Table 2 Summary of the candidate biomarkers detected in different studies

Number

134

169

176

89

96

16 cancer pre- and post-surgery samples

62

310

114

95

65

60

6

45 patients with breast cancer, 42 benign disease, 47 healthy controls

99 stage I–III

61 patients locally invasive breast cancers (IBC), 32 DCIS, 37 benign breast lesions (19 atypical ductal hyperplasia (ADH)), 46 age-matched healthy subject

49 patients with breast cancer, 13 patients with benign breast disease, 27 from healthy controls

48 primary invasive breast cancer vs. 48 healthy

15 healthy

15 BRCA1 cancer

155 patients with stage I invasive ductal carcinoma (IDC) of the breast 155 healthy controls

81 benign diagnosis, 6 ADH, 5 DCIS, and 22 invasive breast cancer (IBC)

21 cancer

4 DCIS

15 BRCA1 carrier

44 healthy

41 healthy controls

16 SBC

25 benign disease

16 Norml

Sample

Serum

Serum

Serum

Serum

Serum

Serum

Serum

Serum

NAF

NAF and ductal lavage fluid

NAF

Cytosol

Saliva

Array used

IMAC30, Q10

IMAC-Ni

IMAC-Ni

IMAC-Ni

IMAC-Ni

IMAC-Cu

IMAC-Cu

IMAC-Cu

H4, NP and Q10

IMAC30

IMAC30

IMAC-Cu, Q10

CM10

Differential peaks

Cancer vs. control

BC1: 4.3 kDa↓ ^a

BC2: 8.1 kDa ↑ ^a

BC1: 4.3 kDa ↓ ^a

Cancer vs. control

Pre- vs. post-surgery

BRCA1 cancer vs. carrier

5.99255 kDa ↓ ^a

Cancer vs. healthy NAF: 5.2, 11.9, and 13.9 kDa

3.38 kDa

Breast cancer vs. healthy: 6.5, 8.0, 15.9, 28.1, and 31.8 kDa

8.5 kDa IMAC30 (ubiquitin)

18.113 kDa

 2.95 kDa

BC2: 8.1 kDa ↑ ^a

BC3: 8.9 kDa ↑ ^a

BC1a: 4.286 kDa ↓ ^a

 BC1: 4.3 kDa ↓^a

 6.194 kDa↑

8.138 kDa ↑ ^a

5.83850 kDa ↓

DCIS vs. benign disease differentially expressed peaks: 5.2 and 33.4 kDa

Ipsilateral affected breast vs. healthy breast

19.8 kDa SAX

170 kDa

 3.68 kDa

BC3: 8.9 kDa ↑ ^a

BC1b: 4.302 kDa ↓ ^a

 BC3: 8.9 kDa ↓^a

 2.276 kDa ↑

5.909 kDa ↓ ^a

2.95470 kDa ↓

ADH vs. benign disease: 5.2 kDa

3.45 kDa

 CM10: 3.471 , 3.511, 4.151, 4.586, 4.646, 4.698 kDa

(Ferritin light chain) FLC

228 kDa

 4.27 kDa

BC3: 8.9 kDa ↑ ^a

 3.892 kDa ↑

BRCA1 cancer vs. SBC

5.88770 kDa ↓

Breast cancer vs. benign lesion: 13.9 kDa

3.49 kDa

 IMAC30: 3.501, 3.627, 4.147 kDa

287 kDa

Cancer vs. benign

BC3a: 8.919 kDa ↑ ^a

BRCA1 cancer vs. carrier

8.1 kDa ↑ ^a

9.01770 kDa ↑

Contralateral breast vs. healthy breast

 6.43 kDa

BC3b: 8.961 kDa ↑ ^a

 5.9 kDa ↓^a

8.65720 kDa ↑

 CM10: 3.471, 3.869, 4.151, 4.646, 14.720 kDa

 7.48 kDa

SLN + ve vs. SLN −ve

8.95650 kDa ↑ ^a

 IMAC30: 3.501, 3.627, 4.417, 4.376, 5.890 kDa

 8.61 kDa

SAX: 5.9065 ↓^a 4.0277, 7.4144 kDa

IMAC-Cu: 1.437, 1.003, 1.349 kDa

Comments

Using combination of peaks from two different chips improved sensitivity and specificity of detection to 90 and 93% respectively

BC1, BC2, and BC3 were suggested as potential breast cancer biomarkers. They achieved sensitivity and specificity of 93% and 91%, respectively

The study failed to validate BC1: 4.3 kDa

Failed to recover BC2: 8.1 kDa from Li et al. [16]

The study detected a possible BC2 peak at 8.1 kDa which was not differentially expressed between the two groups

All three differentially expressed peaks are overexpressed post-surgery

BRCA1 carriers and healthy had similar profiles

These 7 peaks were validated and tested to differentiate stage I breast cancer from healthy samples, and had strong sensitivity and specificity

Strongest peak was the 15.94 kDa identified as the β chain of hemoglobin

Identified as human neutrophils peptides (HNP) 1–3

No differentially expressed peaks were detected comparing the affected and contralateral breast NAF in the breast cancer group, which might suggest systemic changes in women with breast cancer

Combining St Gallen score to the 2 peaks led to strong prediction of none elapsing group (p < 0.0001) which could mean avoiding chemotherapy over treatment in 40% of breast cancer patients post-surgery

This small pilot study managed for the first time to detect significant proteomic peaks that differentiated DCIS from healthy subjects in human saliva

BC2 and BC3 were identified as complement components

No correlation was found between the markers and age, nodal status, metastasis, vascular invasion, ER/PR status, or Ca 15.3

No correlation between any candidate biomarker and tumor characteristics

5 peaks were retained by cancer patients post-treatment, whether this correlates to residual disease, poorer response/outcome, or DFS is yet to be studied

BRCA1 cancer had 8.1 kDa compared to BRCA1 carrier/SBC, but not from healthy patients

Interestingly, the same duplicate samples’ peaks were detected on the 3 chips in 90% of the runs

BC2 and BC3 did not correlate to size, grade, nodal, or ER/PR status

Addition to discrepancy in validation studies

Limited study—small sample size, needs validation

Peaks differentiated DCIS from benign disease, ADH and IBC