POTENTIAL OFCIRCULATING CHEMOKINES AS SERUM

TUMOUR MARKERS IN BREAST CANCER

M. Costello, Marion Hartmann, R.M. Dwyer and M.J. Kerin

Department of Surgery, National University of Ireland Galway, Ireland

Tumour markers in breast cancer

Despite improvement in detection and treatment breast cancer remains leading cause of female cancer related death world wide

Circulating serum markers e.g. CA 15-3 have been shown to play a role in prognosis, management and monitoring of breast cancer

However, there is an urgent need for more specific and reliable markers

CCL5/RANTES (Regulated upon Activation, Normal T cell Expressed and presumably Secreted) 8kDa chemotactic cytokine with a principal role in the inflammatory

response Conflicting reports relating to potential role of CCL5 in breast cancer

progression

Transforming Growth Factor Beta 1 (TGF-β1) Pleiotropic cytokine with a well established role in carcinogenesis Thought to act as a tumour suppressor in early stage breast cancer and

potentially promote tumourigenesis as the disease progresses

CCL5 and TGF-β1 in breast cancer

Aim

Investigation of circulating levels of TGF-β1 and CCL5 in breast cancer patients and correlation of results with clinicopathological

characteristics

MethodsStudy group N

Breast Cancer Patients 110

Age matched controls 69

Preoperative serum samples and controls were measured using ELISA (enzyme linked immunosorbent assay)

Circulating CCL5

Control (n=69)Breast cancer (n=110)

250

200

150

100

50

0

CC

L5

(ng/

ml)

Circulating CCL5 levels in breast cancer patients compared to control

* = outliers

∆ p< 0.01

∆∆

Relationship between circulating CCL5 levels and epithelial subtypes

Basal (n=10)Her2 (n= 4)Luminal B (n=11)Luminal A (n= 70)

250

200

150

100

50

0

CC

L5

( ng

/m

l )

Epithelial Subtype

∆∆

Relationship between circulating CCL5 levels and epithelial subtype

* = outliers

∆ p<0.01

2 5 0

2 0 0

1 5 0

1 0 0

5 0

0

C C L 5 a n d l y m p h n o d e s t a t u s

0n=49

≤2n=19

3-9n=15

≥10n=8

CCL5

(ng/

mL)

Number of Lymph Nodes positive

2 5 0

2 0 0

1 5 0

1 0 0

5 0

0

C C L 5 a n d l y m p h n o d e s t a t u s

0n=49

≤2n=19

3-9n=15

≥10n=8

CCL5

(ng/

mL)

Number of Lymph Nodes positive

∆ ∆□□

* = outliers□ ∆ p< 0.05

Results TGF-β1

Levels were found to be significantly higher in breast cancer patients than the control group (p<0.05)

∆

∆

Controls (n=37)Breast Cancer Patients (n=94)

90

80

70

60

50

40

30

20

10

0

TGF-

ß1 n

g/m

L

Ci rcula t i ng TGF-ß1 levels i n Breas t Cancer pa t ients compared to cont rol

* = outliers∆ p < 0.05

∆

∆

* = outliers□ ∆ p< 0.05

∆□

∆ □

>2 nodes positive (n=31)≤ 2 nodes positive (n=12)Node Negative(n=36)

90

80

70

60

50

40

30

20

10

0

TGFß

1 ng

/mL

Ci rculating TGF-ß1 levels and axi l lary node status

number of lymph nodes positive* = outliers□ ∆ p< 0.05* = outliers□ ∆ p< 0.05

∆ □

□∆

Significant positive Pearson correlation between circulating CCL5 and TGFβ1

0

50

100

150

200

250

300

serum samples (n=138) R=0.44 P<0.0001

CC

L5

/TG

Fβ

1 (

ng

/ml) CCL5

TGFβ 1

Summary No significant difference between CCL5 levels in breast cancer

patients while TGF-β1 levels were significantly higher

Significant higher serum levels of CCL5 found in patients with more invasive Basal subtype than Luminal A subtype

There was a significant increase in CCL5 and TGF-β1 levels as nodal involvement increased

Conclusion

CCL5 plays a potential role in breast cancer metastasis. A significant positive correlation between CCL5 and TGF-β1 across all samples examined suggests potential synergistic

effect between the two factors that warrants further investigation.