Table 3

GRADE summary of findings

HR for OS and DFS
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
Participants, n
(studies)
Quality of evidence
(GRADE)
Comments
Assumed riskCorresponding risk
ControlHR
OS: histopathology and follow-up visit.
Scale from 0 to 10.
Follow-up: 10 years.
The mean OS ranged across control groups from
10 years.
The mean OS in the intervention groups was
1.77 SD higher
(1.4 to 2.23 higher).
6878
(18 studies)
⊕⊕⊕⊕
High†‡
DFS: histopathology and follow-up visit.
Scale from 0 to 10.
Follow-up: 10 years.
The mean DFS ranged across control groups from
10 years.
The mean DFS in the intervention groups was
1.82 SD higher
(1.56 to 2.13 higher).
2137
(11 studies)
⊕⊕⊕⊕
High†‡
Clinical pathological information
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
Participants, n
(studies)
Quality of evidence
(GRADE)
Comments
Assumed riskCorresponding risk
ControlClinical pathological information
Histological grade 3: histopathology files and patient informationStudy populationOR 3.51
(3.05 to 4.04)
4631
(17 studies)
⊕⊕⊕⊝
Moderate†
305 per 1000606 per 1000
(572 to 639)
Moderate
287 per 1000586 per 1000
(551 to 619)
High T - T3/4: histopathology files and patient informationStudy populationOR 0.95
(0.71 to 1.26)
2398
(7 studies)
⊕⊕⊝⊝
Low
132 per 1000126 per 1000
(97 to 160)
Moderate
120 per 1000115 per 1000
(88 to 147)
Lymph node metastasis: histopathology files and patient informationStudy populationOR 1.48
(1.29 to 1.7)
3954
(14 studies)
⊕⊕⊕⊝
Moderate†
424 per 1000522 per 1000
(487 to 556)
Moderate
418 per 1000515 per 1000
(481 to 550)
Clinical stage III/IV: histopathology files and patient informationStudy populationOR 1.26
(0.8 to 1.97)
405
(3 studies)
⊕⊕⊝⊝
Low
226 per 1000269 per 1000
(189 to 365)
Moderate
221 per 1000263 per 1000
(185 to 359)
Molecular subtype
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
Participants, n
(studies)
Quality of evidence
(GRADE)
Comments
Assumed riskCorresponding risk
ControlMolecular subtype
Luminal A: histopathology files and patient informationStudy populationOR 0.3
(0.26 to 0.34)
5873
(7 studies)
⊕⊕⊕⊝
Moderate§
526 per 1000250 per 1000
(224 to 274)
Moderate
597 per 1000308 per 1000
(278 to 335)
Luminal B: histopathology files and patient informationStudy populationOR 0.7
(0.6 to 0.81)
5877
(7 studies)
⊕⊕⊕⊝
Moderate§
226 per 1000169 per 1000
(149 to 191)
Moderate
175 per 1000129 per 1000
(113 to 147)
HER2(+) subtypes: histopathology files and patient informationStudy populationOR 3.01
(2.51 to 3.61)
6094
(9 studies)
⊕⊕⊕⊝
Moderate†
58 per 1000157 per 1000
(134 to 182)
Moderate
79 per 1000205 per 1000
(177 to 236)
Triple-negative or basal-like type: histopathology files and patient informationStudy populationOR 4.97
(4.31 to 5.72)
7555
(10 studies)
⊕⊕⊕⊝
Moderate†
71 per 1000276 per 1000
(249 to 305)
Moderate
85 per 1000316 per 1000
(286 to 347)
Molecular phenotype
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
Participants, n
(studies)
Quality of evidence
(GRADE)
Comments
Assumed riskCorresponding risk
ControlMolecular phenotype
ER-positive: histopathology filesStudy populationOR 0.28
(0.25 to 0.31)
7640
(15 studies)
⊕⊕⊕⊝
Moderate§
720 per 1000419 per 1000
(391 to 444)
Moderate
714 per 1000411 per 1000
(384 to 436)
PR-positive: histopathology filesStudy populationOR 0.39
(0.35 to 0.44)
6930
(11 studies)
⊕⊕⊕⊝
Moderate§
453 per 1000244 per 1000
(225 to 267)
Moderate
585 per 1000355 per 1000
(330 to 383)
HER2-positive: histopathology filesStudy populationOR 2.47
(1.93 to 3.16)
7169
(12 studies)
⊕⊕⊕⊝
Moderate†
116 per 1000245 per 1000
(203 to 294)
Moderate
155 per 1000312 per 1000
(261 to 367)
Ki-67-positive: histopathology filesStudy populationOR 2.52
(2.24 to 2.83)
5422
(6 studies)
⊕⊕⊕⊝
Moderate†
327 per 1000550 per 1000
(521 to 579)
Moderate
329 per 1000553 per 1000
(523 to 581)
EGFR-positive: histopathology filesStudy populationOR 5.85
(4.46 to 7.68)
5600
(4 studies)
⊕⊕⊕⊕
High¶
21 per 1000114 per 1000
(89 to 144)
Moderate
21 per 1000111 per 1000
(87 to 141)
Cytokeratin 5/6 positive: histopathology filesStudy populationOR 7.51
(6.08 to 9.28)
5863
(6 studies)
⊕⊕⊕⊕
High¶
39 per 1000235 per 1000
(199 to 275)
Moderate
89 per 1000423 per 1000
(373 to 476)
  • GRADE Working Group grades of evidence: High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate. GRADE, Grading of Recommendations Assessment, Development and Evaluation.

  • ⊕ Upgrade 1 level. ⊝ Downgrade 1 level.

  • *The basis for the assumed risk (eg, the median control group risk across studies) is provided. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

  • †RR >2 based on consistent evidence from at least two studies with no plausible confounders.

  • ‡Immunohistochemical staining was used to evaluate P-cadherin expression in all the included studies. A possible bias of 1 is associated with different cut-off values of P-cadherin staining in tumour cells. For most studies, P-cadherin staining of 5% or more tumour cells was considered to be positive tumour expression. However, for some studies which had a greater weight among all included studies, P-cadherin staining of 50% or more tumour cells was considered as positive tumour expression. We observed that when the cut-off value was higher (>10%), the HR value of OS and DFS were lower, which could affect the outcome. The confidence is still large in this effect and may lead to upgrading by one level.

  • §RR <0.5 based on consistent evidence from at least two studies with no plausible confounders.

  • ¶RR >5.0 based on direct evidence with no major threats to validity.

  • DFS, disease-free survival; EGFR, epidermal growth factor receptor; ER, oestrogen receptor; HER2, human epidermal growth factor receptor-2; OS, overall survival; PR, progesterone receptor.