Study (primary publication) | Treatments | Node name in network | Median follow-up (months) | N total | Median age (years) | Tumor Size > 2 cm (%) | Node + (%) | HR+ (%) | HER2+ (%) |
---|---|---|---|---|---|---|---|---|---|
RCTs with 100% HER2+ early breast cancer patients | |||||||||
ALTTO (Piccart-Gebhart 2016) [66] | Anthracycline and/or taxane → trastuzumab IV (52 weeks) | AC-TH52 weeks | 54 | 2097 | 51 | 49 | 51 | 57 | 100 |
Anthracycline and/or taxane → lapatinib (52 weeks) | AC-TL52 weeks | 54 | 2100 | 51 | 51 | 52 | 57 | 100 | |
Anthracycline and/or taxane → trastuzumab IV (12 weeks) → lapatinib (34 weeks) | AC-TL34 weeks-H12 weeks | 54 | 2091 | 51 | 50 | 52 | 58 | 100 | |
Anthracycline and/or taxane → trastuzumab IV (52 weeks) + lapatinib (52 weeks) | AC-TL52 weeks-H52 weeks | 54 | 2093 | 51 | 50 | 51 | 57 | 100 | |
BCIRG 006 (Slamon 2011) [44] | Doxorubicin + cyclophosphamide → docetaxel | AC-T | 65 | 1073 | NR | 59 | 71 | 54 | 100 |
Doxorubicin + cyclophosphamide → docetaxel + trastuzumab IV (52 weeks) | AC-TH52 weeks | 65 | 1074 | NR | 62 | 71 | 54 | 100 | |
Docetaxel + carboplatin + trastuzumab IV (52 weeks) | TCH52 weeks | 65 | 1075 | NR | 59 | 72 | 54 | 100 | |
FNCLCC-PACS 04 (Spielmann 2009) [67] | FEC or ED (epirubicin + docetaxel) → trastuzumab IV (52 weeks) | AC-TH52 weeks | 47 | 260 | 48 | 59·1 | 100 | 58 | 100 |
FEC or ED (epirubicin + docetaxel) | AC-T | 47 | 268 | 49 | 50·6 | 100 | 61 | 100 | |
HannaH (Jackisch 2016) [68] | Docetaxel → FEC + trastuzumab IV → trastuzumab IV (52 weeks) | AC-TH52 weeks | 40·6 | 297 | 50 | NR | 79·1 | 49·8 | 100 |
Docetaxel → FEC + trastuzumab SC → trastuzumab SC (52 weeks) | AC-THSC,52 weeks | 40·3 | 294 | 50 | NR | 75·8 | 52·4 | 100 | |
HERA (Goldhirsch 2013) [64] | Anthracycline or taxane → trastuzumab IV (104 weeks) | AC-TH104 weeks | 96 | 1700 | NR | 49·5 | 56·5 | 51·4 | 100 |
Anthracycline or taxane → trastuzumab IV (52 weeks) | AC-TH52 weeks | 96 | 1702 | 49 | 48·4 | 56·4 | 50·9 | 100 | |
Anthracycline or taxane | AC-T | 96 | 1697 | 49 | NR | NR | NR | 100 | |
HORG (Mavroudis 2015) [70] | FEC → docetaxel + trastuzumab IV (52 weeks) | AC-TH52 weeks | 47 | 241 | 54 | NR | 74·7 | 64·7 | 100 |
FEC → docetaxel + trastuzumab IV (26 weeks) | AC-TH26 weeks | 51 | 240 | 56 | NR | 83·3 | 68·8 | 100 | |
NCCTG N9831 and NSABP B-31 (Perez 2014) [51] | Doxorubicin + cyclophosphamide → paclitaxel | AC-T | 99·6 | 2018 | ~ 50 | 59·2 | 92·6 | 54·8 | 100 |
Doxorubicin + cyclophosphamide → paclitaxel + trastuzumab IV (52 weeks) | AC-TH52 weeks | 100·8 | 2028 | ~ 50 | 61.8 | 93·4 | 54·7 | 100 | |
NeoALTTO (de Azambuja 2014) [72] | Paclitaxel → FEC → lapatinib (52 weeks) | AC-TL52 weeks | 45 | 154 | 50 | 100 | > 16·2 | 51·9 | 100 |
Paclitaxel → FEC → trastuzumab IV (52 weeks) | AC-TH52 weeks | 45 | 149 | 49 | 100 | > 15·4 | 50·3 | 100 | |
Paclitaxel + → FEC → lapatinib (52 weeks) + trastuzumab IV (52 weeks) | AC-TL52 weeks-H52 weeks | 45 | 152 | 50 | 100 | > 15·8 | 50·7 | 100 | |
NOAH (Gianni 2014) [20] | Paclitaxel + doxorubicin → paclitaxel → CMF | AC-T | 64·8 | 118 | NR | NR | 84 | 36 | 100 |
[Paclitaxel + doxorubicin → paclitaxel → CMF → trastuzumab IV (52 weeks) | AC-TH52 weeks | 64·8 | 117 | NR | NR | 86 | 36 | 100 | |
NSABP B-41 (Robidoux 2013b) [94] | Doxorubicin + cyclophosphamide → paclitaxel → trastuzumab IV (52 weeks) | AC-TH52 weeks | 22·8 | 181 | NR | 100 | 51 | 67 | 100 |
Doxorubicin + cyclophosphamide → paclitaxel + lapatinib (12 weeks) → trastuzumab IV (34 weeks) | AC → T-L12 weeks-H34 weeks | 22·8 | 174 | NR | 100 | 52 | 58 | 100 | |
Doxorubicin + cyclophosphamide → paclitaxel + lapatinib (12 weeks) + trastuzumab IV → trastuzumab IV (52 weeks) | AC → T-L12 weeks-H52 weeks | 22·8 | 174 | NR | 100 | 49 | 62 | 100 | |
PHARE (Pivot 2013) [75] | Anthracycline + taxane + trastuzumab IV → trastuzumab IV (52 weeks) | AC-TH52 weeks | 42·5 | 1690 | 54 | 45.3 | 44·6 | 60·4 | 100 |
Anthracycline + taxane + trastuzumab IV → trastuzumab IV (26 weeks) | AC-TH26 weeks | 42·5 | 1690 | 55 | 47·6 | 45.3 | 61·5 | 100 | |
RCTs with subgroup data of HER2+ early breast cancer patients | |||||||||
BCIRG 001 (Mackey 2013) [76] | Docetaxel + doxorubicin + cyclophosphamide | AC-T | 124 | 745 | 49 | 61 | 100 | 76·1 | 21 |
Fluorouracil + doxorubicin + cyclophosphamide | AC | 123 | 746 | 49 | 57 | 100 | 75·7 | 22 | |
Boccardo 2010 [77] | Epirubicin → cyclophosphamide + methotrexate + fluorouracil | AC | 102 | 122 | 53·0 | 47·5 | 100 | 79·5 | 31·1 |
Paclitaxel → epirubicin + vinorelbine | T → AV | 102 | 122 | 54·5 | 64.8 | 100 | 79·5 | 28·7 | |
BR9601 and NEAT (Earl 2012) [78] | Epirubicin → CMF | AC | 88·8 | 1189 | NR | 56 | 72 | ≥59 | 21 |
Cyclophosphamide + methotrexate + fluorouracil | CMF | 88·8 | 1202 | NR | 56 | 72 | ≥59 | 20 | |
Colozza 2005 [79] | Cyclophosphamide + methotrexate + fluorouracil | CMF | 96 | 133 | NR | 51 | 80 | ≥63 | 69 |
Epirubicin | E | 96 | 133 | NR | 48 | 78 | ≥63 | 77 | |
Del Mastro 2015 [80] | Epirubicin + cyclophosphamide → paclitaxel (q3w) | AC-T | 84 | 545 | 51 | 48 | 100 | 77 | 23 |
FEC → paclitaxel (q3w) | AC-T | 84 | 544 | 53 | 52 | 100 | 81 | 24 | |
Epirubicin + cyclophosphamide → paclitaxel (q2w) | Dose dense | 84 | 502 | 53 | 48 | 100 | 81 | 21 | |
FEC → paclitaxel (q2w) | Dose dense | 84 | 500 | 51 | 49 | 100 | 80 | 24 | |
E1199 (Sparano 2015c) [95] | Doxorubicin + cyclophosphamide → paclitaxel (weekly) | Dose dense | 145·2 | 1232 | 51 | 63.8 | 87.8 | 70·2 | 19·2 |
Doxorubicin + cyclophosphamide → paclitaxel (q3w) | AC-T | 145·2 | 1253 | 51 | 60.7 | 87.8 | 71·0 | 20·6 | |
E2198 (Schneider 2015) [82] | Paclitaxel + trastuzumab IV (10 weeks) → doxorubicin + cyclophosphamide | AC-TH9–10 weeks | 77 | 115 | 49 | NR | 100 | 60 | 53 |
Paclitaxel + trastuzumab IV (10 weeks) → doxorubicin + cyclophosphamide + trastuzumab IV (52 weeks total) | AC-TH52 weeks | 77 | 112 | 48 | NR | 100 | 63 | ||
FinHer (Joensuu 2009) [83] | Docetaxel → FEC | AC-T | 62 | 58 | 49·9 | 70 | 78 | ≥44 | 100a |
Docetaxel + trastuzumab IV (9 weeks) → FEC | AC-TH9–10 weeks | 62 | 54 | 51·4 | 59 | 90 | ≥50 | 100a | |
Vinorelbine → FEC | AC-V | 62 | 58 | 49·9 | 70 | 78 | ≥44 | 100a | |
Vinorelbine + trastuzumab IV (9 weeks) → FEC | AC-VH9 weeks | 62 | 62 | 51·4 | 59 | 90 | ≥50 | 100a | |
FinXX (Joensuu 2014) [84] | Capecitabine + docetaxel → cyclophosphamide + epirubicin + capecitabine → trastuzumab IV (52 weeks); or docetaxel → FEC → trastuzumab IV (52 weeks) | AC-TH52 weeks | 80·4 | 176 | 52·2 | NR | 84·6 | 60·2 | 100a |
Capecitabine + docetaxel → cyclophosphamide + epirubicin + capecitabine; or docetaxel → FEC | AC-T | 80·4 | 108 | 50·5 | NR | 81·4 | 51·9 | 100a | |
GeparTrio (von Minckwitz 2013) [85] | Docetaxel + doxorubicin + cyclophosphamide → vinorelbine + capecitabine (in non-responders) | AC-T → VX | 62 | 987 | NR | NR | 54·7 | 65·6 | 29·1 |
Docetaxel + doxorubicin + cyclophosphamide | AC-T | 62 | 1025 | NR | NR | 55·3 | 63·2 | 30·5 | |
GONO-MIG-1 (Del Mastro 2005) [86] | FEC (q3w) | AC | 80·4 | 53 | 54 | NR | 61·2 | ≥27·2 | 100a |
FEC (q2w) | Dose dense | 80·4 | 50 | 54 | NR | 61·2 | ≥27·2 | 100a | |
Miles 1999 [87] | Cyclophosphamide + methotrexate + fluorouracil | CMF | 159·6 | 129 | NR | 78 | 100 | ≥77·5 | 30 |
No treatment | No Tx | 159.6 | 145 | NR | 78 | 100 | ≥77·5 | 30 | |
Rocca 2014 [88] | Epirubicin → CMF, or CMF → epirubicin | AC | 69 | 545 | 53 | NR | 48·3 | ≥64·0 | 34·1 |
Cyclophosphamide + methotrexate + fluorouracil | CMF | 69 | 160 | 51 | NR | 47·5 | ≥56·9 | 30·0 | |
TEACH (Goss 2013) [89] | Lapatinib (52 weeks) + anthracycline/taxane | AC-TL52 weeks | 47.4 | 1571 | 51 | NR | 54 | 59 | 78 |
Placebo (52 weeks) + anthracycline/taxane | AC-T | 48·3 | 1576 | 52 | NR | 54 | 59 | 80 | |
UNICANCER-PACS01 (Coudert 2012) [90] | FEC | AC | 92·8 | 996 | NR | 57·8 | 100 | 78 | 9·4 |
FEC → docetaxel | AC-T | 92·8 | 1003 | NR | |||||
Non-randomized studies with 100% HER2+ early breast cancer patients | |||||||||
Bayraktar 2012 [91] | Paclitaxel + trastuzumab → FEC + trastuzumab (52 weeks) | AC-TH52 weeks | 29 | 235 | 49 | NR | 81·5 | ≥53·8 | 100 |
Docetaxel + carboplatin + trastuzumab (52 weeks) | TCH52 weeks | 18 | 65 | 53 | NR | 80.0 | ≥55·6 | 100 | |
Gonzalez-Angulo 2015 [92] | Adjuvant trastuzumab: paclitaxel + trastuzumab → FEC + trastuzumab (52 weeks) | AC-TH52 weeks | 45 | 480 | ~ 50 | NR | 19·4 | 61·1 | 100 |
No adjuvant trastuzumab: paclitaxel + trastuzumab (26 weeks) → FEC | AC-TH26 weeks | 45 | 109 | ~ 50 | NR | 15·6 | 53·2 | 100 | |
Seferina 2015 [93] | Anthracycline/taxane-containing chemotherapy + trastuzumab (52 weeks) | AC-TH52 weeks | 60 | 230 | 51 | > 56 | 56·0 | 62 | 100 |
Endocrine therapy and radiotherapy, no chemotherapy | No chemo | 60 | 246 | 65 | NR | NR | NR | 100 |