Abstract

Background

Many different factors are involved in tumour invasion and metastasis. Human mammaglobin-A is specifically expressed in breast tissue, over-expressed in some breast cancers and has been associated with less aggressive phenotypes. Vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are involved in the development and growth of vascular and lymphatic endothelia. However, the relevance of plasma levels of these factors in breast cancer remains unclear.

Method

Paired pre- and post-operative plasma samples from 80 patients undergoing breast surgery (benign or breast cancer) were analysed by ELISA for mammaglobin-A, VEGF and PlGF levels. Plasma levels were correlated with tumour pathology (Spearman’s correlation coefficient). Patients were followed up for a minimum of 8 years and disease-free and overall survival analysis was performed (Kaplan Meier, p<0.05). The study had research ethics approval.

Results

The median (range) observed plasma levels for each factor were:

Plasma Levels

Median (range)

Mammaglobin-A

(ng/ml)

VEGF

(pg/ml)

PlGF

(pg/ml)

Pre-op plasma

0.81 (0-10.1)

55.3 (2.7-275.1)

8.5 (1.4-19.1)

Post-op plasma

1.2 (0.2-8.5) *

60.1 (0-521.4)

8.9 (2.5-28.2)

* p<0.05 Wilcoxon

There was no association between plasma levels with tumour grade or metastasis, however pre- and post-operative VEGF levels were lower in benign samples than tumour samples..

At follow up; 50 patients were alive and well, 8 were alive but with cancer and 11 patients had died (8 were cancer related). The remaining 11 patients were lost to follow-up.

With overall survival, higher pre-operative plasma levels of all three factors were associated with poorer survival outcome. Higher post-operative plasma levels of VEGF and pre-operative levels of PlGF were also associated with poorer disease free survival.

Conclusion

Differential plasma levels of mammaglobin-A, VEGF and PlGF were observed with tumour pathology and survival. In a larger sample, pre-operative plasma levels of these factors may help predict overall and disease-free survival.