Prognostic relevance of induced and spontaneous apoptosis of disseminated tumor cells in primary breast cancer patients

Abstract

BackgroundAn imbalance between cell proliferation and programmed cell death can result in tumor growth. Although most systemic cytotoxic agents induce apoptosis in tumor cells, a high apoptotic rate in primary breast cancer correlates with poor prognosis. The aim of this study was to investigate the incidence and the prognostic significance of apoptotic disseminated tumor cells (DTC) in the bone marrow (BM) of breast cancer patients who either underwent primary surgery or primary systemic chemotherapy (PST).MethodsA total of 383 primary breast cancer patients with viable DTC in the BM were included into this study. Eighty-five patients were initially treated with primary systemic chemotherapy whereas 298 patients underwent surgery first. Detection of apoptotic DTC were performed by immunocytochemistry using the M30 antibody which detects a neo-epitope expressed after caspase cleavage of cytokeratin 18 during early apoptosis. The median follow up was 44 months (range 10–88 months).ResultsEighty-two of 298 (27%) primary operated patients and 41 of 85 (48%) patients treated with primary systemic systemic therapy had additional apoptotic DTC (M30 positive). In the neoadjuvant group M30-positive patients were less likely to suffer relapse than those without apoptotic DTC (7% vs. 23% of the events, p = 0.049). In contrast, the detection of apoptotic DTC in patients treated by primary surgery was significantly associated with poor overall survival (5% vs. 12% of the events, p = 0.008).ConclusionsApoptotic DTC can be detected in breast cancer patients before and after systemic treatment. The presence of apoptotic DTC in patients with PST may be induced by the cytotoxic agents. Thus, both spontaneous and chemotherapy-induced apoptosis may have different prognostic significance.

Changes in Cytokeratin 18 during Neoadjuvant Chemotherapy of Breast Cancer: A Prospective Study

“…However, there was no significant difference in serum levels of this marker based on hormone receptor or other tumor characteristics (9). The results of Tas et al, Demiray et al and this study are however inconsistent with the findings of a research by Krawczyk et al, where the incidence of M30 in breast tumor tissue was investigated by immunohistochemistry and the results showed higher incidence of this cytokeratin in hormone-positive and HER2-positive subtypes and cancers with lower grade tumors (23). The results of the present study showed no significant relationship between changes in M30, M65 and M30/M65 ratio during chemotherapy and survival parameters.…”

Significance of apoptotic and non‐apoptotic disseminated tumor cells in the bone marrow of patients with clinically localized prostate cancer

“…Our study is the first assessing the prognostic value of markers of apoptosis in DTCs of PC patients. In contrast to studies in breast cancer, a further characterization of cytokeratine positive DTCs into apoptotic and non‐apoptotic cells did not add any additional prognostic information to conventional pancytokeratine staining .…”

Cut-Off Analysis of CTC Change under Systemic Therapy for Defining Early Therapy Response in Metastatic Breast Cancer

“…Regarding the optimized aCTC cut-off, >50% reduction (n = <50% reduction (n = 49) showed a median PFS of 6 (5-10) vs. 3 (3-5) months (p = 0.0085) and a OS of 24 (17-34) vs. 10 (7-16) months (p < 0.0001). Regarding the optimized iCTC+aCTC >66.7% reduction (n = 57) vs. <66.7% reduction (n = 51) showed a median PFS of 6 (5-10) vs. months (p = 0.0063) and a median OS of 24 [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] vs. 10 (7-15) months (p = 0.0025). The impact of the optimized cut-offs on OS and PFS is shown in Figure 3.…”

“…In 52-79% of CTC-positive MBC patients, aCTCs have been observed in peripheral blood samples [17][18][19]. They are thought to be a product of therapy-induced and/or spontaneous apoptosis [20,21]. Whatever the cause of apoptosis may be, significantly higher aCTC counts were detected in patients with MBC than in those with early breast cancer [22].…”