Table 2.

Summary of meta-analyses evaluating the relationship of HER2 alteration on outcome with anthracycline vs non-anthracycline.

Study (Year)	Ref	Studies Included	Dz Setting	N	Outcomes	Notes regarding testing
Gennari 2008 J Natl Cancer Inst	89	NSABP B11 NSABP B15 GUN3 (OS only) Belgian (DFS only) Milan DBCG 89D GOIRC (OS only-methodologic issues w/ DFS) MA-5	ADJ	4286 DFS 4321 OS	DFS anthracycline vs non-anthracycline HER2+ HR = 0.71 HER2− HR = 1.00; p int <0.001 OS anthracycline vs non-anthracycline HER2+ HR = 0.73 HER2− HR = 1.03; p int <0.001	Pooled analysis No centralized reassessment of HER2 IHC and/or FISH used
Dhesy-Thind 2008 Breast Cancer Res Treat	90	MA-5 (N = 628) Milan (N = 506) NSABP-B11 (N = 638) NSABP-B15 (N = 1355) Belgian (DFS only) (included only EC and CMF arms and only results as tested by FISH, N = 237) DBCG 89d (N = 805) GUN-3 (OS only)a (N = 123) GOIRC (OS only) (N = 266)	ADJ	4169 (DFS) 4321 (OS)	Significant benefit for anthracycline in HER2+: DFS HR = 0.71; (95% CI 0.60,0.83) OS HR = 0.73; (95% CI 0.62–0.86) No significant benefit of anthracyclines for HER2 negative
Di Leo 2011 Lancet Oncol	87	Belgian MA-5 DBCG 89d NEAT BR9601	ADJ	3452	EFS anthracycline vs CMF HER2+ HR = 0.71 HER2− HR = 0·89; p int = 0.0485 OS anthracycline vs CMF: HER2+ HR = 0·73 HER2- HR = 0·91; p int = 0.0718	Tested all samples centrally Better concordance between external lab and national laboratories when whole tumor sections used rather than TMAs. Concordance 94% in a subset (N = 137) sampled at external and national lab HER2 FISH >2 = positive

ADJ adjuvant, C cyclophosphamide, DFS disease-free survival, E epirubicin, F fluorouracil, FISH fluorescent in situ hybridization, HR hazard ratio, IHC immunohistochemistry, M methotrexate, MBC metastatic breast cancer, NR not reported, OS overall survival, pac paclitaxel, RFS relapse-free survival, TMA tissue microarray.