Original communication| Volume 135, ISSUE 4, P419-426, April 2004

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Persistent evidence of circulating tumor cells detected by means of RT-PCR for CEA mRNA predicts early relapse: A prospective study in node-negative breast cancer



      In 100 consecutive patients with node-negative breast cancer who underwent curative surgery, we prospectively tested whether detection of circulating tumor cells in peripheral blood by means of reverse transcription-polymerase chain reaction for carcinoembryonic antigen (CEA) messenger RNA (mRNA) could predict patient outcomes.


      We performed reverse transcription-polymerase chain reaction in blood samples taken before surgery and in repeat samples taken 2 to 3 weeks after surgery. Univariate and multivariate analyses of relapse-free survival were performed.


      Patients with CEA mRNA in preoperative samples had poorer survival rates than those who had no detectable CEA mRNA. The worst survival rate was seen in those with CEA mRNA in both pre- and postoperative samples. Stepwise multivariate analysis selected CEA mRNA expression pattern (P = .001; relative risk = 0.69) and histologic tumor grade (P = .002; relative risk = 1.35) as independent prognostic factors for disease-free survival.


      Molecular detection of CEA mRNA in both pre- and postoperative blood samples is an independent, negative prognostic factor in patients with node-negative breast cancer undergoing curative surgery.
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      1. National Cancer Institute of Health Consensus Development Panel: National Institute of Health Consensus Development Conference Statement: Adjuvant Therapy for Breast Cancer, November 1–3, 2000.
        J Natl Cancer Inst. 2001; 93: 979-989
        • Goldhirsh A
        • Glick J.H
        • Gelber R.D
        • et al.
        Meeting highlights: International Consensus Panel on the Treatment of Primary Breast Cancer.
        J Clin Oncol. 2001; 19: 3817-3827
        • Johnson P
        • Burchill S
        • Selby P
        The molecular detection of circulating tumour cells.
        Br J Cancer. 1995; 72: 268-276
        • Heyderman E
        • McCartney J.C
        Epithelial membrane antigen and lymphoid cells.
        Lancet. 1985; 1: 109
        • Smith B
        • Selby P
        • Southgate J
        • Pittman K
        • Bradley C
        • Blair G.E
        Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction.
        Lancet. 1991; 338: 1227-1229
        • Gerhard M
        • Juhl H
        • Kalthoff H
        • Schreiber H.W
        • Wagener C
        • Neumaier M
        Specific detection of carcinoembryonic antigen-expressing tumor cells in bone marrow aspirates by polymerase chain reaction.
        J Clin Oncol. 1994; 12: 725-729
        • Mori M
        • Mimori K
        • Ueo H
        • Karimine N
        • Barnard G.F
        • Sugimachi K
        Molecular detection of circulating solid carcinoma cells in the peripheral blood: the concept of early systemic disease.
        Int J Cancer. 1996; 68: 739-743
        • Fidler I
        The biology of human cancer metastasis.
        Acta Oncol. 1991; 30: 669-675
        • World Health Organization
        Histologic typing of breast tumours.
        in: International histologic classification of tumours, no. 2. World Health Organization, Geneva1981: 35-62
        • Japan Mammary Cancer Society
        Histologic classification of breast tumors.
        in: General rules for clinical and pathological record of mammary cancer. 14th ed. Kanehara, Tokyo2000: 19-56
        • Bloom H.J.G
        • Richardson W.W
        Histologic grading and prognosis in breast cancer: a study of 1049 cases of which 359 have been followed for 15 years.
        Br J Cancer. 1957; 11: 359-377
        • Kurusu Y
        • Yamashita J
        • Hayashi N
        • Mita S
        • Fujino N
        • Ogawa M
        The sequence of vessel ligation affects tumor release into the circulation.
        J Thorac Cardiovasc Surg. 1998; 116: 107-113
        • Chomczynski P
        • Sacchi N
        Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction.
        Anal Biochem. 1987; 162: 156-159
        • Kurusu Y
        • Yamashita J
        • Ogawa M
        Detection of circulating tumor cells by reverse transcriptase-polymerase chain reaction in patients with resectable non-small cell lung cancer.
        Surgery. 1999; 126: 820-826
        • Kaplan E.L
        • Meier P
        Nonparametric estimation for incomplete observations.
        J Am Stat Assoc. 1958; 53: 457-481
        • Mantel N
        • Haenszel W
        Statistical aspects of the analysis of data from retrospective studies of disease.
        J Natl Cancer Inst. 1959; 22: 719-748
        • Cox D.R
        Regression models and life-tables.
        J R Stat Soc [B]. 1972; 34: 187-220
        • Wyld D.K
        • Selby P
        • Perren T.J
        • Jonas S.K
        • Allen-Mersh T.G
        • Wheeldon J
        • et al.
        Detection of colorectal cancer cells in peripheral blood by reverse-transcriptase polymerase chain reaction for cytokeratin 20.
        Int J Cancer. 1998; 79: 288-293
        • Soeth E
        • Vogel I
        • Roder C
        • Juhl H
        • Marxsen J
        • Kruger U
        • et al.
        Comparative analysis of bone marrow and venous blood isolates from gastrointestinal cancer patients for the detection of disseminated tumor cells using reverse transcription PCR.
        Cancer Res. 1997; 57: 3106-3110
        • Yamashita J
        • Ogawa M
        • Kurusu Y
        • Matsuo A
        • Saishoji T
        • Fujino N
        • et al.
        Preoperative evidence of circulating tumor cells by reverse transcriptase-polymerase chain reaction for CEA mRNA is an independent predictor of survival in non-small cell lung cancer: A prospective study.
        J Thorac Cardiovasc Surg. 2002; 124: 299-305
        • Nishizaki T
        • Matsumata T
        • Kanematsu T
        • Yasunaga C
        • Sugimachi K
        Surgical manipulation of VX2 carcinoma in the rabbit liver evokes enhancement of metastases.
        J Surg Res. 1990; 49: 92-97
        • Yamashita J
        • Kurusu Y
        • Fujino N
        • Saishoji T
        • Ogawa M
        Detection of circulating tumor cells in patients with non-small cell lung cancer undergoing lobectomy by video-assisted thoracic surgery: a potential hazard for intraoperative hematogenous tumor cell dissemination.
        J Thorac Cardiovasc Surg. 2000; 119: 899-905
        • Glaves D
        • Huben R
        • Weiss L
        Haematogenous dissemination of cells from human renal adenocarcinoma.
        Br J Cancer. 1988; 54: 32-35
        • Janni W
        • Hepp F
        • Rjosk D
        • Kentenich C
        • Strobl B
        • Schindlbeck C
        • et al.
        The fate and prognostic value of occult metastatic cells in the bone marrow of patients with breast carcinoma between primary treatment and recurrence.
        Cancer. 2001; 92: 46-53