Table 1 Characteristics of the eligible studies

Rouzier R [8]

2005

I, II, III

12 weeks of P followed by FAC 4 courses (weekly P (80 mg/m²) × 12 + FAC × 4 or 3 weekly P (225 mg/m²) × 4 + FAC × 4)

10

12

45.50%

11

49

18.30%

3.71 (1.28, 10.76)

Carey LA [1]

2007

II, III

A 60 mg/m² + C 600 mg/m² every 2 weeks or 3 weeks for 4 cycles, either alone or as the first component of a sequential AC-taxane neoadjuvant regimen

9

25

26.50%

8

69

10.40%

3.10 (1.08, 8.93)

Goldstein NS [12]

2007

IIA to IIIC

FAC every 3 weeks × 6 FEC every 3 weeks × 6 AC every 2 weeks (dose dense) × 4 then paclitaxel every 2 weeks (dose dense) × 4 AC every 3 weeks × 4 then P every 1 week × 4

12

9

57.10%

16

31

34.00%

2.58 (0.90, 7.41)

Keam B [13]

2007

II, III

D (75 mg/m² or 60 mg/m²) and A (60 mg/m² or 50 mg/m²) by intravenous infusion every 3 weeks for 3 cycles

8

39

17.00%

3

95

3.10%

6.50 (1.64, 25.78)

Liedtke C [9]

2008

I, II, III

FAC; FEC; weekly or once every 3 weeks P/D followed by FAC; weekly or once every 3 weeks P/D followed by FEC

57

198

22.40%

98

765

11.40%

2.25 (1.56, 3.23)

Bidard FC [14]

2008

I, II, III

FEC (F 500 mg/m², E 100 mg/m², C 500 mg/m²) or FAC (F 500 mg/m², A 60 mg/m², C 500 mg/m²), every 3 weeks for 4 to 6 cycles

21

99

17.50%

7

166

4.00%

5.03 (2.06, 12.26)

Julka PK [15]

2008

IIA to IIIB

4 cycles (21 days) of Gem 1,200 mg/m² + A 60 mg/m², 4 cycles of Gem 1,000 mg/m² plus Cis 70 mg/m²

7

7

50.00%

6

16

27.30%

2.67 (0.65, 10.88)

Sánchez-Muñoz A [16]

2008

II, III

Schedule A: E 90 mg/m² + C 600 mg/m² d1 for 3 cycles followed by a second sequence with P 150 mg/m² + Gem 2,500 mg/m² d1 ± trastuzumab 2 mg/kg/week according to HER2 status Schedule B: A 40 mg/m² d1 + P 150 mg/m² + Gem (2,000 mg/m²) d2, 2 weekly for 6 cycles

14

10

58.30%

17

58

22.70%

4.78 (1.80, 12.66)

Sirohi B [17]

2008

M0

F 200 mg/m² daily with E 60 mg/m² and Cis 60 mg/m² both repeating 3 weekly for 6 courses

1

5

16.70%

5

49

9.30%

1.96 (0.19, 20.26)

Darb-Esfahani S [18]

2009

T2 to 3, N0 to 2, M0

A 50 mg/m² + D 75 mg/m² every 14 days for 4 cycles or 4 cycles A 60 mg/m² plus C 600 mg/m² every 21 days followed by D 100 mg/m² every 21 days for 4 cycles

8

25

24.20%

5

78

6.00%

4.99 (1.50, 16.65)

Sikov WM [19]

2009

IIA to IIIB

Cb (AUG = 6) every 4 weeks and P 80 mg/m² weekly for 16 weeks, and weekly trastuzumab was added for HER2(+) status

8

4

66.70%

16

25

39.00%

3.13 (0.81, 12.11)

Bhargava R [20]

2010

I, II, III

Anthracycline-based therapy: AC, FEC; taxane-based therapy: T/P + Cb. In many cases a sequential combination of anthracycline and taxane was given: AC-T. The total number of cycles ranged from 4 to 10 with an average of 6

24

55

30.40%

24

256

8.60%

4.65 (2.46, 8.80)

Chang HR [21]

2010

II, III

D (75 mg/m²) and Cb (AUC = 6) were administered every 3 weeks for 4 cycles. Patients with HER2(+) tumors were randomized to receive either additional weekly trastuzumab preoperatively or TC alone

6

5

54.50%

13

47

21.70%

4.34 (1.14, 16.51)

Chavez-Macgregor M [22]

2010

M0

Taxane administered: P 175 to 250 mg/m² on d1, 3 weekly for 4 cycles; P 80 mg/m² weekly for 12 doses; or D 100 mg/m² on d1, 3 weekly for 4 cycles Anthracycline regimens (3 to 6 cycles): F 500 mg/m², E 100 mg/m² and C 500 mg/m² on d1, d3 weekly; F 500 mg/m² on d1, d4, E 75 mg/m² and C 500 mg/m² on d1, 3 weekly

95

395

19.40%

165

1419

10.40%

2.07 (1.57, 2.73)

Chen XS [23]

2010

T3 to 4, any N, M0;

any T, N2 to 3, M0

VE: V 25 mg/m² d1, d8 + E 60 mg/m² d1, d3 weekly; PCb: P 80 mg/m² + Cb AUC = 2 d1, d8, d15, 4 weekly; CEF: C 500 mg/m², E 75 mg/m² and F 500 mg/m² d1, 3 weekly; CTF: C 500 mg/m², THP 50 mg/m², and F 500 mg/m² d1, 3 weekly; CEF➝T: D 75 mg/m² d1, 3 weekly; ED: E 60 mg/m² + D 75 mg/m², 3 weekly

9

44

17.00%

19

153

11.00%

2.07 (0.86, 4.96)

Huober J [24]

2010

I, II, III

6 to 8 cycles of TAC (D 75 mg/m², A 50 mg/m², C 500 mg/m² on d1, every 3 weeks) or 2 cycles of TAC followed by four cycles of V 25 mg/m2 on d1, d8 + capecitabine 1,000 mg/m² orally twice a day on d1 to d14 every 3 weeks

198

311

38.90%

147

820

15.20%

3.55 (2.77, 4.56)

Kim SI [25]

2010

M0

A (50 mg/m², d1) + D (75 mg/m², d1) chemotherapy (AT) every 3 weeks for 3 cycles

16

60

21.10%

10

181

5.20%

4.83 (2.08, 11.21)

Pierga JY [26]

2010

II, III

E (75 mg/m²) + C (750 mg/m²) intravenously every 3 weeks for 4 cycles followed by D (100 mg/m²) every 3 weeks for 4 cycles with or without trastuzumab (8 mg/kg at first infusion then 6 mg/kg) every 3 weeks

23

55

29.50%

14

57

19.70%

1.70 (0.80, 3.64)

Straver ME [27]

2011

T1 to 3, N0 to 2, M0

AC (6 cycles of A 60 mg/m² and C 600 mg/m² every 3 weeks) or AD (6 cycles of A 50 mg/m² and D 75 mg/m², every 3 weeks)

16

41

28.10%

13

181

6.70%

5.43 (2.43, 12.17)

Bernsdorf M [28]

2011

T2 to 3, N0 to 3b, M0

4 cycles of EC (E 90 mg/m² and C 600 mg/m²) plus 12 weeks of daily treatment with gefitinib 250 mg or EC plus 12 weeks’ treatment with placebo. Chemotherapy was administered every 3 weeks

12

70

14.60%

1

47

2.10%

8.06 (1.01, 64.06)

Iwata H [29]

2011

T1c to 3, N0, M0; T1 to 3, N1, M0

4 cycles of D (75 mg/m²) administered intravenously every 21 days followed by 4 cycles of FEC (F 500 mg/m², E 100 mg/m² and C 500 mg/m²) administered intravenously on d1 every 21 days before surgery

14

15

48.30%

16

84

16.00%

4.90 (1.99, 12.09)

Loo CE [30]

2011

T2 to 4, N1 to 3, M0

Either ER(+) or (–), received 6 courses of AC, administered in a dose-dense schedule (every 2 weeks). A minority received 6 courses of capecitabine + D or doxorubicin + D

16

41

28.10%

22

119

15.60%

2.11 (1.01, 4.40)

Medioni J [31]

2011

II, III

Six 2-weekly courses of Gem 1,000 mg/m² + D 75 mg/m² on d1, d15 and V 25 mg/m² + E 100 mg/m² on d29, d43. Patients with an objective response on d56 then received another cycle of Gem + D on d57 and V + E on d71

9

13

40.90%

7

43

14.00%

4.25 (1.32, 13.65)

Nakahara H [32]

2011

T1 to 4

HER2(–) tumors started with CE (E 75 mg/m2 × d1 + C 100 mg × daily for 14 days with 7 days’ rest) for 4 or 6 cycles. HER2(+) tumors initiated with CE (E 90 mg/m² × d1 or E 50 mg/m² × d1, d8 and C 100 mg × daily for 14 days with 7 days’ rest)

5

13

27.80%

3

65

4.40%

8.33 (1.77, 39.27)

Wu J [33]

2011

II, III

P (175 mg/m²) or D (75 mg/m²) + doxorubicin (60 mg/m²) or E (90 mg/m²) every 21 days for a total of 4 cycles

14

40

25.90%

24

171

12.30%

2.49 (1.19, 5.25)

Le Tourneau C [34]

2012

II, III

4 cycles of intensified FAC (A 70 mg/m² d1, C 700 mg/m² d1 + d8, and F 700 mg/m² d1 to d5) every 3 weeks

9

10

47.40%

3

30

9.10%

9.00 (2.03, 39.93)

Ono M [35]

2012

II, III

Anthracycline-based regimen (AC: A 60 mg/m² + C 600 mg/m² or CEF: C 600 mg/m² + E 100 mg/m² + F 600 mg/m²) Taxane-based regimen (weekly P 80 mg/m² or triweekly D 75 mg/m²) Anthracycline and taxane sequentially or concurrently (A 50 mg/m² + D 60 mg/m², AC or CEF followed by weekly P or triweekly D)

26

66

28.30%

9

70

11.40%

3.06 (1.34, 7.02)