Cytokeratin-19 mRNA-positive circulating tumor cells during follow-up of patients with operable breast cancer: prognostic relevance for late relapse

Abstract

BackgroundThe detection of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTC) before and/or after adjuvant chemotherapy in patients with operable breast cancer is associated with poor clinical outcome. Reliable prognostic markers for late disease relapse are not available. In this study we investigated the value of CTC detection during the first five years of follow-up in predicting late disease relapse.MethodsBlood was analyzed from 312 women with operable breast cancer who had not experienced disease relapse during the first two years of follow-up. A real-time reverse transcriptase polymerase chain reaction (RT-PCR) for CK-19 mRNA was used to detect CTC three months after the completion of adjuvant chemotherapy and every six months thereafter for a follow-up period of five years.ResultsEighty patients (25.6% of the study population) remained CTC free throughout the five-year period. A change in CTC status was observed in 133 patients (42.6%); 64 patients (20.5%) with initially CK-19 mRNA-positive CTC during the first 24 months turned CTC-negative afterwards while 69 (22.1%) who were initially CTC-negative became CTC-positive. Ninety-nine patients (31.7%) remained persistently CK-19 mRNA-positive. After a median follow-up period of 107 months (range: 38 to 161 months), the persistently CTC-positive patients with either hormonal receptor positive or negative tumors, had a higher risk of late-disease relapse compared to the persistently CTC-negative patients (36.4% versus 11.2%, P <0.001). Multivariate analysis revealed that persistently CTC-positive patients also had a shorter disease-free (P = 0.001) and overall survival (P = 0.001).ConclusionsPersistent detection of CK-19 mRNA-positive CTC during the first five years of follow-up is associated with an increased risk of late relapse and death in patients with operable breast cancer and indicates the presence of chemo-and hormonotherapy-resistant residual disease. This prognostic evaluation may be useful when deciding on subsequent adjuvant systemic therapy.

Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer

“…Among the highly expressed genes in CTCs, 27 (33.8%) and 25 (31.3%) patients expressed TFF1 and mammaglobin, respectively. In addition, the keratin 19 (KRT19) gene was highly correlated with the CTC count, consistent with previously reported findings (10). The scatter plot of the correlation between KRT19 and the rank order Also referred to as mammary serine protease inhibitor (maspin).…”

PIK3CA Mutational Status in Circulating Tumor Cells Can Change During Disease Recurrence or Progression in Patients with Breast Cancer

“…8). Persistent detection of CTCs during the first 5 years of follow-up was associated with an increased risk of late disease relapse and death and indicates the presence of chemo-and hormone therapy-resistant residual disease (9), whereas a recent prospective clinical study confirmed that the presence of one or more CTCs predicted for early recurrence and decreased OS (10).…”

Predictive Factors for Late (>5 Years) Distant Recurrences in Hormone Receptor (HR) Positive, Human Epidermal Growth Factor Receptor 2 (HER2) Negative Breast Cancer Patients: >20 Year Follow Up

“…This study showed that enrichment in genes involved in immune response may play a role in suppressing anti-tumoral immunity enabling the dormant tumor cells to re-enter the cell cycle to form metastases [25]. Another study identified that the persistence of circulating tumor cells (after completion of adjuvant chemotherapy) in patients with either hormonal receptor positive or negative tumors, is also associated with a higher risk of late-disease relapse compared to those who were negative for persistently circulating tumor cells (36.4% vs. 11.2%, P<0.001) [26][27][28][29].…”