A small subgroup of operable breast cancer patients with poor prognosis identified by quantitative real-time RT-PCR detection of mammaglobin A and trefoil factor 1 mRNA expression in bone marrow

e12104 Background: Circulating tumor cells (CTCs) have proven to be underlying surrogate markers for several cancers. We aimed to investigate the diagnostic, predictive, and prognostic value of tCTCs using a four-CTC marker (CK19, surviving, Her2 and MUC1) real-time quantitative PCR (RT-PCR) assay in patients with breast cancer. Methods: In a previous study, we established a multimarker RT-PCR platform to detect and quantify CTC in colorectal cancer. By choosing four mRNA markers (CK-19/surviving/Her2/Muc1), we quantified CTC in the peripheral blood of 90 early operable breast cancer patients, 40 patients who had undergone surgery and received 6 cycles of follow-up of neoadjuvant chemotherapy, and 30 healthy volunteers. For early operable breast cancer patients, the CTC status at preoperative and postoperative time points was monitored. For the other 40 patients undergoing systemic adjuvant chemotherapy, the CTC status at six or more different time points was monitored. Results: CTCs were detected in 81% (73/90) of patients with early operable breast cancer. After surgery, 67.1% (49/73) of the patients switched to negative status. 36 out of 40 (90%) patients who received systemic adjuvant chemotherapy were CTC-positive. During follow-up, 31 out of 36 (86%,) patients became CTC-negative after 4 chemotherapy cycles. Among these 36 patients, four patients had relapsed within one year, and one had died. Three out of four relapsed patients, including the deceased one, switched into high CTC-positive status before diagnosed recurrence. Conclusions: The decrease of the levels of these CTC mRNA markers after surgery indicates that these CTC markers could be used as an indirect evaluation of tumor burden. The level of CTC mRNA markers could also help to evaluate therapeutic efficacy and disease progression.

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Detection of disseminated tumor cells in bone marrow predict late recurrences in operable breast cancer patients

BMC Cancer ◽

10.1186/s12885-019-6268-y ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Kjersti Tjensvoll ◽

Oddmund Nordgård ◽

Maren Skjæveland ◽

Satu Oltedal ◽

Emiel A. M. Janssen ◽

...

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Cancer Patients ◽

Tumor Cells ◽

Cox Regression ◽

Disseminated Tumor Cells ◽

Operable Breast Cancer ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Post Surgery

Abstract Background Operable breast cancer patients may experience late recurrences because of reactivation of dormant tumor cells within the bone marrow (BM). Identification of patients who would benefit from extended therapy is therefore needed. Methods BM samples obtained pre- and post-surgery were previously analysed for presence of disseminated tumor cells (DTC) by a multimarker mRNA quantitative reverse-transcription PCR assay. Updated survival analyses were performed on all patient data (n = 191) and in a subgroup of patients alive and recurrence-free after 5 years (n = 156). DTC data were compared to the mitotic activity index (MAI) of the primary tumors. Median follow-up time was 15.3 years. Results Among the 191 patients, 49 (25.65%) experienced systemic relapse, 24 (49%) within 5–18 years after surgery. MAI and pre- and post-operative DTC status had significant prognostic value based on Kaplan–Meier analyses and multiple Cox regression in the overall patient cohort. With exclusion of patients who relapsed or died within 5 years from surgery, only pre-operative DTC detection was an independent prognostic marker of late recurrences. High MAI (≥10) did not predict late recurrences or disease-specific mortality. Conclusion Pre-operative DTC detection, but not MAI status, predicts late recurrences in operable breast cancer.

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