Prognostic Value of Cytokeratin 19 Fragment (CYFRA 21–1) and Cytokeratin-Positive Cells in Bone Marrow Samples of Breast Cancer Patients

2004 ◽  
Vol 19 (1) ◽  
pp. 23-31
Author(s):  
J.-Y. Pierga ◽  
L. Deneux ◽  
C. Bonneton ◽  
A. Vincent-Salomon ◽  
C. Nos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Clinical Stage ◽  
Univariate Analysis ◽  
Bone Marrow Aspiration ◽  
Cytokeratin 19 ◽  
Cell Detection ◽  
Breast Cancer Patients ◽  
Primary Tumors

The aim of this study was to investigate the relationship between the detection of micrometastatic cells by immunocytochemistry (ICC) with an anticytokeratin antibody and cytokeratin fragment (CYFRA 21–1) expression detected by an immunofluorescent assay in bone marrow of breast cancer patients. Micrometastatic CK+ cells were screened with a pancytokeratin antibody A45 B/B3 from bone marrow aspiration samples of 102 breast cancer patients (65 primary tumors, 10 local recurrences and 27 distant metastases). CYFRA 21-1 levels were assessed in bone marrow supernatant of these patients before collection of the mononucleated interface cells on a Ficoll-Hypaque density gradient and in 20 control patients. CYFRA 21-1 and CK+ cell detection by ICC were both correlated with clinical stage. CYFRA 21-1 was significantly elevated in patients with micrometastatic disease detected by ICC: 4.77 ng/mL (± 10.87 SD) versus 1.00 ng/mL (± 1.36 SD) in patients with negative ICC (p=0.01). In univariate analysis, a CYFRA 21-1 value ≥1 ng/mL and the presence of CK+ cells were associated with a poorer survival for patients with stage I to III breast cancer (n=65). On multivariate analysis, only pathological nodal status and presence of CK+ cells in bone marrow were independent prognostic factors for overall survival. In conclusion, in this series CYFRA 21-1 was correlated with detection of CK+ cells by ICC in bone marrow, but cannot replace ICC. The presence of CK+ cells in bone marrow remains a strong independent prognostic factor in primary breast cancer.

Estrogen receptor (ER) status of disseminated tumor cells in the bone marrow of breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21013-21013
Author(s):  
F. N. Tanja ◽  
N. Krawczyk ◽  
D. Wallwiener ◽  
S. Becker ◽  
E. Solomayer
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Hormone Receptor ◽  
Primary Breast Cancer ◽  
Disseminated Tumor Cells ◽  
Breast Cancer Patients ◽  
Primary Tumors

21013 Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer patients is associated with poor prognosis. These patients may benefit from adjuvant endocrine therapy since cytotoxic agents are not able to completely eliminate DTCs as previously shown. Only patients with hormone receptor positive breast cancer are eligible for hormonal treatment. The ERa status is routinely defined in primary tumor tissue. However, the ERa status of DTC may differ compared to the primary tumor. Therefore, the aims of this study were (1) to determine the ERa status of DTC in BM of breast cancer patients, (2) and to compare the ERa status of DTC and corresponding primary tumors. Methods: BM aspirates from 251 primary breast cancer patients were included into the study. A double immunofluorescence staining procedure was established for the identification of cytokeratin-positive (CK)/ERa positive cells. ERa status of the primary tumor was immunohistochemically assessed using the same antibody against ERa. Results: In 105 of 251 (42%) breast cancer patients CK-positive cells could be detected in BM. The number of detected cells ranged between 1 and 13 / cells per 2*106 mononuclear cells. Disseminated tumor cells demonstrated ERa positivity in 13 (12%) of these 105 patients. The ERa expression on DTC was heterogeneous in 10 of 13 (79%) patients. Concordance rate of ERa status between primary tumor and DTC was 27%. Only 11 of 83 patients with ER a positive tumors had also ERa positives DTC. Conclusions: (1)The hormone receptor status between primary tumor and corresponding DTC is disconcordant. (2)This discrepancy may explain the rate of non-responders to adjuvant endocrine therapy despite ER-positive primary tumors. (3)These patients may benefit from adjuvant therapy regimens based on antibody strategies or bisphosphonates. No significant financial relationships to disclose.

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

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
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.

Identification of patients at high risk of recurrent disease development by detection of HER2-positive disseminated tumor cells in bone marrow of patients with HER2-negative tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 633-633
Author(s):  
Rebecca Aft ◽  
Chidananda Mudalagiriyappa ◽  
Sreeraj Pillai ◽  
Kathryn Trinkaus ◽  
Timothy Fleming ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Disseminated Tumor Cells ◽  
Stage Ii ◽  
Her2 Expression ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Primary Tumors

633 Background: A subpopulation of patients with HER2-negative tumors benefit from HER2 therapy. HER2 expression can be discordant between primary tumors and metastases. We have examined the bone marrow (BM) of early stage breast cancer patients for HER2-expression by disseminated tumor cells (DTCs) and the association with disease recurrence. Methods: BM was collected from clinical stage II-III breast cancer prior to treatment between 2007-2011. Gene expression of ERBB2 was determined by multiplex PCR (Fluidigm Biomark [FB]). Positive expression was defined as at least 1.4 fold above a pool of normal BM. Expression was confirmed by single gene PCR and Nanostring nCounter (NC) assays. Cox proportional model was used to estimate hazard ratios (HR). Results: BM from 74 patients was analyzed. Median follow-up was 3.4 years (range 8 months-84 months). 24% of the patients developed metastatic disease. For ERBB2 detection, there was excellent correlation between NC and the FB assays (kappa=0.87, 95% CI [0.62, 1.00]). Nine patients expressed ERBB2 in their BM. Five of the 9 patients had Her2-positive tumors and were treated with trastuzumab. One of 5 (20%) of these patients relapsed whereas 75% (3 of 4) of the patients with HER2-negative tumors but ERBB2-positive DTCs relapsed. Patients with HER2-negative tumors/ERBB2-positive BM were found to have a greater hazard of recurrence than patients with HER2-negative tumors/ERBB2-negative BM or ERBB2-positive DTCs treated with trastuzumab (p=.0069; Table). Those patients with ERBB2-positive BM who did not receive trastuzumab had a decreased disease free survival (p=.016). Conclusions: We have found discordant expression of HER2/ERBB2 in tumors and BM of stage II-III breast cancer patients. The presence of ERBB2 expressing DTCs in patients with HER2-negative tumors identifies a subset of patients at increased risk of recurrence who may benefit from targeted HER2-therapy. [Table: see text] .

Analysis of disseminated tumor cells (DTCs) in primary breast cancer patients with various molecular subtypes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13000-e13000
Author(s):  
Ivonne Nel ◽  
Laura Weydandt ◽  
Annekathrin Höhn ◽  
Bahriye Aktas
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Primary Breast Cancer ◽  
Molecular Subtypes ◽  
Immunocytochemical Staining ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Primary Tumors ◽  
Luminal B

e13000 Background: Despite successful treatment of the primary tumor, recurrence occurs in about 30% of breast cancer patients. One reason might be hematogenous spread during early disease stages. Disseminated breast cancer cells (DTCs) preferentially migrate into the bone marrow (BM) at early stages of the disease. Due to low proliferation, DTCs are persistent against systemic chemotherapy and might cause metastatic relapse at a later stage. Methods: BM aspirates were collected from the anterior iliac crest of patients with primary mamma carcinoma during surgery. After density gradient centrifugation cell suspensions were transferred onto glass slides and subjected to immunocytochemical staining against pan-cytokeratin. DTCs were visualized in pink using alkaline phosphatase and short counterstaining with hematoxylin which colored the nuclei light blue. DTCs were semi-automatically detected and enumerated using the Aperio Versa microscope based scanning system with a rare events algorithm that was trained to identify DTC candidates according to color, shape, intensity and size. As a positive control with each run, we used reference slides with a mix of bone marrow cells and a defined number of HCT116 cells. Results: Between February 2019 and December 2020 BM aspirates from 158 primary breast cancer patients were collected. Per patient about 4 million BM cells were analyzed. DTC detection revealed a positivity rate of 29% (46 patients). Molecular subtype analysis of DTC positive patients showed that 37% of the primary tumors (17 patients) were luminal A and 37% (17 patients) luminal B. In 9% of the cases (4 patients), tumors were HER2 enriched and 15% (8 patients) were triple negative. DTC count indicated that the majority of luminal B patients had 11-20 DTCs whereas luminal A patients tended to have lower DTC quantities varying between 1 and 10 DTCs. Conclusions: DTCs may serve as independent prognostic markers. Follow-Up data might reveal whether DTC quantification and molecular subtypes at primary diagnosis can be used to stratify patients at elevated risk for recurrence.

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