Table III

HER-2/neu status and prognosis in breast cancer

Study/yearFirst author/ref.No. of casesSpecimen typeMethod(s) of analysisUnivariate significanceMultivariate significanceComment
1 1987Slamon 60189FrozenSouthern blotYesYesHER-2 amplification predicted overall survival and time to relapse
2 1988Berger 6151Frozen paraffinSouthern blot IHCYesHER-2 protein by IHC correlated with node status and tumor grade
3 1988van de Vijver 62189ParaffinIHCNoNoCorrelated with size, comedocarcinoma
4 1989Wright 63185ParaffinIHCYesYesOverexpression correlated with high grade, negative ER, not size or node status
5 1990Heintz 6450FrozenSouthern analysisNoNoMitoses, ER/PR-negative
6 1990Tsuda 65176ParaffinSouthern analysisYesNoImpact on prognosis absorbed by grade
7 1990Borg 66300FreshWesternYesNoGene amplification predicted relapse and death in node-negative on univariate only
8 1990Paik 67292ParaffinIHCYesYesHER-2 protein overexpression second only to nodal status in predicting outcome
9 1991Battifora 68245ParaffinIHCYesYesSignificant only for low-grade, low-stage cases
10 1991Kallionemi 69319ParaffinIHCYesYesIndependent predictor in node-negative and -positive
11 1991Gullick 70483ParaffinIHCYesYesOverexpression correlated with grade, but not size, ER, or nodal status
12 1991Clark 71362FreshSlot blotNoNoAmplification marginally predictive in node-positive only
13 1991Lovekin 72782ParaffinIHCYesYesHER-2 overexpression predicted outcome in early and advanced cases; grade more significant predictor
14 1991McCann 73314ParaffinIHCYesYesPredicted outcome in node-negative and node-positive
15 1991Dykens 74178ParaffinIHCYesYesOverexpression predicted shortened survival in node-negative, but not in node-positive patients
16 1991Rilke 751,210ParaffinIHCYesNoProtein overexpression predicted outcome in node-positive only
17 1991Winstanley 76465ParaffinIHCYesYesHER-2 protein staining independently predicted survival
18 1991O’Reily 77172ParaffinIHCYesYesHER-2 protein overexpression predicted outcome in node-positive, but not in node-negative disease
19 1991Patterson 78115ParaffinSlot blotYesYesGene amplification predicted disease-free interval in node-negative patients
20 1992Toikkanen 79209ParaffinIHCYesYesProtein overexpression predicted shortened survival in node-positive patients
21 1992Molina 80301ParaffinIHCYesYesBoth methods of protein levels predicted worse overall survival
22 1992Noguchi 81234ParaffinIHCYesNoOnly nodal status correlated independently
23 1992Allred 82613ParaffinIHCYesSignificant for node-negative low-risk only
24 1992Babiak 8378ParaffinSlot blotYesOnly when combined with aneuploid status
25 1992Tiwari 8461FrozenSouthernYesHER-2 amplification associated with nodal metastasis
26 1992Gusterson 851,506ParaffinIHCYesYesPredicted outcome in node-positive only
27 1993Bianchi 86230ParaffinIHCYesNoOnly diffuse intense staining correlated
28 1993Press 87210ParaffinIHCYesYesPredicts relapse in node-negative
29 1993Seshadri 881,056FreshSlot blotYesYesIndependent for both node-negative and -positive
30 1993Descotes 89298FrozenSlot blotYesYesWith PR-negative, node status
31 1994Giai 90159ParaffinWestern blotYesYesIndependent predictor in node-negative
32 1994Muss 91442ParaffinIHCYesPredicts response to chemotherapy
33 1994Tetu 92888ParaffinIHCYesYesSurvival in node-positive, only membranous pattern correlates
34 1994Hartmann 93340ParaffinIHCYesNoPredicts lymph node status
35 1994Jaquemeier 9481ParaffinIHCNoNoNo correlation with therapy response
36 1994Marks 95230ParaffinIHCYesYesp53 and node status also independent
37 1994Rosen 96440ParaffinIHCNoNoMedullary carcinoma is negative
38 1995Quenel 97942ParaffinIHCYesYesHER-2 predicted relapse-free and metastasis-free survival
39 1996Sundblad 98271ParaffinIHCYesYesNode-positive, HER-2/neu-negative, CEA-positive and bcl-2-positive had the best prognosis
40 1996O’Malley 99107ParaffinIHCYesYesBoth p53 and HER-2/neu staining independently predicted outcome
41 1996Hieken 100100Paraffin; cytosolIHCNoNoHER-2 protein by ELISA, not IHC predictive
42 1996Xing 10137ParaffinFISHYesHER-2 amplification more predictive than nodal status in young patients
43 1997Dittadi 102115CytosolELISAYesYesHER-2 protein levels predicted disease-free survival
44 1997Fernandez-Acenero 103112ParaffinIHCYesNoOnly TNM stage independent predictor
45 1997Eissa 104100CytosolELISAYesYesHER-2 strongest predictor of recurrence in node-negative
46 1997Charpin 105148FrozenIHCYesYesOverall and disease-free survival independent of nodal status
47 1997Press 106324ParaffinFISHYesYesHER-2/neu gene amplification predicts recurrence and death
48 1998Ross 107224ParaffinFISHYesYesThree-tiered amplification system
49 1998Depowski 108145ParaffinFISHYesYesHER-2 amplification predicted death independent of nodal status
50 1998Querzoli 109164ParaffinIHCYesYesHER-2 overexpression independently predicted recurrence and survival
51 1998Andrulis 110580FreshSouthernYesYesHER-2 amplification independently predicted recurrence in node-negative; impact more in adjuvant treated cases
52 1998Sjogren 111315ParaffinIHCYesYesCB-11 antibody IHC predicted overall survival independent of age, node status, size, grade, hormone receptor status, S phase, p53 status, and adjuvant therapy
53 1999Harbeck 112112ParaffinFISHYesYesHER-2 amplification by FISH and [plasminogen protease (uPA, PAI-1) levels were both independent predictors in node-negative patients
54 1999Scorilas 113136FreshSouthernYesNoCathepsin D was an independent predictor, but HER-2 was not
55 1999Rudolph 114356ParaffinIHCYesNoHER-2 overexpression not an independent predictor of prognosis
56 2000Reed 115385ParaffinIHCNoNoThe HER-2-positive rate was only 10% in the non-correlating IHC study
57 2000Pauletti 116189ParaffinIHCYesYesAmplification detected by FISH was consistently predictive of outcome, but IHC testing was not
58 2000Kakar 117117ParaffinIHCYesIHC 3+-positive and FISH-positive cases correlated with outcome; IHC 2+-positive cases did not
59 2000Agrup 118110ParaffinIHCYesYesHER-2 overexpression predicted survival in node-positive disease in young women independent of adjuvant therapy
60 2000Umekita 119159ParaffinIHCYesNoCo-expression of TGF-α and EGFR had worst prognosis
61 2000Pawlowski 120365FreshRT-PCRNoNoHER-2 mRNA levels correlated with grade and ER/PR status but not survival; increased HER-4 levels were a favorable prognostic finding
62 2000Volpi 121286ParaffinIHCYesNoHER-2 status predictive of short-term prognosis only and not an independent predictor
63 2000Carr 122190ParaffinFISHYesYesHER-2 amplification predicted recurrence independent of ER and LN status
64 2000Ferrero-Pous 123488FreshELISAYesYesHER-2 overexpression also predicted reduced response to Tamoxifen
65 2000Platt-Higgins 124349ParaffinIHCYesNoS1004A protein marker was an independent predictor; HDER-2 expression was significant on univariate analysis only
66 2001Eppenberger- Castori 1251,123FreshELISAYesYesHER-2 levels predicted survival independent of hormonal or cytotoxic therapy
67 2001Jukkola 126650FreshSouthernYesYesHER-2-positive patients also had reduced responses to both hormonal and cytotoxic therapies
68 2001Gaci 127100FreshELISAYesYesHER-2 and cathepsin D expression were both independent predictors of OS
69 2001Rudolph 128261ParaffinIHCYesYesCell cycling ratio was most predictive factor in multivariate analysis
70 2001Beenken 12990ParaffinIHCYesYesHER-2 and p53 co-expression had the worst prognosis
71 2001Pinto 130306ParaffinIHCYesYesHER-2-positive ER-positive patients had reduced response rate to Tamoxifen
72 2001Riou 131172FreshSouthernYesYesHE-2 amplification independently predicted survival; no correlation with survival for IHC positive cases with no gene amplification
73 2001Horita 13276ParaffinIHCYesYesHER-2 expression correlated with PCNA expression
74 2002Suo 133100ParaffinIHCYesYesCo-expression of HER-2 with EGFR (HER-1) had worse DFS
75 2002Ristimaki 1341,576ParaffinFISHYesYesHER-2 amplification was an independent predictor of survival and correlated with Cox-2 expression
76 2002Rosenthal 3371ParaffinFISHYesNoInvasive lobular cancer had lower HER-2 amplification rate (<10%) than invasive ductal cancer and reached near significance as an independent predictor of OS
77 2002Tsutsui 135698ParaffinIHCYesYesCombined HER-2-positive and ER-negative had the worst outcome
78 2002Spizzo 136205ParaffinIHCYesYesBoth HER-2 and Ep-CAM expression were independent predictors of OS
79 2002Kato 137408ParaffinIHCYesNoHER-2 status was an independent predictor in some but not all patient cohorts
80 2002El-Amady 13894FreshELISAYesYesHER-2 protein level by ELISA most predictive factor for short-term prognosis