| Study | Type | Design | Country | Clinical Stage | Cases (n) | Neoadjuvant treatment | Age | Arm | HER2+ % | HR+ % | Limitations of the Study | Ref |
| MD Anderson, 2005 & 2007 | Peer reviewed | Open-label | United States | II-IIIA | 42 | CT C | 52 48 | 23 19 | 100 100 | 56 58 | Small sample size, unoptimal imaging modalities or cancer markers used, unclear description about building of outcome assessment, premature termination | [40, 41] |
| Pierga, 2010 | Peer reviewed | Multicentre, open-label, phase II | France | II-III | 120 | CT C | 47 47 | 62 58 | 100 100 | 55 63 | Absence of long-term outcome | [42] |
| NOAH, 2010 & 2014 | Peer reviewed | Multicentre, open-label, phase III | Europe and North America 6 counties | T3N1 or T4 or any T N2-3 | 235 | CT C | NR | 117 118 | 100 | 35 35 | Unclear description about building of outcome assessment. | [43, 44] |
| H2269s, 2010 | Peer reviewed | Open-label | United States | T2-4 | 29 | CT C | 50 | 15 14 | 100 | NR | Small sample size, absence of HR status data, unclear description about building of outcome assessment, different pCR definition used, absence of long-term outcome | [45, 46] |
| LPT 109096 2011 | Abstract | Multicentre, open-label, phase II | United States | T2-4, N0-2 | 100 | CTL CT CL | 49 51 51 | 33 33 34 | 100 | NR | Full-text unavailable, small sample size. | [47] |
| GeparQuinto–GBG44 2012 | Peer reviewed | Multicentre, open-label, phase III | Germany
| T1 pNSLN+, T2cN+, T3-4, | 615 | CT CL | 50 50 | 309 311 | 100 100 | 55 56 | Unmasked allocation concealment, absence of long-term outcome | [48] |
| NeoALTTO, 2012 & 2014 | Peer reviewed | Multicentre, open-label, phase III | International 25 countries | T2-4 | 455 | CTL CT CL | 50 49 50 | 152 149 154 | 100 100 100 | 51 50 52 | More patients had to stop treatment due to side-effects in the lapatinib-containing groups | [49, 50] |
| CHER-LOB, 2012 | Peer reviewed | Multicentre, open-label phase IIb | Italy
| II-IIIA | 121 | CTL CT CL | 49 50 49 | 46 36 39 | 100 100 100 | 61 58 62 | Small sample size, absence of HR status data, absence of long-term outcome | [51] |
| NeoSphere, 2012 & 2016 | Peer reviewed | Multicentre, open-label, phase II | International 19 countries | T2-4 | 417 | CTL TP CT CP | 50 49 50 49 | 107 107 107 96 | 100 100 100 100 | 47 47 47 48 | Not been identified | [52, 53] |
| NSABP B41, 2013 | Peer reviewed | Muticentre open-label, phase III | North America 3 countries | T2-T3, N0-N2a | 519 | CTP CT CL | NR | 174 181 174 | 100 100 100 | 62 67 58 | Unmasked allocation concealment, unclear description about building of outcome assessment, | [54] |
| TRIO-US B07, 2013 | Abstract | Multicentre, open-label, phase II | United States | I-III | 106 | CTL CT CL | NR | 58 34 36 | 100 100 100 | NR | Unbalanced baseline characteristic, small sample size, absence of HR status data, absence of long-term outcome | [55] |
| ABCSG-24, 2013 | Peer reviewed | Multicentre open-label, phase III | Austria
| T1-4 | 93 | CT C | 50 48 | 44 49 | 100 100 | 41 38 | Small sample size, key regimen is not used internationally, absence of long-term outcome | [56] |
| GEICAM, 2014 | Peer reviewed | Multicentre, open-label, phase II | Spain
| I-III or inflammatory | 99 | CT CL | 49 48 | 50 52 | 100 100 | 60 56 | Absence of long-term outcome, small sample size | [57] |
| EORTC 10054, 2014 | Peer reviewed | Multicentre, open-label, phase IIb | Europe 5 countries | IIA-IIC | 122 | CTL CT CL | 49 47 50 | 52 53 23 | 100 100 100 | 52 52 68 | Unbalanced baseline characteristic, small sample size, premature termination, absence of long-term outcome | [58] |
| KRISTINE, 2016 | Abstract | Multicentre, open-label, phase III | International, 11 countries | II-IIIC | 444 | MP CTP | NR | 223 221 | 100 100 | 51 49 | Full-text unavailable | [59, 60] |
| CALGB 40601, 2016 | Peer reviewed | Multicentre, open-label, phase III | United States | II-III | 295 | CTL CT CL | 48 50 50 | 118 120 67 | 100 100 100 | 59 59 58 | Premature termination, absence of long-term outcome | [61] |
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Note. C indicates chemotherapy alone; CL, chemotherapy plus lapatinib; CP, chemotherapy plus pertuzumab; CT, chemotherapy plus trastuzumab; CTL, chemotherapy plus trastuzumab plus lapatinib; CTP, chemotherapy plus trastuzumab plus pertuzumab; HER2, human epidermal growth factor receptor-2; HR, hormone receptor; MP, trastuzumab emtansine plus pertuzumab; NR, not reported; TP, trastuzumab plus pertuzumab.
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