Table 2.
Series | Description | Covariate | DMFS P value⁎ | DMFS HR (95% CI) | OS P value† | OS HR (95% CI) |
---|---|---|---|---|---|---|
Training: GSE4922, Ivshina et al,12; GSE6532, Loi et al11 (N = 477) | ER+/ER-, N0/N1, systemic therapy, tamoxifen only, or no adjuvant therapy | Age | 0.42 | 1.01 (0.99–1.02) | ||
ER+ | 0.58 | 1.18 (0.65–2.16) | ||||
Grade | 0.059 | 1.40 (0.99–1.97) | ||||
Size | 0.10 | 1.01 (1.00–1.02) | ||||
Node+ | 0.0001‡ | 2.79 (1.67–4.66)‡ | ||||
Endocrine therapy | 0.28 | 0.73 (0.42–1.28) | ||||
Chemotherapy | 0.0032‡ | 0.35 (0.18–0.70)‡ | ||||
200-Gene signature | 0.0001‡ | 3.14 (1.80–5.49)‡ | ||||
Validation 1: GSE7390, Desmedt et al13 (N = 198) | ER+/–, N0, <61 years, untreated, ≤5 cm | Age | 0.35 | 1.022 (0.98–1.07) | 0.46 | 1.02 (0.97–1.06) |
ER+ | 0.54 | 0.81 (0.40–1.62) | 0.033‡ | 0.48 (0.25–0.94)‡ | ||
Grade | 0.73 | 1.11 (0.63–1.95) | 0.23 | 0.74 (0.45–1.21) | ||
Size | 0.092 | 1.35 (0.95–1.92) | 0.074 | 1.35 (0.97–1.87) | ||
200-Gene signature | 0.0046‡ | 4.37 (1.58–12.08)‡ | 0.0053‡ | 3.31 (1.43–7.64)‡ | ||
Validation 2: GSE11121, Schmidt et al14 (N = 200) | ER+/–, untreated, population based, N0 | Grade | 0.033‡ | 1.93 (1.057–3.51)‡ | ||
Size | 0.79 | 1.044 (0.75–1.45) | ||||
200-Gene signature | 0.056 | 2.63 (0.98–7.055) | ||||
Validation 3: GSE1456, Pawitan et al15 (N = 159) | ER+/–, population based, 126 received adjuvant therapy | Grade | 0.19 | 1.47 (0.83–2.64) | 0.34 | 1.40 (0.70–2.80) |
200-Gene signature | 0.055 | 2.58 (0.98–6.67) | 0.025‡ | 4.67 (1.23–17.81)‡ | ||
Validation 4: GSE9195 and GSE6532, Loi et al11 (N = 128) | ER+, adjuvant tamoxifen treated, N0/N1, ≤5 cm | Age | 0.22 | 0.97 (0.93–1.019) | ||
Grade | 0.74 | 0.89 (0.46–1.72) | ||||
Nodes | 0.94 | 0.96 (0.38–2.38) | ||||
Size | 0.0075‡ | 1.49 (1.11–1.98)‡ | ||||
200-Gene signature | 0.019‡ | 6.51 (1.37–30.86)‡ | ||||
Validation 5: NKI 295, Van De Vijver et al16 (N = 295)§ | ER+/–, untreated, stage I/ II, <53 years; N0/N1 | ER+ | 0.18 | 0.74 (0.47–1.16) | 0.057 | 0.51 (0.32–0.82) |
Node+ | 0.39 | 0.84 (0.56–1.25) | 0.63 | 0.90 (0.57–1.40) | ||
99-Gene signature | <0.0001‡ | 2.92 (1.77–4.80)‡ | <0.0001‡ | 3.91 (2.06–7.42)‡ |
GSE numbers are the National Center for Biotechnology Information Gene Expression Omnibus entry for each series.
GSE, GEO Series; N0, lymph node negative; N1, lymph node positive; NKI, Nederlands Kanker Instituut (Netherlands Cancer Institute).
Value for RFS in the training series and for DMFS in the validation 1, 3, 4, and 5 series.
Value for OS in the validation 1 and 5 series and DSS in the validation 3 series. OS details for other series not available.
Statistically significant variables within each CPH model.
Validation series 5 was generated using a custom oligonucleotide microarray containing 99 of the 200 genes used by the classifier.
Data were obtained from Rosetta Inpharmatics, Seattle, WA (http://www.rii.com/publications/2002/nejm.html, last accessed March 3, 2011).