Abstract
Background. The recent introduction of sensitive RT-PCR-based techniques for the detection of epithelial antigen expression, such as CK-19, in the peripheral blood and bone marrow of breast cancer patients may provide an opportunity to evaluate tumor response at the molecular level, even in the absence of measurable disease while patients are still receiving chemotherapy.
Methods. We studied serially collected blood samples of 53 patients with breast cancer before, during, and after adjuvant, neoadjuvant, and palliative chemotherapy to evaluate its effects on the expression of CK-19 measured by RT-PCR.
Results. The percentage of CK-19 RT-PCR positivity decreased consistently from 43% (23/53) before chemotherapy to 14.3% (7/49), and to 18.9% (7/37) after 3 and 6 cycles, respectively (chi-square for linear trend=7.948; p=0.0048). Furthermore, there was a significant correlation between a negative CK-19 at three months and the response to chemotherapy (p=0.024).
Conclusion. We conclude that RT-PCR negativity for CK-19 expression at 3 months after the beginning of chemotherapy correlates with tumor response and, as treatment progresses, there is a significant trend for the occurrence of more negative RT-PCR results. Further studies are needed to confirm if this technique can be useful to assess response to chemotherapy in patients without measurable disease and if negativation of CK-19 expression while on chemotherapy is of prognostic significance.
References
Early Breast Cancer Trialists' Group: Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet 352: 930-942, 1998
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92: 205-216, 2000
Datta YH, Adams PT, Drobyski WR, Ethier SP, Terry VH, Roth MS: Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction. J Clin Oncol 12: 475-482, 1994
Smith BM, Slade MJ, English J, Graham H, Lüchtenborg M, Sinnett HD, Cross NNNCP, Coombes RC: Response of circulating tumor cells to systemic therapy in patients with metastatic breast cancer: comparision of quantitative polymerase chain reaction and immunocytochemical techniques. J Clin Oncol 18: 1432-1439, 2000
Bordow SB, Haber M, Madafiglio J, Cheung B, Marshall GM, Norris MD: Expression of the multidrug resistance-associated protein (MRP) gene correlates with amplification and overexpression of the N-myc oncogene in childhood neuroblastoma. Cancer Res 54: 5036-5040, 1994
Ruud P, Fodstad O, Hovig E: Identification of a novel cytokerat in 19 pseudogene that may interfere with reverse transcriptase-polymerase chain reaction assays used to detect micrometastatic tumor cells. Int J Cancer 80: 119-125, 1999
Braun S, Pantel K, Muller P, Janni W, Hepp F, Kentenich CR, Gastroph S, Wischnik A, Dimpfl T, Kindermann G, Riethmuller G, Schlimok G: Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med 342: 525-533, 2000
Diel IJ, Kaufmann M, Costa SD, Holle R, von Minckwitz G, Solomayer EF, Kaul S, Bastert G: Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst 88: 1652-1658, 1996
Gluck S, Ross AA, Layton TJ, Ostrander AB, Goldstein LC, Porter K, Ho AD: Decrease in tumor cell contamination and progenitor cell yield in leukapheresis products after consecutive cycles of chemotherapy for breast cancer treatment. Biol Blood Marrow Transplant 3: 316-323, 1997
Schulze R, Schulze M, Wischnik A, Ehnle S, Doukas K, Behr W, Ehret W, Schlimok G: Tumor cell contamination of peripheral blood stem cell transplants and bone marrow in high-risk breast cancer patients. Bone Marrow Transplant 19: 1223-1228, 1997
Braun S, Kentenich C, Janni W, Hepp F, deWaal J, Willgeroth F, Sommer H, Pantel K: Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in bone marrow of high-risk breast cancer patients. J Clin Oncol 18: 80-86, 2000
Battaglia M, Pedrazzoli P, Palermo B, Lanza A, Bertolini F, Gibelli N, Da Prada GA, Zambelli A, Perotti C, Robustelli della Cuna G: Epithelial tumour cell detection and the unsolved problems of nested RT-PCR: a new sensitive one step method without false positive results. Bone Marrow Transplant 22: 693-698, 1998
Krismann M, Todt B, Schroder J, Gareis D, Muller KM, Seeber S, Schutte J: Low specificity of cytokeratin 19 reverse transcriptase-polymerase chain reaction analyses for detection of hematogenous lung cancer dissemination. J Clin Oncol 13: 2769-2775, 1995
Novaes M, Bendit I, Garicochea B, del Giglio A: Reverse transcriptase-polymerase chain reaction analysis of cytokeratin 19 expression in the peripheral blood mononuclear cells of normal female blood donors. Mol Pathol 50: 209-211, 1997
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Manhani, A.R., Manhani, R., Soares, H.P. et al. CK-19 Expression by RT-PCR in the Peripheral Blood of Breast Cancer Patients Correlates with Response to Chemotherapy. Breast Cancer Res Treat 66, 249–254 (2001). https://doi.org/10.1023/A:1010621901102
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DOI: https://doi.org/10.1023/A:1010621901102