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Imaging, Diagnosis, Prognosis

HER2-Positive Circulating Tumor Cells Indicate Poor Clinical Outcome in Stage I to III Breast Cancer Patients

Pia Wülfing, Julia Borchard, Horst Buerger, Stefan Heidl, Kurt S. Zänker, Ludwig Kiesel and Burkhard Brandt
Pia Wülfing
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Julia Borchard
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Horst Buerger
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Stefan Heidl
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Kurt S. Zänker
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Ludwig Kiesel
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Burkhard Brandt
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DOI: 10.1158/1078-0432.CCR-05-2087 Published March 2006
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    Fig. 1.

    Survival curves of patients with primary breast cancer. Kaplan-Meier estimates for disease-free (A) and overall survival (B) with respect to presence and frequency of circulating HER2-positive tumor cells in the peripheral blood. The black dashed line represent patients in whom no HER2-positive tumor cell was detected. The gray curve shows survival of patients with circulating HER2-positive tumor cells.

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  • Table 1.

    Characteristics of patients examined for HER2-positive CTCs

    Clinicopathologic variablesn (%)
    Tumor stage*
        pT119 (55.9)
        pT29 (26.5)
        pT33 (8.8)
        pT43 (8.8)
    Lymph nodes*
        N025 (75.8)
        N+8 (24.2)
    Histologic grade
        G14 (11.8)
        G217 (50)
        G313 (38.2)
    Tumor type
        Ductal22 (62.9)
        Lobular9 (25.7)
        Tubular3 (8.6)
        Medullary1 (2.9)
    • ↵* Information on pT stage was available in 34 of 35 patients (97.1%) and information on pN stage was available in 33 of 35 (94.3%) patients.

  • Table 2.

    Identification and number of HER2-positive CTCs in stage I to III primary breast cancer patients (n = 35) and primary metastatic patients (M+, n = 7) as positive controls

    No. per samplePatients (%)
    Stage I-III patients
        018 (51.4)
        14 (11.4)
        22 (5.7)
        33 (8.6)
        43 (8.6)
        71 (2.9)
        84 (11.4)
        018 (51.4)
        1-412 (34.3)
        ≥55 (14.3)
        No18 (51.4)
        Yes17 (48.6)
    M+ patients (positive controls)
        3-507 (100)
  • Table 3.

    Correlation between presence of circulating HER2-positive tumor cells and clinicopathologic variables in primary breast cancer patients (n = 35)

    Clinicopathologic variablesPatients with HER2-positive CTCs, n/total (%)P*
    pT stage
        pT211/29 (37.9)0.006
        pT36/6 (100)
    Lymph node status
        Negative10/25 (40)NS
        Positive5/8 (62.5)
    Histologic grading
        I0/4 (0)0.033
        II-III17/30 (56.7)
    ER status
        Positive6/18 (33.3)0.039
        Negative11/16 (68.7)
    PR status
        Positive8/20 (40)NS
        Negative9/14 (64.3)
    HER2 status
        Negative12/24 (50)NS
        Positive2/3 (66.7)
    EGFR status
        Negative2/3 (14.3)NS
        Positive12/24 (50)
    MIB-1 labeling index
        20%8/19 (42.1)NS
        >20%8/12 (66.7)
    bcl-2 status
        Negative6/6 (100)NS
        Positive7/13 (53.8)
    p53 mutation
        No10/17 (58.8)NS
        Yes4/7 (71.4)
    • NOTE: Staining was evaluable for HER2 and EGFR in 27 (77.1%), for Ki-67(MIB-1 labeling index) in 31 (88.6%), for bcl-2 in 25 (71.4%), and for p53 in 24 (68.6%) of 35 patients with primary breast cancer.

      Abbreviation: NS, not significant.

    • ↵* χ2 test.

  • Table 4.

    Disease-free and overall survival in relationship to the detection of circulating HER2-positive tumor cells

    HER2-positive CTCsnDisease-free survival, mo (95% confidence interval)P*Overall survival, mo (95% confidence interval)P*
    No18124 ± 7 (110-139)0.007125 ± 7 (110-139)0.024
    Yes1760 ± 11 (38-83)89 ± 15 (60-117)
    018124 ± 7 (110-139)0.003125 ± 7 (110-139)0.021
    1-41272 ± 13 (46-97)80 ± 12 (57-103)
    ≥5532 ± 16 (1-62)61 ± 29 (4-118)
    • ↵* Log-rank test.

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Clinical Cancer Research: 12 (6)
March 2006
Volume 12, Issue 6
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HER2-Positive Circulating Tumor Cells Indicate Poor Clinical Outcome in Stage I to III Breast Cancer Patients
Pia Wülfing, Julia Borchard, Horst Buerger, Stefan Heidl, Kurt S. Zänker, Ludwig Kiesel and Burkhard Brandt
Clin Cancer Res March 15 2006 (12) (6) 1715-1720; DOI: 10.1158/1078-0432.CCR-05-2087

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HER2-Positive Circulating Tumor Cells Indicate Poor Clinical Outcome in Stage I to III Breast Cancer Patients
Pia Wülfing, Julia Borchard, Horst Buerger, Stefan Heidl, Kurt S. Zänker, Ludwig Kiesel and Burkhard Brandt
Clin Cancer Res March 15 2006 (12) (6) 1715-1720; DOI: 10.1158/1078-0432.CCR-05-2087
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