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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
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.
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.
American Cancer Society. (2007) Cancer facts & figures 2007. Atlanta: American Cancer Society.
Shapiro, S. (1997) Periodic screening for breast cancer: the HIP Randomized Controlled Trial. Health Insurance Plan. J. Natl. Cancer Inst. Monogr. 22 , 27 – 30.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Hall, F.M. (2007) Breast imaging and computer-aided detection. Engl. J. Med. 356, 1464–1466.
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.
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.
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.
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.
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.
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.
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.
Duffy, M.J. (2006) Serum tumor markers in breast cancer: are they of clinical value? Clin. Chem. 52, 345–351.
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.
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.
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.
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.
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.
Müller, V., Hayes, D.F., and Pantel, K. (2006) Recent translational research: circulating tumor cells in breast cancer patients. Breast Cancer Res. 8, 110.
Lacroix, M. (2006) Significance, detection and markers of disseminated breast cancer cells. Endocr. Relat. Cancer 13, 1033–1067.
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.
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.
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.
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.
Levenson, V.V. (2007) Biomarkers for early detection of breast cancer: what, when, and where? Biochim. Biophys. Acta. 1770, 847–856.
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.
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.
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.
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.
Herman, J.G. and Baylin, S.B. (2003) Gene silencing in cancer in association with promoter hypermethylation. N. Engl. J. Med. 349, 2042–2054.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Nguyen, M. (1997) Angiogenic factors as tumor markers. Invest. New Drug 15, 29–37.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Lin, S.M. and Kibbe, W.A. (2005) Irrational exuberance in clinical proteomics. Clin. Cancer Res. 11, 7963–7964.
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.
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.
Petrakis, N.L. (1993) Nipple aspirate fluid in epidemiologic studies of breast disease. Epidemiol. Rev. 15, 188–195.
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.
Liu, Y., Wang, J.L., Chang, H., Barsky, S.H., and Nguyen, M. (2000) Breast cancer diagnosis with nipple fluid bFGF. Lancet 356, 567.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights 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