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Diagnostic Yield of Primary Circulating Tumor Cells in Women Suspected of Breast Cancer: the BEST (Breast Early Screening Test) Study

  • Murray, Nigel P (Hematology, Medicine, Faculty of Medicine, University Mayor, Hospital de Carabineros de Chile) ;
  • Miranda, Roxana (Breast Unit, Faculty of Medicine, University Mayor, Hospital de Carabineros de Chile) ;
  • Ruiz, Amparo (Pathology Service, Faculty of Medicine, University Mayor, Hospital de Carabineros de Chile) ;
  • Droguett, Elsa (Diagnostic Radiology, Faculty of Medicine, University Mayor, Hospital de Carabineros de Chile)
  • Published : 2015.03.18

Abstract

Purpose: To determine the diagnostic yield of primary circulating tumor cells in women with suspicion of breast cancer, detected as a result of an abnormal mammography. Materials and Methods: Consecutive women presenting for breast biopsy as a result of a mammogram BiRADs of 3 or more, had an 8ml blood sample taken for primary circulating tumor cell (CTC) detection. Mononuclear cells were obtained using differential gel centrifugation and CTCs identified using standard immunocytochemistry using anti-mammoglobin. A test was determined to be positive if 1 CTC was detected. Results: A total of 144 women with a mean age of $54.7{\pm}15.6$ years participated, 78/144 (53.0%) had breast cancer on biopsy, 65/140 (46.3%) benign pathologies and 1(0.7%) non-Hogkins lymphoma. Increasing BiRADs scores were associated with increased cancer detection (p=0.004, RR 1.00, 4.24, 8.50). CTC mammoglobin positive had a sensitivity of 81.1% and specificity of 90.9%, with positive and negative predictive values of 90.9% and 81.1% respectively. Mammoglobin positive CTCs detected 87% of invasive cancers, while poorly differentiated cancers were negative for mammoglobin. Only 50% of in situ cancers and none of the intraductal cancers had CTCs detected. Menopausal status did not affect the diagnostic yield of the CTC test, which was higher in women with BiRADS 4 mammograms. There was a significant trend (p<0.0001 Chi squared for trends) in CTC detection frequency from intraductal, in situ and invasive (OR 1.00, 8.00, 472.00). Conclusions: The use of primary CTC detection in women suspected of breast cancer has potential uses, especially with invasive cancer, but it failed to detect intra-ductal cancer and 50% of in situ cancer. There was no difference in the diagnostic yield between pre and post menopausal women. To confirm its use in reducing biopsies in women with BIRADs 4a mammagrams and in the detection of interval invasive breast cancer, larger studies are needed.

Keywords

Breast cancer detection;circulating tumor cells;mammogram;mammaglobin;BiRADS

References

  1. Ashworth TR (1869???). A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Med J Australia, 14, 146-9.
  2. Badve S, A'Hern RP, Ward AM, et al (1998). Prediction of local recurrence of ductal carcinoma in situ of the breast using five histological classifications, a comparative study with long follow-up. Hum Pathol, 29, 915-923. https://doi.org/10.1016/S0046-8177(98)90196-4
  3. Barton MB, Harris R, Fletcher SW (1999). The rational clinical examination. Does this patient have breast cancer? The screening clinical breast examination: should it be done? How? JAMA, 282, 1270-80. https://doi.org/10.1001/jama.282.13.1270
  4. Borgen E, Naume B, Nesland JM, et al (1999). Standardization of the immunocitochemical detection of cancer cells in bone marrow and blood, Establishment of objective criteria for the evaluation of immunostained cells. ISHAGE Cytotherapy, 5, 377-88.
  5. Buist DS, Porter PL, Lehman C, et al (2004). Factors contributing to mammography failure in women aged 40-49 years. J Natl Cancer Inst, 96, 1432-40. https://doi.org/10.1093/jnci/djh269
  6. Carey PA, Miglioretti DL, Yankaskas BC, et al (2003). Individual and combined effects of age, breast density and hormone replacement therapy use on the accuracy of mammographic screening. Ann Intern Med, 138, 168-175. https://doi.org/10.7326/0003-4819-138-3-200302040-00008
  7. Chen Y, Zou TN, Wu ZP, et al (2010), Detection of cytokeratin 19, human mammaglobin and CEA positive CTCs by three marker RT-PCR and its relation to clinical outcome in early breast cancer. Int J Biol Markers, 25, 59-68
  8. Collins LC, Tamimi RM, Baer HJ, et al (2005). Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy. Results from the Nurses' Health Study. Cancer, 103, 1778-84. https://doi.org/10.1002/cncr.20979
  9. Cristofanilli M, Budd T, Ellis MJ, et al (2004). Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med, 351, 781-91. https://doi.org/10.1056/NEJMoa040766
  10. Cristofanilli M (2006). Circulating tumor cells, disease progression, and survival in metastatic breast cancer. Semin Oncol, 33, 9-14.
  11. Ferro P, Franceschini MC, Bacigalupo B, et al (2010) Detection of CTCs in breast cancer patients using human mammaglobin RT-PCR, association with clinical prognostic factors. Anticancer Res, 30, 2377-82
  12. Franken B, de Groot MR, Mastboom WJ, et al (2012). Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer. Breast Cancer Res, 14, 133. https://doi.org/10.1186/bcr3333
  13. Gotzsche PC, Jorgensen KJ (2013). Screening for breast cancer with mammography. Cochrane Database Syst Rev, 6, 1877.
  14. Li G, Zhang J, Jin K, et al (2011) Human mammaglobin, a superior marker for RT-PCR in detecting CTCs in breast cancer patients. Biomark Med, 5, 249-60 https://doi.org/10.2217/bmm.11.20
  15. Lianidou ES, Markou A (2011). CTCs in breast cancer, detection systems, molecular characterization and future challenges. Clin Chem, 57, 1242. https://doi.org/10.1373/clinchem.2011.165068
  16. Lianidou ES, Markou A (2011a). CTCs as emerging biomarkers in breast cancer. Clin Chem Lab Med, 49, 1579-90
  17. Lynge E, Ponti A, James T et al, (2014) Variation in detection of ductal carcinoma in situ during screening mammography, a survey within the International Cancer Screening Network. Eur J Cancer, 50, 185-192
  18. NCCN guidelines breast cancer screening 2014. www.nccn.org
  19. Nemec CF, Listinsky J, Rim A. (2007) How should we screen for breast cancer? Mammography? Ultrasonography? MRI? Cleve Clin J Med, 74, 897-904 https://doi.org/10.3949/ccjm.74.12.897
  20. Ntoulia M, Stathopoulou A, Ignatiadis M, et al (2006). Detection of Mammaglobin A mRNA positive CTCs in peripheral blood of patients with operable breast cancer with nested RT-PCR. Clin Biochem, 39, 879-87 https://doi.org/10.1016/j.clinbiochem.2006.06.009
  21. Orel SG, Kay N, Reynolds C, et al (1999). BiRADS categorization as a predictor of malignancy. Radiology, 211, 845-50 https://doi.org/10.1148/radiology.211.3.r99jn31845
  22. Panteleakou Z, Lembessis P. Sourla A, et al (2009). Detection of circulating tumor cells in prostate cancer patients, methodological pitfalls and clinical relevance. Mol Med, 15, 101-14
  23. Paterlini-Brechot P, Benali NL (2007). Circulating tumor cells detection, clinical impact and future directions. Cancer Letters, 2, 180-204
  24. Raimondi C, Gradilone A. Naso G, et al (2011). Epithelialmesenchymal transition and stemness features in circulating tumor cells from breast cancer patients. Breast Cancer Res Treat. (Epub ahead of print).
  25. Riethdorf S, Wikman H, Pantel K (2008). Review, biological relevance of disseminated tumor cells in cancer patients. Int J Cancer, 123, 1991-2006. https://doi.org/10.1002/ijc.23825
  26. Tarhan MO, Gonel A, Kucukzeybek Y, et al (2013). Prognostic significance of circulating tumor cells and serum CA15-3 levels in metastatic breast cancer, single center experience, preliminary results. Asian Pac J Cancer Prev, 14, 1725-9. https://doi.org/10.7314/APJCP.2013.14.3.1725
  27. Turker I, Uyeturk U, Sonmez OU, et al (2013). Detection of circulating tumor cells in breast cancer patients: prognostic predictive role. Asian Pac J Cancer Prev, 14, 1601-7. https://doi.org/10.7314/APJCP.2013.14.3.1601
  28. Went PT, Lugli A, Meier S, et al (2004). Frequent EpCam protein expression in human carcinomas. Hum Pathol, 1, 122-8
  29. Xenidis N, Ignatiadis M, Apostolaki S, et al (2009). Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer, J Clin Oncol, 27, 2177-84. https://doi.org/10.1200/JCO.2008.18.0497

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