Detection of circulating tumour cells in breast cancer patients using human mammaglobin RT-PCR: association with clinical prognostic factors

Abstract

Background: So far discordant results regarding the significance of tumour cells circulating in peripheral blood (CTCs) of breast cancer (BC) patients have been reported. Our aim was to evaluate the association of indirect CTC detection by amplification of human mammaglobin (hMAM) gene expression with traditional prognostic markers of clinical outcome in BC at the time of diagnosis.

Patients and methods: Peripheral blood samples from 190 patients with invasive and 12 patients with in situ BC, before therapy and/or surgery, from 184 patients with benign breast disease and from 146 healthy volunteers were tested for hMAM expression by a nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Correlations between CTCs and age at diagnosis, tumour type and size, grading, lymph node involvement, oestrogen and progesterone receptor status, HER-2/neu expression and Ki-67/MIB-1 labelling index were assessed through the odds ratio (OR) point estimates, considering OR >2.0 or <0.5 as being clinically relevant. ORs and their corresponding 95% confidence limits (95% CL) were obtained by logistic regression analysis.

Results: Expression of hMAM was found only in peripheral blood of patients with invasive BC (9.5%) and multivariate logistic regression analysis indicated its association with lymph node involvement (pN1-pN3 vs. pN0, OR=5.6, 95% CL=1.4-22.6; p=0.009), tumour size (pT2-pT4 vs. pT1, OR=2.3, 95% CL=0.6-9.0; p=0.207) and negative ER status (OR=2.5, 95% CL=0.6-10.0; p=0.227).

Conclusion: Our data show that CTC detection in invasive BC at the time of diagnosis is associated with poor prognosis and may also be used as an additional prognostic indicator.