Skip to main content

Breast Cancer Screening and Biomarkers

  • Protocol
Cancer Epidemiology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 472))

Abstract

Annual screening mammograms have been shown to be cost-effective and are credited for the decline in mortality of breast cancer. New technologies including breast magnetic resonance imaging (MRI) may further improve early breast cancer detection in asymptomatic women. Serum tumor markers such as CA 15-3, carcinoembyonic antigen (CEA), and CA 27–29 are ordered in the clinic mainly for disease surveillance, and not useful for detection of localized cancer. This review will discuss blood-based markers and breast-based markers, such as nipple/ductal fluid, with an emphasis on biomarkers for early detection of breast cancer. In the future, it is likely that a combination approach to simultaneously measure multiple markers would be most successful in detecting early breast cancer. Ideally, such a biomarker panel should be able to detect breast cancer in asymptomatic patients, even in the setting of normal mammogram and physical examination results.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., and Thun, M.J. (2007) Cancer statistics, 2007. CA Cancer J. Clin. 57 , 43 – 66.

    PubMed  Google Scholar 

  2. Rimer, B.K., Schildkraut, J.M., and Hiatt, R.A. (2005) Cancer screening. In: DeVita, V.T., Hellman, S., and Rosenberg, S.A., eds. Cancer: principles and practice of oncology. Philadelphia, PA: Lippincott—Raven, 567 – 579.

    Google Scholar 

  3. American Cancer Society. (2007) Cancer facts & figures 2007. Atlanta: American Cancer Society.

    Google Scholar 

  4. Shapiro, S. (1997) Periodic screening for breast cancer: the HIP Randomized Controlled Trial. Health Insurance Plan. J. Natl. Cancer Inst. Monogr. 22 , 27 – 30.

    PubMed  Google Scholar 

  5. Hendrick, R.E., Smith, R.A., Rutledge, J.H., and Smart, C.R. (1997) Benefit of screening mammography in women aged 40 – 49: a new meta–analysis of randomized controlled trials. J. Natl. Cancer Inst. Monogr. 22, 87–92.

    PubMed  Google Scholar 

  6. Andersson, I., Aspegren, K., Janzon, L., Landberg, T., Lindholm, K., Linell, F., Ljungberg, O., Ranstam, J., and Sigfússon, B. (1998) Mammographic screening and mortality from breast cancer: the Malm ö mammographic screening trial. BMJ 297, 943–948.

    Google Scholar 

  7. Tabér, L., Vitak, B., Chen, H.H., Duffy, S.W., Yen, M.F., Chiang, C.F., Krusemo, U.B., Tot, T., and Smith, R.A. (2000) The Swedish Two-County Trial twenty years later. Updated mortality results and new insights from long—term follow-up. Radiol. Clin. North Am. 38, 625–651.

    Google Scholar 

  8. Humphrey, L.L., Helfand, M., Chan, B.K., and Woolf, S.H. (2002) Breast cancer screening: a summary of the evidence for the U.S. Preventive Services Task Force. Ann. Intern. Med. 137, 347–360.

    PubMed  Google Scholar 

  9. Alexander, F.E., Anderson, T.J., Brown, H.K., Forrest, A.P., Hepburn, W., Kirk-patrick, A.E., Muir, B.B., Prescott, R.J., and Smith, A. (1999) 14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening. Lancet 353, 1903–1908.

    CAS  PubMed  Google Scholar 

  10. Miller, A.B., To, T., Baines, C.J., and Wall, C. (2000) Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50–59 years. J. Natl. Cancer Inst. 92, 1490–1499.

    CAS  PubMed  Google Scholar 

  11. Miller, A.B., To, T., Baines, C.J., and Wall, C. (2002) The Canadian National Breast Screening Study-1: breast cancer mortality after 11 to 16 years of follow-up. A randomized screening trial of mammography in women age 40 to 49 years. Ann. Intern. Med. 137, 305–312.

    PubMed  Google Scholar 

  12. Smart, C.R., Hendrick, R.E., Rutledge, J.H., and Smith, R.A. (1995) Benefit of mammography screening in women ages 40 to 49 years. Current evidence from randomized controlled trials. Cancer 75, 1619–1626.

    CAS  PubMed  Google Scholar 

  13. Esserman, L., Cowley, H., Eberle, C., Kirk-patrick, A., Chang, S., Berbaum, K., and Gale, A. (2002) Improving the accuracy of mammography: volume and outcome relationships. J. Natl. Cancer Inst. 94 , 369–375.

    PubMed  Google Scholar 

  14. Pisano, E.D., Gatsonis, C., Hendrick, E., Yaffe, M., Baum, J.K., Acharyya, S., Conant, E.F., Fajardo, L.L., Bassett, L., D'Orsi, C., Jong, R., Rebner, M., and Digital Mammographic Imaging Screening Trial (DMIST) Investigators Group. (2005) Diagnostic performance of digital versus film mammography for breast-cancer screening. N. Engl. J. Med. 353, 1773–1783.

    CAS  PubMed  Google Scholar 

  15. Fenton, J.J., Taplin, S.H., Carney, P.A., Abraham, L., Sickles, E.A., D'Orsi, C., Berns, E.A., Cutter, G., Hendrick, R.E., Barlow, W.E., and Elmore, J.G. (2007) Influence of computer-aided detection on performance of screening mammography. N. Engl. J. Med. 356, 1399–1409.

    CAS  PubMed  Google Scholar 

  16. Hall, F.M. (2007) Breast imaging and computer-aided detection. Engl. J. Med. 356, 1464–1466.

    CAS  Google Scholar 

  17. Berg, W.A. (2003) Rationale for a trial of screening breast ultrasound: American College of Radiology Imaging Network (ACRIN) 6666. Am. J. Roentgenol. 180, 1225–1228.

    Google Scholar 

  18. Berg, W.A., Blume, J.D., Cormack, J.B., Mendelson, E.B., Madsen, E.L., and ACRIN 6666 Investigators. (2006) Lesion detection and characterization in a breast US phantom: results of the ACRIN 6666 Investigators. Radiology 239 , 693–702.

    PubMed  Google Scholar 

  19. Morris, E.A., Liberman, L., Ballon, D.J., Robson, M., Abramson, A.F., Heerdt, A., and Dershaw, D.D. (2003) MRI of occult breast carcinoma in a high-risk population. Am. J. Roentgenol. 181, 619–626.

    Google Scholar 

  20. Lehman, C.D., Gatsonis, C., Kuhl, C.K., Hendrick, R.E., Pisano, E.D., Hanna, L., Peacock, S., Smazal, S.F., Maki, D.D., Julian, T.B., DePeri, E.R., Bluemke, D.A., Schnall, M.D., and ACRIN Trial 6667 Investigators Group. (2007) MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N. Engl. J. Med. 356, 1295–1303.

    CAS  PubMed  Google Scholar 

  21. Breen, N., Cronin, K., Meissner, H.I., Taplin, S.H., Tangka, F.K., Tiro, J.A., and McNeel, T.S. (2007) Reported drop in mammography: is this cause for concern? Cancer 109, 2405–2409.

    PubMed  Google Scholar 

  22. Ravdin, P.M., Cronin, K.A., Howlader, N., Berg, C.D., Chlebowski, R.T., Feuer, E.J., Edwards, B.K., and Berry, D.A. (2007) The decrease in breast–cancer incidence in 2003 in the United States. N. Engl. J. Med. 356, 1670–1674.

    CAS  PubMed  Google Scholar 

  23. Stearns, V., Yamauchi, H., and Hayes, D.F. (1998) Circulating tumor markers in breast cancer: accepted utilities and novel prospects. Breast Cancer Res. Treat. 52, 239–259.

    CAS  PubMed  Google Scholar 

  24. Duffy, M.J. (2006) Serum tumor markers in breast cancer: are they of clinical value? Clin. Chem. 52, 345–351.

    CAS  PubMed  Google Scholar 

  25. Bast, R.C., Ravdin, P., Hayes, D.F., Bates, S., Fritsche, H., Jessup, J.M., Kemeny, N., Locker, G.Y., Mennel, R.G., Somerfield, M.R., and American Society of Clinical Oncology Tumor Markers Expert Panel. (2001) 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J. Clin. Oncol. 19, 1865–1878.

    PubMed  Google Scholar 

  26. Molina, R., Barak, V., van Dalen, A., Duffy, M.J., Einarsson, R., Gion, M., Goike, H., Lamerz, R., Nap, M., S ö l é tormos, G., and Stieber, P. (2005) Tumor markers in breast cancer — European Group on Tumor Markers recommendations. Tumour Biol. 26 , 281–293.

    PubMed  Google Scholar 

  27. Pepe, M.S., Etzioni, R., Feng, Z., Potter, J.D., Thompson, M.L., Thornquist, M., Winget, M., and Yasui, Y. (2001) Phases of biomarker development for early detection of cancer. J. Natl. Cancer Inst. 93, 1054–1061.

    CAS  PubMed  Google Scholar 

  28. Ntoulia, M., Stathopoulou, A., Ignati-adis, M., Malamos, N., Mavroudis, D., Georgoulias, V., and Lianidou, E.S. (2006) Detection of Mammaglobin A-mRNA-positive circulating tumor cells in peripheral blood of patients with operable breast cancer with nested RT-PCR. Clin. Biochem. 39, 879–887.

    CAS  PubMed  Google Scholar 

  29. Cristofanilli, M., Budd, G.T., Ellis, M.J., Stopeck, A., Matera, J., Miller, M.C., Reuben, J.M., Doyle, G.V., Allard, W.J., Terstappen, L.W., and Hayes, D.F. (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med. 351, 781–791.

    CAS  PubMed  Google Scholar 

  30. Müller, V., Hayes, D.F., and Pantel, K. (2006) Recent translational research: circulating tumor cells in breast cancer patients. Breast Cancer Res. 8, 110.

    PubMed  Google Scholar 

  31. Lacroix, M. (2006) Significance, detection and markers of disseminated breast cancer cells. Endocr. Relat. Cancer 13, 1033–1067.

    CAS  PubMed  Google Scholar 

  32. F ü rstenberger, G., von Moos, R., Lucas, R., Th ü rlimann, B., Senn, H.J., Hamacher, J., and Boneberg, E.M. (2006) Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer. Br. J. Cancer 94, 524–531.

    Google Scholar 

  33. Fournié , G.J., Gayral-Taminh, M., Bouché, J.P., and Conté , J.J. (1986) Recovery of nanogram quantities of DNA from plasma and quantitative measurement using labeling by nick translation. Anal. Biochem. 158, 250–256.

    PubMed  Google Scholar 

  34. Zhong, X.Y., Bürk, M.R., Troeger, C., Kang, A., Holzgreve, W., and Hahn, S. (2000) Fluctuation of maternal and fetal free extracellular circulatory DNA in maternal plasma. Obstet. Gynecol. 96, 991–996.

    CAS  PubMed  Google Scholar 

  35. Zanetti–Dallenbach, R.A., Schmid, S., Wight, E., Holzgreve, W., Ladewing, A., Hahn, S., and Zhong, X.Y. (2007) Levels of circulating cell-free serum DNA in benign and malignant breast lesions. Int. J. Biol. Markers 22 , 95–99.

    PubMed  Google Scholar 

  36. Levenson, V.V. (2007) Biomarkers for early detection of breast cancer: what, when, and where? Biochim. Biophys. Acta. 1770, 847–856.

    CAS  PubMed  Google Scholar 

  37. Umetani, N., Giuliano, A.E., Hiramatsu, S.H., Amersi, F., Nakagawa, T., Martino, S., and Hoon, D.S. (2006) Prediction of breast tumor progression by integrity of free circulating DNA in serum. J. Clin. Oncol. 24, 4270–4276.

    CAS  PubMed  Google Scholar 

  38. Silva, J.M., Silva, J., Sanchez, A., Garcia, J.M., Dominguez, G., Provencio, M., Sanfrutos, L., Jareño, E., Colas, A., Espa ña, P., and Bonilla, F. (2002) Tumor DNA in plasma at diagnosis of breast cancer patients is a valuable predictor of disease—freesurvival. Clin. Cancer Res. 8, 3761–3766.

    CAS  PubMed  Google Scholar 

  39. Rykova, E.Y., Wunsche, W., Brizgunova, O.E., Skvortsova, T.E., Tamkovich, S.N., Senin, I.S., Laktionov, P.P., Sczakiel, G., and Vlassov, V.V. (2006) Concentrations of circulating RNA from healthy donors and cancer patients estimated by different methods. Ann. N.Y. Acad. Sci. 1075, 328–333.

    CAS  PubMed  Google Scholar 

  40. Schwarzenbach, H., Müller, V., Stahmann, N., and Pantel, K. (2004) Detection and characterization of circulating microsatellite—DNA in blood of patients with breast cancer. Ann. N.Y. Acad. Sci. 1022, 25–32.

    CAS  PubMed  Google Scholar 

  41. Herman, J.G. and Baylin, S.B. (2003) Gene silencing in cancer in association with promoter hypermethylation. N. Engl. J. Med. 349, 2042–2054.

    CAS  PubMed  Google Scholar 

  42. Kagan, J., Srivastava, S., Barker, P.E., Belinsky, S.A., and Cairns, P. (2007) Towards clinical application of methylated DNA sequences as cancer biomarkers: a joint NCI's EDRN and NIST workshop on standards, methods, assays, reagents and tools. Cancer Res. 67, 4545–4549.

    CAS  PubMed  Google Scholar 

  43. Evron, E., Dooley, W.C., Umbricht, C.B., Rosenthal, D., Sacchi, N., Gabrielson, E., Soito, A.B., Hung, D.T., Ljung, B.M., Davidson, N.E., and Sukumar, S. (2001) Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR. Lancet 357, 1335–1336.

    CAS  PubMed  Google Scholar 

  44. Honorio, S., Agathanggelou, A., Schuer-mann, M., Pankow, W., Viacava, P., Maher, E.R., and Latif, F. (2003) Detection of RASSF1A aberrant promoter hypermethylation in sputum from chronic smokers and ductal carcinoma in situ from breast cancer patients. Oncogene 22, 147–150.

    CAS  PubMed  Google Scholar 

  45. Jeronimo, C., Monteiro, P., Henrique, R., Dinis-Ribeiro, M., Costa, I., Costa, V.L., Filipe, L., Carvalho, A.L., Hoque, M.O., Pais, I., Leal, C., Teixeira, M.R., and Sidransky, D. (2008) Quantitative hypermethylation of a small panel of genes augments the diagnostic accuracy in fine-needle aspirate washings of breast lesions. Breast Cancer Res. Treat. 109, 27–34.

    CAS  PubMed  Google Scholar 

  46. Silva, J.M., Dominguez, G., Villanueva, M.J., Gonzalez, R., Garcia, J.M., Corbacho, C., Provencio, M., España, P. , and Bonilla, F. (1999) Aberrant DNA methylation of the p16INK4a gene in plasma DNA of breast cancer patients. Br. J. Cancer 80, 1262–1264.

    CAS  PubMed  Google Scholar 

  47. Krassenstein, R., Sauter, E., Dulaimi, E., Battagli, C., Ehya, H., Klein-Szanto, A., and Cairns, P. (2004) Detection of breast cancer in nipple aspirate fluid by CpG island hyper-methylation. Clin. Cancer Res. 10, 28–32.

    CAS  PubMed  Google Scholar 

  48. Dulaimi, E., Hillinck, J., Ibanez de Caceres, I., Al-Saleem, T., and Cairns, P. (2004) Tumor suppressor gene promoter hypermethylation in serum of breast cancer patients. Clin. Cancer Res. 10, 6189–6193.

    CAS  PubMed  Google Scholar 

  49. Hoque, M.O., Feng, Q., Toure, P., Dem, A., Critchlow, C.W., Hawes, S.E., Wood, T., Jeronimo, C., Rosenbaum, E., Stern, J., Yu, M., Trink, B., Kiviat, N.B., and Sidransky, D. (2006) Detection of aberrant methylation of four genes in plasma DNA for the detection of breast cancer. J. Clin. Onc. 24, 4262–4269.

    CAS  Google Scholar 

  50. Jing, F., Zhang, J., Tao, J., Zhou, Y., Jun, L., Tang, X., Wang, Y., and Hai, H. (2007) Hypermethylation of tumor suppressor genes BRCA1, p16 and 14-3-3sigma in serum of sporadic breast cancer patients. Onkologie 30, 14–19.

    CAS  PubMed  Google Scholar 

  51. Sharma, G., Mirza, S., Prasad, C.P., Srivastava, A., Gupta, S.D., and Ralhan, R. (2007) Promoter hypermethylation of p16INK4A, p14ARF, CyclinD2 and Slit2 in serum and tumor DNA from breast cancer patients. Life Sci. 80, 1873–1881.

    CAS  PubMed  Google Scholar 

  52. Taback, B., Giuliano, A.E., Lai, R., Hansen, N., Singer, F.R., Pantel, K., and Hoon, D.S. (2006) Epigenetic analysis of body fluids and tumor tissues: application of a comprehensive molecular assessment for early-stage breast cancer patients. Ann. N. Y. Acad. Sci. 1075, 211–221.

    CAS  PubMed  Google Scholar 

  53. Müller, H.M., Widschwendter, A., Fiegl, H., Ivarsson, L., Goebel, G., Perkmann, E., Marth, C., and Widschwendter, M. (2003) DNA methylation in serum of breast cancer patients: an independent prognostic marker. Cancer Res. 63, 7641–7645.

    PubMed  Google Scholar 

  54. Papadopoulou, E., Davilas, E., Sotiriou, V., Georgakopoulos, E., Georgakopoulou, S., Koliopanos, A., Aggelakis, F., Dardoufas, K., Agnanti, N.J., Karydas, I., and Nasioulas, G. (2006) Cell-free DNA and RNA in plasma as a new molecular marker for prostate and breast cancer. Ann. N. Y. Acad. Sci. 1075, 235–243.

    CAS  PubMed  Google Scholar 

  55. Zamagni, C., Martoni, A., Cacciari, N., Bellanova, B., Vecchi, F., and Pannuti, F. (1992) CA-549 serum levels in breast cancer monitoring. Int. J. Biol. Markers 7, 217–221.

    CAS  PubMed  Google Scholar 

  56. Rakha, E.A., Boyce, R.W., Abd El-Rehim, D., Kurien, T., Green, A.R., Paish, E.C., Robertson, J.F., and Ellis, I.O. (2005) Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer. Mod. Pathol. 18, 1295–1304.

    CAS  PubMed  Google Scholar 

  57. Giovanella, L., Ceriani, L., Giardina, G., Bardelli, D., Tanzi, F., and Garancini, S. (2002) Serum cytokeratin fragment 21.1 (CYFRA 21.1) as tumour marker for breast cancer: comparison with carbohydrate antigen 15.3 (CA 15.3) and carcinoembryonic antigen (CEA). Clin. Chem. Lab. Med. 40, 298–303.

    CAS  PubMed  Google Scholar 

  58. Eskelinen, M., Hippeläinen, M., Kettunen, J., Salmela, E., Penttilä, I., and Alhava, E. (1994) Clinical value of serum tumour markers TPA, TPS, TAG 12, CA 15-3 and MCA in breast cancer diagnosis; results from a prospective study. Anticancer Res. 14, 699–703.

    CAS  PubMed  Google Scholar 

  59. Slamon, D.J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., Fleming, T., Eierman, W., Wolter, J., Pegram, M., Baselga, J., and Norton, L. (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783–792.

    CAS  PubMed  Google Scholar 

  60. Kong, S.Y., Kang, J.H., Kwon, Y., Kang, H.S., Chung, K.W., Kang, S.H., Lee, D.H., Ro, J., and Lee, E.S. (2006) Serum HER-2 concentration in patients with primary breast cancer. J. Clin. Pathol. 59, 373–376.

    CAS  PubMed  Google Scholar 

  61. Quaranta, M., Daniele, A., Coviello, M., Savonarola, A., Abbate, I., Venneri, M.T., Paradiso, A., Stea, B., Zito, A., Labriola, A., and Schittulli, F. (2006) c-erbB-2 protein level in tissue and sera of breast cancer patients: a possibly useful clinical correlation. Tumori 92, 311–317.

    CAS  PubMed  Google Scholar 

  62. Imoto, S., Wada, N., Hasebe, T., Ochiai, A., and Kitoh, T. (2007) Serum c-erbB-2 protein is a useful marker for monitoring tumor recurrence of the breast. Int. J. Cancer 120, 357–361.

    CAS  PubMed  Google Scholar 

  63. Esteva, F.J., Cheli, C.D., Fritsche, H., Fornier, M., Slamon, D., Thiel, R.P., Luftner, D., and Ghani, F. (2005) Clinical utility of serum HER2/neu in monitoring and prediction of progression-free survival in metastatic breast cancer patients treated with trastuzumab-based therapies. Breast Cancer Res. 7, R436–443.

    CAS  PubMed  Google Scholar 

  64. Souder, C., Leitzel, K., Ali, S.M., Demers, L., Evans, D.B., Chaudri-Ross, H.A., Hackl, W., Hamer, P., Carney, W., and Lipton, A. (2006) Serum epidermal growth factor receptor/HER-2 predicts poor survival in patients with metastatic breast cancer. Cancer 107, 2337–2345.

    CAS  PubMed  Google Scholar 

  65. Bernstein, J.L., Godbold, J.H., Raptis, G., Watson, M.A., Levinson, B., Aaronson, S.A., and Fleming, T.P. (2005) Identification of mammaglobin as a novel serum marker for breast cancer. Clin. Cancer Res. 11, 6528–6535.

    CAS  PubMed  Google Scholar 

  66. Borgoño, C.A., Grass, L., Soosaipillai, A., Yousef, G.M., Petraki, C.D., Howarth, D.H., Fracchioli, S., Katsaros, D., and Diamandis, E.P. (2003) Human kallikrein 14: a new potential biomarker for ovarian and breast cancer. Cancer Res. 63, 9032–9041.

    PubMed  Google Scholar 

  67. Rodrigues, L.R., Teixeira, J.A., Schmitt, F.L., Paulsson, M., and Lindmark-Mänsson, H. The role of osteopontin in tumor progression and metastasis in breast cancer. (2007) Cancer Epidemiol. Biomarkers Prev. 16, 1087–1097.

    CAS  PubMed  Google Scholar 

  68. Balogh, G.A., Mailo, D.A., Corte, M.M., Roncoroni, P., Nardi, H., Vincent, E., Martinez, D., Cafasso, M.E., Frizza, A., Ponce, G., Vincent, E., Barutta, E., Lizarraga, P., Lizarraga, G., Monti, C., Paolillo, E., Vincent, R., Quatroquio, R., Grimi, C., Maturi, H., Aimale, M., Spinsanti, C., Montero, H., Santiago, J., Shulman, L., Rivadulla, M., Machiavelli, M., Salum, G., Cuevas, M.A., Picolini, J., Gentili, A., Gentili, R., and Mordoh, J. (2006) Mutant p53 protein in serum could be used as a molecular marker in human breast cancer. Int. J. Oncol. 28, 995–1002.

    CAS  PubMed  Google Scholar 

  69. Bianco, C., Strizzi, L., Mancino, M., Rehman, A., Hamada, S., Watanabe, K., De Luca, A., Jones, B., Balogh, G., Russo, J., Mailo, D., Palaia, R., D'Aiuto, G., Botti, G., Perrone, F., Salomon, D.S., and Normanno, N. (2006) Identification of cripto-1 as a novel serologic marker for breast and colon cancer. Clin. Cancer Res. 12, 5158–5164.

    CAS  PubMed  Google Scholar 

  70. Tworoger, S.S., Eliassen, A.H., Sluss, P., and Hankinson, S.E. (2007) A prospective study of plasma prolactin concentrations and risk of premenopausal and postmeno-pausal breast cancer. J. Clin. Oncol. 25, 1482–1488.

    CAS  PubMed  Google Scholar 

  71. Baglietto, L., English, D.R., Hopper, J.L., Morris, H.A., Tilley, W.D., and Giles, G.G. (2007) Circulating insulin-like growth factor-I and binding protein-3 and the risk of breast cancer. Cancer Epidemiol. Biomarkers Prev. 16, 763–768.

    CAS  PubMed  Google Scholar 

  72. Nguyen, M. (1997) Angiogenic factors as tumor markers. Invest. New Drug 15, 29–37.

    CAS  Google Scholar 

  73. Granato, A.M., Nanni, O., Falcini, F., Folli, S., Mosconi, G., De Paola, F., Medri, L., Amadori, D., and Volpi, A. (2004) Basic fibroblast growth factor and vascular endothelial growth factor serum levels in breast cancer patients and healthy women: useful as diagnostic tools? Breast Cancer Res. 6, R38–45.

    CAS  PubMed  Google Scholar 

  74. Bozcuk, H., Uslu, G., Samur, M., Yildiz, M., Ozben, T., Ozdoğan, M., Artaç, M., Altunbaş, H., Akan, I., and Sava ş , B. (2004) Tumour necrosis factor-alpha, interleukin-6, and fasting serum insulin correlate with clinical outcome in metastatic breast cancer patients treated with chemotherapy. Cytokine 27, 58–65.

    CAS  PubMed  Google Scholar 

  75. Eichbaum, M.H., de Rossi, T.M., Kaul, S., Bruckner, T., Schneeweiss, A., and Sohn, C. (2007) Serum levels of hepatocyte growth factor/scatter factor in patients with liver metastases from breast cancer. Tumour Biol. 28, 36–44.

    CAS  PubMed  Google Scholar 

  76. Dehqanzada, Z.A., Storrer, C.E., Hueman, M.T., Foley, R.J., Harris, K.A., Jama, Y.H., Shriver, C.D., Ponniah, S., and Peoples, G.E. (2007) Assessing serum cytokine profiles in breast cancer patients receiving a HER2/neu vaccine using Luminex technology. Oncol. Rep. 17 , 687–694.

    CAS  PubMed  Google Scholar 

  77. Caine, G.J., Stonelake, P.S., Lip, G.Y., and Blann, A.D. (2007) Changes in plasma vascular endothelial growth factor, angiopoietins, and their receptors following surgery for breast cancer. Cancer Lett. 248, 131– 136.

    CAS  PubMed  Google Scholar 

  78. Granato, A.M., Frassineti, G.L., Giovannini, N., Ballardini, M., Nanni, O., Maltoni, R., Amadori, D., and Volpi, A. (2006) Do serum angiogenic growth factors provide additional information to that of conventional markers in monitoring the course of metastatic breast cancer? Tumour Biol. 27, 302–308.

    CAS  PubMed  Google Scholar 

  79. Lipton, A., Ali, S.M., Leitzel, K., Demers, L., Evans, D.B., Hamer, P., Brown-Shimer, S., Pierce, K., and Carney, W. (2007) Elevated plasma tissue inhibitor of metallopro-teinase-1 level predicts decreased response and survival in metastatic breast cancer. Cancer 109 , 1933–1939.

    CAS  PubMed  Google Scholar 

  80. Kuvaja, P., Talvensaari-Mattila, A., Pääkkö, P., and Turpeenniemi-Hujanen, T. (2006) Low serum level of pro-matrix metalloproteinase 2 correlates with aggressive behavior in breast carcinoma. Hum. Pathol. 37, 1316– 1323.

    CAS  PubMed  Google Scholar 

  81. Sheen-Chen, S.M., Eng, H.L., Huang, C.C., and Chen, W.J. (2004) Serum levels of soluble E-selectin in women with breast cancer. Br. J. Surg. 91, 1578–1581.

    CAS  PubMed  Google Scholar 

  82. Disis, M.L., Pupa, S.M., Gralow, J.R., Dittadi, R., Menard, S., and Cheever, M.A. (1997) High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer. J. Clin. Oncol. 15 , 3363–3367.

    CAS  PubMed  Google Scholar 

  83. von Mensdorff-Pouilly, S., Gourevitch, M.M., Kenemans, P., Verstraeten, A.A., Litvinov, S.V., van Kamp, G.J., Meijer, S., Vermorken, J., and Hilgers, J. (1996) Humoral immune response to polymorphic epithelial mucin (MUC-1) in patients with benign and malignant breast tumours. Eur. J. Cancer 32A, 1325–1331.

    Google Scholar 

  84. Bachelot, T., Ratel, D., Menetrier-Caux, C., Wion, D., Blay, J.Y., and Berger, F. (2006) Autoantibodies to endostatin in patients with breast cancer: correlation to endostatin levels and clinical outcome. Br. J. Cancer 94, 1066–1070.

    CAS  PubMed  Google Scholar 

  85. Müller, M., Meyer, M., Schilling, T., Ulsperger, E., Lehnert, T., Zentgraf, H., Stremmel, W., Volkmann, M., and Galle, P.R. (2006) Testing for anti-p53 antibodies increases the diagnostic sensitivity of conventional tumor markers. Int. J. Oncol. 29, 973–980.

    PubMed  Google Scholar 

  86. Ferné ndez-Madrid, F., Tang, N., Alansari, H., Granda, J.L., Tait, L., Amirikia, K.C., Moroianu, M., Wang, X., and Karvonen, R.L. (2004) Autoantibodies to annexin XI-A and other autoantigens in the diagnosis of breast cancer. Cancer Res. 64, 5089–5096.

    Google Scholar 

  87. Harman, S.M., Gucciardo, F., Heward, C.B., Granstrom, P., Barclay-White, B., Rogers, L.W., and Ibarra, J.A. (2005) Discrimination of breast cancer by anti-malignin antibody serum test in women undergoing biopsy. Cancer Epidemiol. Biomarkers Prev. 14, 2310–2315.

    CAS  PubMed  Google Scholar 

  88. Minenkova, O., Pucci, A., Pavoni, E., De Tomassi, A., Fortugno, P., Gargano, N., Cianfriglia, M., Barca, S., De Placido, S., Martignetti, A., Felici, F., Cortese, R., and Monaci, P. (2003) Identification of tumor-associated antigens by screening phage-displayed human cDNA libraries with sera from tumor patients. Int. J. Cancer 106 , 534–544.

    CAS  PubMed  Google Scholar 

  89. Paik, S., Shak, S., Tang, G., Kim, C., Baker, J., Cronin, M., Baehner, F.L., Walker, M.G., Watson, D., Park, T., Hiller, W., Fisher, E., Wickerham, D.L., Bryant. J., and Wolmark, N. (2004) A multigene assay to predict recurrence of Tamoxifen-treated, node-negative breast cancer. N. Engl. J. Med. 351, 2817–2826.

    CAS  PubMed  Google Scholar 

  90. Buyse, M., Loi, S., van't Veer, L., Viale, G., Delorenzi, M., Glas, A.M., d'Assignies, M.S., Bergh, J., Lidereau, R., Ellis, P. , Harris, A., Bogaerts, J., Therasse, P. , Floore, A., Amakrane, M., Piette, F., Rutgers, E., Sotiriou, C., Cardoso, F., Piccart, M.J., and TRANSBIG Consortium. (2006) Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J. Natl. Cancer Inst. 98 , 1183–1192.

    CAS  PubMed  Google Scholar 

  91. Fan, C., Oh, D.S., Wessels, L., Weigelt, B., Nuyten, D.S., Nobel, A.B., van't Veer, L.J., and Perou, C.M. (2006) Concordance among gene-expression-based predictors for breast cancer. N. Engl. J. Med. 355, 560–569.

    CAS  PubMed  Google Scholar 

  92. Rui, Z., Jian-Guo, J., Yuan-Peng, T., Hai, P., and Bing-Gen, R. (2003) Use of serological proteomic methods to find biomarkers associated with breast cancer. Proteomics 3, 433–439.

    PubMed  Google Scholar 

  93. Li, J., Zhang, Z., Rosenzweig, J., Wang, Y.Y., and Chan, D.W. (2002) Proteomics and bioinformatics approaches for identification of serum biomarkers to detect breast cancer. Clin. Chem. 48, 1296–1304.

    CAS  PubMed  Google Scholar 

  94. Mathelin, C., Cromer, A., Wendling, C., Tomasetto, C., and Rio, M.C. (2006) Serum biomarkers for detection of breast cancers: A prospective study. Breast Cancer Res. Treat. 96, 83–90.

    CAS  PubMed  Google Scholar 

  95. Li, J., Orlandi, R., White, C.N., Rosenz-weig, J., Zhao, J., Seregni, E., Morelli, D., Yu, Y., Meng, X.Y., Zhang, Z., Davidson, N.E., Fung, E.T., and Chan, D.W. (2005) Independent validation of candidate breast cancer serum biomarkers identified by mass spectrometry. Clin. Chem. 51, 2229–2235.

    CAS  PubMed  Google Scholar 

  96. Shi, Q., Harris, L.N., Lu, X., Li, X., Hwang, J., Gentleman, R., Iglehart, J.D., and Miron, A. (2006) Declining plasma fibrinogen alpha fragment identifies HER2-positive breast cancer patients and reverts to normal levels after surgery. J. Proteome Res. 5 , 2947–2955.

    CAS  PubMed  Google Scholar 

  97. Lin, S.M. and Kibbe, W.A. (2005) Irrational exuberance in clinical proteomics. Clin. Cancer Res. 11, 7963–7964.

    PubMed  Google Scholar 

  98. Davis, M.A. and Hanash, S. (2006) High-throughput genomic technology in research and clinical management of breast cancer. Plasma-based proteomics in early detection and therapy. Breast Cancer Res. 8, 217.

    PubMed  Google Scholar 

  99. Kirmiz, C., Li, B., An, H.J., Clowers, B.H., Chew, H.K., Lam, K.S., Ferrige, A., Alecio, R., Borowsky, A.D., Sulaimon, S., Lebrilla, C.B., and Miyamoto, S. (2007) A serum glycomics approach to breast cancer biomarkers. Mol. Cell Proteomics 6, 43–55.

    CAS  PubMed  Google Scholar 

  100. Petrakis, N.L. (1993) Nipple aspirate fluid in epidemiologic studies of breast disease. Epidemiol. Rev. 15, 188–195.

    CAS  PubMed  Google Scholar 

  101. Brooks, M.N. (2003) Will the analysis of nipple fluid and breast cells be useful in the clinical care of the breast patient? Women's Oncol. Rev. 3, 179–186.

    Google Scholar 

  102. Liu, Y., Wang, J.L., Chang, H., Barsky, S.H., and Nguyen, M. (2000) Breast cancer diagnosis with nipple fluid bFGF. Lancet 356, 567.

    CAS  PubMed  Google Scholar 

  103. Sartippour, M.R., Zhang, L., Lu, M., Wang, H., and Brooks, M.N. (2005) Nipple fluid basic fibroblast growth factor in breast patients. Cancer Epidemiol. Biomarkers Prev. 4, 2995–2998.

    Google Scholar 

  104. Hsiung, R., Zhu, W., Klein, G., Qin, W., Rosenberg, A., Park, P., Rosato, E., and Sauter, E. (2002) High basic fibroblast growth factor levels in nipple aspirate fluid are correlated with breast cancer. Cancer J. 8, 308–310.

    Google Scholar 

  105. Black, M.H., Magklara, A., Obiezu, C., Levesque, M.A., Sutherland, D.J.A., Tindall, D.J., Young, C.Y.F., Sauter, E.R., and Diamandis, E.P. (2000) Expression of a prostate–associated protein, human glandular kallikrein (hK2), in breast tumours and in normal breast secretions. Br. J. Cancer 82, 361–367.

    CAS  PubMed  Google Scholar 

  106. Sauter, E.R., Welch, T., Magklara, A., Klein, G., and Diamandis, E.P. (2002) Ethnic variation in kallikrein expression in nipple aspirate fluid. Int. J. Cancer 100, 678–682.

    CAS  PubMed  Google Scholar 

  107. Kuerer, H.M., Thompson, P.A., Krishna-murthy, S., Fritsche, H.A., Marcy, S.M., Babiera, G.V., Singletary, S.E., Cristofanilli, M., Sneige, N., and Hunt, K.K. (2003) High and differential expression of HER-2/neu extracellular domain in bilateral ductal fluids from women with unilateral invasive breast cancer. Clin. Cancer Res. 9, 601–605.

    CAS  PubMed  Google Scholar 

  108. Sauter, E.R., Cher voneva, I., Diamandis, A., Khosravi, J.M., Litwin, S., and Diamandis, E.P. (2002) Prostate specific antigen and insulin like growth factor binding protein-3 in nipple aspirate fluid are associated with breast cancer. Cancer Detect. Prevent. 26, 149–157.

    CAS  PubMed  Google Scholar 

  109. Qin, W., Zhu, W., Wagner-Mann, C., Folk, W., and Sauter, E.R. (2003) Association of uPA, PAT-1, and uPAR in nipple aspirate fluid (NAF) with breast cancer. Cancer J. 9, 293–301.

    PubMed  Google Scholar 

  110. Alexander, H., Stegner, A.L., Wagner-Mann, C., Du Bois, G.C., Alexander, S., and Sauter, E.R. (2004) Proteomic analysis to identify breast cancer biomarkers in nipple aspirate fluid. Clin. Cancer Res. 10, 7500–7510.

    CAS  PubMed  Google Scholar 

  111. Li, J., Zhao, J., Yu, X., Lange, J., Kuerer, H., Krishnamurthy, S., Schilling, E., Khan, S.A., Sukumar, S., and Chan, D.W. (2005) Identification of biomarkers for breast cancer in nipple aspiration and ductal lavage fluid. Clin. Cancer Res. 11, 8312–8320.

    CAS  PubMed  Google Scholar 

  112. Mannello, F., Tonti, G.A., Pagliarani, S., Benedetti, S., Canestrari, F., Zhu, W., Qin, W., and Sauter, E.R. (2007) The 8-epimer of prostaglandin F(2alpha), a marker of lipid peroxidation and oxidative stress, is decreased in the nipple aspirate fluid of women with breast cancer. Int. J. Cancer 120, 1971–1976.

    CAS  PubMed  Google Scholar 

  113. Paweletz, C.P., Trock, B., Pennanen, M., Tsangaris, T., Magnant, C., Liotta, L.A., and Petricoin, E.F. 3rd. (2001) Proteomic patterns of nipple aspirate fluids obtained by SELDI-TOF: potential for new biomarkers to aid in the diagnosis of breast cancer. Dis. Markers 17, 301–307.

    CAS  PubMed  Google Scholar 

  114. Sauter, E.R., Zhu, W., Fan, X.J., Wassell, R.P., Chervoneva, I., and Du Bois, G.C. (2002) Proteomic analysis of nipple aspirate fluid to detect biologic markers of breast cancer. Br. J. Cancer 86, 1440–1443.

    CAS  PubMed  Google Scholar 

  115. Pawlik, T.M., Hawke, D.H., Liu, Y., Krishna-murthy, S., Fritsche, H., Hunt, K.K., and Kuerer, H.M. (2006) Proteomic analysis of nipple aspirate fluid from women with early-stage breast cancer using isotope-coded affinity tags and tandem mass spectrometry reveals differential expression of vitamin D binding protein. BMC Cancer 6, 68.

    PubMed  Google Scholar 

  116. He, J., Gornbein, J., Shen, D., Lu, M., Rovai, L.E., Shau, H., Katz, J., Whitelegge, J.P., Faull, K.F., and Chang, H.R. (2007) Detection of breast cancer biomarkers in nipple aspirate fluid by SELDI-TOF and their identification by combined liquid chro-matography-tandem mass spectrometry. Int. J. Oncol. 30, 145–154.

    CAS  PubMed  Google Scholar 

  117. Sauter, E.R., Wagner-Mann, C., Ehya, H., and Klein-Szanto, A. (2007) Biologic markers of breast cancer in nipple aspirate fluid and nipple discharge are associated with clinical findings. Cancer Detect. Prev. 31, 50–58.

    PubMed  Google Scholar 

  118. Dooley, W.C., Ljung, B.M., Veronesi, U., Cazzaniga, M., Elledge, R.M., O'shaughnessy, J.A., Kuerer, H.M., Hung, D.T., Khan, S.A., Phillips, R.F., Ganz, P.A., Euhus, D.M., Esserman, L.J., Haffty, B.G., King, B.L., Kelley, M.C., Anderson, M.M., Schmit, P.J., Clark, R.R., Kass, F.C., Anderson, B.O., Troyan, S.L., Arias, R.D., Quiring, J.N., Love, S.M., Page, D.L., and King, E.B. (2001) Ductal lavage for detection of cellular atypia in women at high risk for breast cancer. J. Natl. Cancer Inst. 93, 1624–1632.

    CAS  PubMed  Google Scholar 

  119. Khan, S.A., Wiley, E.L., Rodriguez, N., Baird, C., Ramakrishnan, R., Nayar, R., Bryk, M., Bethke, K.B., Staradub, V.L., Wolfman, J., Rademaker, A., Ljung, B.M., and Morrow, M. (2004) Ductal lavage finding in women with known breast cancer undergoing mastectomy. J. Natl. Cancer Inst. 96 , 1510–1517.

    PubMed  Google Scholar 

  120. Ozanne, E.M. and Esserman, L.J. (2004) Evaluation of breast cancer risk assessment techniques: a cost effectiveness analysis. Cancer Epidemiol. Biomarker Prev. 13, 2043–2052.

    CAS  Google Scholar 

  121. Wrensch, M.R., Petrakis, N.L., King, E.B., Lee, M.M., and Miike, R. (1993) Breast cancer risk associated with abnormal cytology in nipple aspirates of breast fluid and prior history of breast biopsy. Am. J. Epidemiol. 37, 829–833.

    Google Scholar 

  122. Wrensch, M.R., Petrakis, N.L., Miike, R., King, E.B., Chew, K., Neuhaus, J., Lee, M.M., and Rhys, M. (2001) Breast cancer risk in women with abnormal cytology in nipple aspirates of breast fluid. J. Natl. Cancer Inst. 93, 1791–1798.

    CAS  PubMed  Google Scholar 

  123. Fabian, C.J., Kimler, B.F., Zalles, C.M., Klemp, J.R., Kamel, S., Zeiger, S., and Mayo, M.S. (2000) Short-term breast cancer prediction by random periareolar fine-needle aspiration cytology and the gail risk model. J. Natl. Cancer Inst. 92, 1217–1227.

    CAS  PubMed  Google Scholar 

  124. Motomura, K., Koyama, H., Noguchi, S., Inaji, H., and Azuma, C. (1995) Detection of c-erbB-2 gene amplification in nipple discharge by means of polymerase chain reaction. Breast Cancer Res. Treat. 33, 89–92.

    CAS  PubMed  Google Scholar 

  125. King, B.L., Tsai, S.C., Gr yga, M.E., D'Aquila, T.G., Seelig, S.A., Morrison, L.E., Jacobson, K.K.B., Legator, M.S., Ward, D.C., Rimm, D.L., and Phillips, R.F. (2003) Detection of chromosomal instability in paried breast surgery and ductal lavage specimens by interphase fluorescence in situ hybridization. Clin. Cancer Res. 9, 1509–1516.

    CAS  PubMed  Google Scholar 

  126. Zhu, W., Qin, W., Ehya, H., Lininger, J., and Sauter, E. (2003) Microsatellite changes in nipple aspirate fluid and breast tissue from women with breast carcinoma or its precursors. Clin. Cancer Res. 9, 3029–3033.

    CAS  PubMed  Google Scholar 

  127. Rao, J.Y., Apple, S.K., Jin, T.S., Lin, S., Nieberg, R.K., and Hirtschowitz, S.L. (2000) Comparative polymerase chain reaction analysis of c-myc amplification on archival breast fine needle aspiration materials. Cancer Epidemiol. Biomarkers Prev. 9, 175–179.

    CAS  PubMed  Google Scholar 

  128. Heselmeyer-Haddad, K., Chaudhri, N., Stoltzfus, P., Cheng, J.C., Wilber, K., Morrison, L., Auer, G., and Ried, T. (2002) Detection of chromosomal aneuploidies and gene copy number changes in fine needle aspirates is a specific, sensitive, and objective genetic test for the diagnosis of breast cancer. Cancer Res. 62, 2365–2369.

    CAS  PubMed  Google Scholar 

  129. Wu, J.T., Zhang, P., and Bentz, J.S. (2000) Quantification of HER2 oncoprotein in fine-needle aspirates of the breast. Ann. Clin. Lab Sci. 30, 49–56.

    CAS  PubMed  Google Scholar 

  130. Ball, H.M., Hupp, T.R., Ziyaie, D., Purdie, C.A., Kernohan, N.M., and Thompson, A.M. (2001) Differential p53 protein expression in breast cancer fine needle aspirates: the potential for in vivo monitoring. Br. J. Cancer 85, 1102–1105.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Brooks, M. (2009). Breast Cancer Screening and Biomarkers. In: Verma, M. (eds) Cancer Epidemiology. Methods in Molecular Biology, vol 472. Humana Press. https://doi.org/10.1007/978-1-60327-492-0_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-492-0_13

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60327-491-3

  • Online ISBN: 978-1-60327-492-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics