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Table 2 Cox regression analyses of BCFi and OS in patients randomised to no adjuvant medical treatment

From: Tumour-infiltrating lymphocytes as a prognostic and tamoxifen predictive marker in premenopausal breast cancer: data from a randomised trial with long-term follow-up

 

Univariable

Multivariablea

Variable

BCFi

OS

BCFi

OS

HR (95% CI); P value

TILs, categoryb

All subtypes

(n = 221)

(n = 213)

  Low (Ref.)

1.00

1.00

1.00

1.00

  Intermediate

1.10 (0.78–1.54); 0.61

1.26 (0.88–1.80); 0.21

0.61 (0.40–0.93); 0.02c

0.65 (0.41–1.02); 0.06

  High

0.40 (0.22–0.71); 0.002

0.52 (0.29–0.95); 0.03

0.22 (0.11–0.43); < 0.001

0.23 (0.11–0.48); < 0.001

ER+/HER2−

(n = 136)

(n = 135)

  Low (Ref.)

1.00

1.00

1.00

1.00

  Intermediate

1.02 (0.63–1.64); 0.94

1.02 (0.61–1.71); 0.95

0.69 (0.42–1.15); 0.16

0.65 (0.37–1.15); 0.14

  High

0.40 (0.14–1.09); 0.07

0.55 (0.20–1.52); 0.25

0.20 (0.06–0.60); 0.004

0.30 (0.10–0.96); 0.04

HER2+

(n = 38)

(n = 35)

  Low (Ref.)

1.00

1.00

1.00

1.00

  Intermediate

1.47 (0.62–3.49); 0.39

1.07 (0.45–2.56); 0.88

0.47 (0.14–1.60); 0.23

0.38 (0.11–1.31); 0.13

  High

0.28 (0.08–0.97); 0.05

0.27 (0.08–0.96); 0.04

0.06 (0.01–0.56); 0.01

0.05 (0.01–0.39); 0.005

TNBC

(n = 47)

(n = 43)

  Low (Ref.)

1.00

1.00

1.00

1.00

  Intermediate

0.76 (0.31–1.87); 0.55

1.24 (0.49–3.14); 0.65

0.59 (0.21–1.67); 0.32

1.02 (0.34–3.11); 0.97

  High

0.27 (0.08–0.88); 0.03

0.44 (0.14–1.36); 0.16

0.38 (0.11–1.39); 0.15

0.59 (0.16–2.26); 0.44

Covariables

(n = 216–221)

(n = 213)

  Age (years)

   < 40 (Ref.)

1.00

1.00

1.00

1.00

   ≥ 40

0.72 (0.49–1.04); 0.08

0.65 (0.44–0.96); 0.03

0.60 (0.40–0.89); 0.01

0.56 (0.37–0.85); 0.006

  Nodal status

   0 (Ref.)

1.00

1.00

1.00

1.00

   1–3

1.31 (0.87–1.96); 0.19

1.59 (1.03–2.47); 0.04

1.21 (0.77–1.91); 0.40

1.69 (1.03–2.77); 0.04

   ≥ 4

2.33 (1.49–3.64); < 0.001

2.81 (1.75–4.52); < 0.001

2.03 (1.25–3.29); 0.004

2.70 (1.58–4.52); < 0.001

  Tumour size (mm)

   ≤ 20 (Ref.)

1.00

1.00

1.00

1.00

   > 20

1.04 (0.75–1.45); 0.80

0.92 (0.66–1.29); 0.63

1.23 (0.86–1.76); 0.25

1.04 (0.72–1.51); 0.84

  Histological grade (NHG)

   1 (Ref.)

1.00

1.00

1.00

1.00

   2

1.51 (0.84–2.72); 0.17

1.34 (0.73–2.45); 0.35

1.36 (0.74–2.48); 0.32

1.13 (0.60–2.11); 0.71

   3

1.82 (1.03–3.23); 0.04

1.96 (1.09–3.54); 0.03

2.70 (1.36–5.33); 0.004

2.25 (1.08–4.66); 0.03

  ER

   Negative (Ref.)

1.00

1.00

1.00

1.00

   Positive

0.94 (0.66–1.34); 0.74

0.69 (0.49–0.99); 0.04

0.41 (0.12–1.36); 0.15

0.37 (0.11–1.27); 0.11

  PR

   Negative (Ref.)

1.00

1.00

1.00

1.00

   Positive

1.06 (0.75–1.49); 0.75

0.80 (0.57–1.14); 0.21

2.38 (0.77–7.30); 0.13

1.76 (0.57–5.48); 0.33

  HER2

   Negative (Ref.)

1.00

1.00

1.00

1.00

   Positive

1.10 (0.72–1.69); 0.65

1.26 (0.81–1.94); 0.30

1.05 (0.66–1.67); 0.85

1.11 (0.68–1.82); 0.67

  LVI

   Absent (Ref.)

1.00

1.00

1.00

1.00

   Present

1.49 (1.08–2.05); 0.02

1.26 (0.90–1.76); 0.18

1.39 (0.99–1.95); 0.06

1.05 (0.73–1.51); 0.78

  1. All analyses were stratified by study region
  2. Abbreviations: BCFi breast cancer free-interval, CI confidence interval, ER oestrogen receptor, HER2 human epidermal growth factor receptor 2, HR hazard ratio, LVI lymphovascular invasion, NHG Nottingham histological grade, OS overall survival, PR progesterone receptor, TILs tumour-infiltrating lymphocytes, TNBC triple-negative breast cancer
  3. aThe following variables were included in multivariable analysis: age (≥ 40 vs. < 40 years), nodal status (0 vs.1–3 vs. ≥ 4), tumour size (> 20 mm vs. ≤ 20 mm), histological grade (1 vs. 2 vs. 3), ER (positive vs. negative), PR (positive vs. negative), HER2 (positive vs. negative), LVI (present vs. absent) and TILs (high vs. intermediate vs. low)
  4. bTILs were categorised as low: < 10%, intermediate: 10–49% and high: ≥ 50%
  5. cA series of multivariable analyses including TILs and only one additional prognostic variable at a time revealed that the univariable effect of intermediate vs. low TILs on outcome was mainly confounded by NHG. In the prognostic cohort, 65% of the patients with intermediate TILs had NHG 3 tumours