
BRCA2, 0/10 BRCA1) |
| Ellis [73] |
127/398 |
32 |
46 |
85 |
1 |
Sequence exon 9, 20 |
Study of ER+ endocrine trial cases. Exon 20
improved DF survival |
| Loi [57] |
46/173^ |
26 |
14 |
32 |
|
SSCP exon 9, 20 |
Study of ER+/Her2- only. PIK3CA mutation
gene signature good prognosis. |
| Esteva [12] |
12/55 |
21.8 |
5 |
7 |
|
Sequencing exon 9, 20 |
Study of Her2+ trastuzumab treated breast
cancers |
| Da Silva [74] |
2/12 |
16.7 |
1 |
1 |
|
PCR-mass-spec (13 codons) |
Study of primary tumors with brain metastasis |
Dupont-Jensen
[75] |
45/101 |
45 |
15 |
36 |
|
SNaPshot PCR 3 codons |
Study of primary tumors with subsequent
metastasis |
| Cizkova^ [58] |
106/292 |
36.3 |
44 |
46 |
|
Sequence exon 9, 20 (frozen tissue)
Exons only provided for validation cohort (n-
249) |
Study of ER+ tumors. Characterizes PIK3CA
mutation gene signature. |
| Razis [86] |
38/175 |
21.7 |
|
|
|
Taqman SNP, 3 codons |
Study of trastuzumab treated metastatic
tumors. ER+, decreased time to progression |
| Wang [87] |
7/57 |
12.2 |
2 |
5 |
|
Sanger sequencing exon 9, 20 (2 non-hotspot
mutations identified) |
Study of Her2+ trastuzumab, taxane and
anthracycline treated. |
Gonzalez-Angulo
[76] |
19/47 |
40.4 |
1 |
18 |
|
PCR-mass-spec (~21 codons) |
Study of primary tumors with subsequent
metastasis |
| Duprez [66] |
22/49 |
44.8 |
12 |
10 |
|
PCR-mass-spec (13 codons) |
Study of papillary carcinomas |
| Duprez [66] |
14/49 |
28.5 |
1 |
13 |
|
PCR-mass-spec (13 codons) |
Study of low grade infiltrating ductal
carcinomas |
| Board [101] |
10/45 |
23 |
7 |
3 |
|
ARMS-Scorpion (3 codons) |
Study of metastatic carcinomas |
A. Unselected primary breast carcinomas