The American Journal of Surgery
Volume 186, Issue 4 , Pages 351-358 , October 2003

The molecular detection of micrometastatic breast cancer

Presented at the Fourth Annual Meeting of the American Society of Breast Surgeons, Atlanta, Georgia, April 30–May 4, 2003.

  • Megan Baker, M.D.

      Affiliations

    • Medical University of South Carolina, Department of Surgery, 171 Ashley Ave., Room 420Q CSB, Charleston, SC 29425, USA
    • ,
  • William E Gillanders, M.D.

      Affiliations

    • Medical University of South Carolina, Department of Surgery, 171 Ashley Ave., Room 420Q CSB, Charleston, SC 29425, USA
    • ,
  • Kaidi Mikhitarian, M.D.

      Affiliations

    • Medical University of South Carolina, Department of Surgery, 171 Ashley Ave., Room 420Q CSB, Charleston, SC 29425, USA
    • ,
  • Michael Mitas, Ph.D.

      Affiliations

    • Medical University of South Carolina, Department of Surgery, 171 Ashley Ave., Room 420Q CSB, Charleston, SC 29425, USA
    • ,
  • David J Cole, M.D.

      Affiliations

    • Medical University of South Carolina, Department of Surgery, 171 Ashley Ave., Room 420Q CSB, Charleston, SC 29425, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1-843-792-4638; fax: +1-843-792-3315.

Received 3 June 2003 ,Revised 21 June 2003

References 

  1. Ries LAG, Henson DE, Harras A. Survival from breast cancer according to tumor size and nodal status. Surg Oncol Clin North Am. 1994;3:391–395
  2. Valgussa P, Bonadonna G, Veronesi U, et al. Patterns of relapse and survival following radical mastectomy. Cancer 1978;41:1170–8
  3. Cady B. The need to reexamine axillary lymph node dissection in invasive breast cancer. Cancer. 1994;73:505–508
  4. Chadha M, Axelrod D. Is axillary dissection always indicated in invasive breast cancer?. Oncology. 1997;11:1463–1468
  5. Chontos AJ, Maher DP, Ratzer ER, Fenoglio ME. Axillary lymph node dissection (is it required in T1a breast cancer?). J Am Coll Surg. 1997;184:493–498
  6. Fisher B, Redmond C, Fisher ER, et al.  Ten-year results of a randomized trial comparing radical mastectomy and total mastectomy with or without radiation. N Engl J Med. 1985;312:674–681
  7. Fisher B, Wolmark N, Bauer M, et al.  The accuracy of clinical nodal staging and of limited axillary dissection as a determinant of histologic nodal status in carcinoma of the breast. Surg Gynecol Obstet. 1981;152:765–772
  8. Schwarzinger I, Valent P, Koller U, et al.  Prognostic significance of surface marker expression on blasts of patients with de nova acute myeloblastic leukemia. J Clin Oncol. 1990;8:423–430
  9. Gardner B FJ. Are positive axillary nodes in breast cancer markers for incurable disease? Ann Surg 1993;218–270–7
  10. Berns EM, Klijn JG, van Putten WL, et al.  C-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer. Cancer Res. 1992;52:1107–1113
  11. Datta YH, Adams PT, Drobyski WR, et al.  Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction. J Clin Oncol. 1994;12:475–482
  12. Gasparini G, Toi M, Gion M, et al.  Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst. 1997;89:139–147
  13. Ioachim E, Kamina S, Athanassiadou S, Agnantis NJ. The prognostic significance of epidermal growth factor receptor (EGFR), C-erbB-2, Ki-67 and PCNA expression in breast cancer. Anticancer Res. 1996;16:3141–3147
  14. Anan K, Morisaki T, Katano M, et al.  Assessment of c-erbB2 and vascular endothelial growth factor mRNA expression in fine-needle aspirates from early breast carcinomas (pre-operative determination of malignant potential). Eur J Surg Oncol. 1998;24:28–33
  15. Bieche I, Lazar V, Nogues C, et al.  Prognostic value of chorionic gonadotropin beta gene transcripts in human breast carcinoma. Clin Cancer Res. 1998;4:671–676
  16. Harbeck N, Dettmar P, Thomssen C, et al.  Prognostic impact of tumor biological factors on survival in node-negative breast cancer. Anticancer Res. 1998;18:2187–2197
  17. Linderholm B, Tavelin B, Grankvist K, Henriksson R. Vascular endothelial growth factor is of high prognostic value in node-negative breast carcinoma. J Clin Oncol. 1998;16:3121–3128
  18. Lockett MA, Baron PL, O'Brien PH, et al.  Detection of occult breast cancer micrometastases in axillary lymph nodes using a multimarker reverse transcriptase-polymerase chain reaction panel. J Am Coll Surg. 1998;187:9–16
  19. Molina R, Jo J, Filella X, et al.  C-erbB-2 oncoprotein, CEA, and CA 15.3 in patients with breast cancer (prognostic value). Breast Cancer Res Treat. 1998;51:109–119
  20. Pathak KA, Khanna R, Khanna HD, et al.  Carcinoembryonic antigen (an invaluable marker for advanced breast cancer). J Postgrad Med. 1996;42:68–71
  21. Raj GV, Moreno JG, Gomella LG, et al. Utilization of polymerase chain reaction technology in the detection of solid tumors. Cancer 1998;82:1419–1442
  22. Houghton R, Dillon D, Molesh D, et al.  Transcriptional complementarity in breast cancer (application to detection of circulating tumor cells). Molec Diagn. 2001;6:79–91
  23. McGuckin MA, Cummings MC, Walsh MD, et al.  Occult axillary node metastases in breast cancer (their detection and prognostic significance). Br J Cancer. 1996;73:88–95
  24. Neville AM, Bettelheim R, Gelber RD, Goldhirsch A. Occult axillary lymph-node micrometastases in breast cancer. Lancet. 1990;336:759
  25. Neville AM, Price KN, Gelber RD, Goldhirsch A. Axillary node micrometastases and breast cancer. Lancet. 1991;337:1110
  26. Diel IJ, Kaufmann M, Goerner R, et al.  Detection of tumor cells in bone marrow of patients with primary breast cancer (a prognostic factor for distant metastasis). J Clin Oncol. 1992;10:1534–1539
  27. Turner R, Giuliano A, Hoon DS, et al.  Pathologic examination of sentinel lymph node for breast carcinoma. World J Surg. 2001;25:798–805
  28. Turner R, Ollila D, Stern S, Giuliano A. Optimal histopahtologic examination of the sentinel lymph node for breast carcinoma staging. Am J Surg Pathol. 1999;23:263
  29. Lockett MA, Metcalf JS, Baron PL, et al.  Efficacy of reverse transcriptase-polymerase chain reaction screening for micrometastic disease in axillary lymph nodes of breast cancer patients. Am Surg. 1998;64:539–544
  30. Turner RR, Ollila DW, Krasne DL, Giuliano AE. Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma. Ann Surg. 1997;226:271
  31. Wong S, Chao C, Edwards M, et al.  The use of cytokeratin staining in sentinel lymph node biopsy for breast cancer. Am J Surg. 2001;182:330–334
  32. Ghossein RA, Carusone L, Bhattacharya S. Polymerase chain reaction detection of micrometastases and circulating tumor cells (application to melanoma, prostate, and thyroid carcinomas). Diagn Mol Pathol. 1999;8:165–175
  33. Ghossein R, Bhattacharya S. Molecular detection and characterization of circulating tumor cells and micrometastases in solid tumors. Eur J Cancer. 2000;36:1681–1694
  34. Noguchi S, Aihara T, Motomura K, et al.  Detection of breast cancer micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction. Comparison between MUC1 mRNA and keratin 19 mRNA amplification. Am J Pathol. 1996;148:649–656
  35. Mitas M, Mikhitarian K, Walters C, et al.  Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel. Int J Cancer. 2001;93:162–171
  36. Shivers SC, Stall A, Goscin C, et al.  Molecular staging for melanoma and breast cancer. Surg Oncol Clin North Am. 1999;8:515–526
  37. Fields KK, Elfenbein GJ, Trudeau WL, et al. Clinical significance of bone marrow metastases detected using polymerase chain reaction inpatients with breast cancer undergoing high dose chemotherapy and autologous bone marrow transplantation. J Clin Oncol 1998;6:1868–76
  38. Smith BM, Slade MJ, English J, et al. Response of circulating tumor cells to systemic therapy in patients with metastastic breast cancer: comparison of quantitative polymerase chain reaction and immunocytochemical techniques. J Clin Oncol 2000;18:1432–9
  39. Berois N, Varangot M, Aizen B, et al.  Molecular detection of cancer cells in bone marrow and peripheral blood of patients with operable breast cancer. Comparison of CK19, MUC1, and CEA using RT-PCR. Eur J Cancer. 2000;36:717–723
  40. Bostick PJ, Chatterjee S, Chi DD, et al.  Limitations of specific reverse-transcriptase polymerase chain reaction markers in the detection of metastases in the lymph nodes and blood of breast cancer patients. J Clin Oncol. 1998;16:2632–2640
  41. Eltahir EM, Mallinson DS, Birnie GD, et al.  Putative markers for the detection of breast carcinoma cells in blood. Br J Cancer. 1998;77:1203–1207
  42. Goeminne JC, Guillaume T, Salmon M, et al.  Unreliability of carcinoembryonic antigen (CEA) reverse transcriptase-polymerase chain reaction (RT-PCR) in detecting contaminating breast cancer cells in peripheral blood stem cells due to induction of CEA by growth factors. Bone Marrow Transplant. 1999;24:769–775
  43. Gunn J, McCall JL, Yun K, Wright PA. Detection of micrometastases in colorectal cancer patients by K19 and K20 reverse-transcription polymerase chain reaction. Lab Invest. 1996;75:611–616
  44. Lopez-Guerrero JA, Gilabert PB, Gonzalez EB, et al.  Use of reverse-transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen, cytokeratin 19, and maspin in the detection of tumor cells in leukapheresis products from patients with breast cancer (comparison with immunocytochemistry). J Hematother. 1999;8:53–61
  45. Merrie AE, Yun K, Gunn J, et al.  Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer. Br J Cancer. 1999;80:2019–2024
  46. Zach O, Kasparu H, Krieger O, et al.  Detection of circulating mammary carcinoma cells in the peripheral blood of breast cancer patients via a nested reverse transcriptase polymerase chain reaction assay for mammoglobin mRNA. J Clin Oncol. 1999;17:2015–2019
  47. Zhong XY, Kaul S, Diel I, et al.  Analysis of sensitivity and specificity of cytokeratin 19 reverse transcriptase/polymerase chain reaction for detection of occult breast cancer in bone marrow and leukapheresis products. J Cancer Res Clin Oncol. 1999;125:286–291
  48. Manzotti M, Dell'Orto P, Maisonneuve P, et al.  Reverse transcription-polymerase chain reaction assay for multiple mRNA markers in the detection of breast cancer metastases in sentinel lymph nodes. Int J Cancer. 2001;95:307–312
  49. Heid CA, Stevens J, Livak KJ, Williams PM. Real time quantitative PCR. Genome Res. 1996;6:986–994
  50. Bieche I, Laurendeau I, Tozlu S, et al.  Quantitation of MYC gene expression in sporadic breast tumors with a real-time reverse transcription-PCR assay. Cancer Res. 1999;59:2759–2765
  51. West M, Blanchette C, Dressman H, et al.  Predicting the clinical status of human breast cancer by using gene expression profiles. Proc Natl Acad Sci. 2001;98:11462–11467
  52. Sorle T, Perou C, Tibshirani R, et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci. 2001;98:10869–10874
  53. van't Veer LJ, Dai H, van de Vijver MJ, et al.  Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530–536
  54. Smith BM, Slade MJ, English J, et al.  Response of circulating tumor cells to systemic therapy in patients with metastatic breast cancer (comparison of quantitative polymerase chain reaction and immunocytochemical techniques). J Clin Oncol. 2000;18:1432–1439
  55. Slade MJ, Smith BM, Sinnett HD, et al.  Quantitative polymerase chain reaction for the detection of micrometastases in patients with breast cancer. [published erratum appears in J Clin Oncol 1999;17:1330] J Clin Oncol. 1999;17:870–879
  56. Cabanes PA, Salmon RJ, Vilcoq JR, et al.  Value of axillary dissection in addition to lumpectomy and radiotherapy in early breast cancer. Lancet. 1992;339:1245–1248
  57. Schoenfeld A, Luqmani Y, Smith D, et al.  Detection of breast cancer micrometastases in axillary lymph nodes by using polymerase chain reaction. Cancer Res. 1994;54:2986–2990
  58. Janni W, Hepp F, Rjosk D, 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
  59. Gebauer G, Fehm T, Merkle E, et al.  Epithelial cells in bone marrow of breast cancer patients at time of primary surgery (clinical outcome during long-term follow-up). J Clin Oncol. 2001;19:3669–3674
  60. Funke I, Schraut W. Meta-analysis of studies on bone marrow micrometastases (an independent prognostic impact remains to be substantiated). J Clin Oncol. 1998;16:557–566
  61. Pantel K, Cote RJ, Fodstad O. Detection and clinical importance of micrometastic disease. J Natl Cancer Inst. 1999;91:1113–1124
  62. Braun S, Harbeck N. Recent advances in technologies for the detection of occult metastatic cells in bone marrow of breast cancer patients. Breast Cancer Res. 2001;3:285–288
  63. Braun S, Pantel K, Muller P, et al.  Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. [see comments] N Engl J Med. 2000;342:525–533
  64. Aerts J, Wynendaele W, Paridaens R, et al.  A real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to detect breast carcinoma in peripheral blood. Ann Oncol. 2001;12:39–46
  65. Slade M. Quantitative polymerase chain reaction for the detection of micrometastases in patients with breast cancer. J Clin Oncol. 1999;17:870–879
  66. Noguchi S, Aihara T, Nakamori S, et al.  The detection of breast carcinoma micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction. Cancer. 1994;74:1595–1600
  67. de Cremoux P, Extra JM, Denis MG, et al.  Detection of MUC1-expressing mammary carcinoma cells in the peripheral blood of breast cancer patients by real-time polymerase chain reaction. [in process citation] Clin Cancer Res. 2000;6:3117–3122
  68. Taback B, Chan AD, Kuo CT, et al.  Detection of occult metastatic breast cancer cells in blood by a multimolecular marker assay (correlation with clinical stage of disease). Cancer Res. 2001;61:8845–8850
  69. Soria JC, Gauthier LR, Raymond E, et al.  Molecular detection of telomerase-positive circulating epithelial cells in metastatic breast cancer patients. Clin Cancer Res. 1999;5:971–975
  70. Watson MA, Dintzis S, Darrow CM, et al.  Mammaglobin expression in primary, metastatic, and occult breast cancer. Cancer Res. 1999;59:3028–3031
  71. Hedenfalk I, Duggan D, Chen Y, et al.  Gene-expression profiles in hereditary breast cancer. N Engl J Med. 2001;344:539–548
  72. Grunewald K, Haun M, Urbanek M, et al.  Mammaglobin gene expression (a superior marker of breast cancer cells in peripheral blood in comparison to epidermal-growth-factor receptor and cytokeratin-19). Lab Invest. 2000;80:1071–1077
  73. Beitsch PD, Clifford E. Detection of carcinoma cells in the blood of breast cancer patients. Am J Surg. 2001;180:446–449
  74. Evron E, Dooley W, Umbricht C, et al.  Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR. Lancet. 2001;357:1335–1336
  75. Dooley W, Ljung B, Veronesi U, et al.  Ductal lavage for detection of cellular atypia in women at high risk for breast cancer. J Natl Cancer Inst. 2001;93:1624–1632

PII: S0002-9610(03)00262-9

doi: 10.1016/S0002-9610(03)00262-9

The American Journal of Surgery
Volume 186, Issue 4 , Pages 351-358 , October 2003

Article Tools

* Image Usage & Resolution