| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Pathology [M. F. P., G. H., J. A. U., M. M.] and Preventive Medicine, [M. C. Pi.], University of Southern California School of Medicine, Los Angeles, California 90033; Division of Hematology-Oncology, UCLA, School of Medicine, Los Angeles, California 90024-16-8 [V. R. C., D. J. S.]; Misericordia Hospital and Cross Cancer Institute, Edmonton, Alberta, Canada [J. D., M. C. Pa.]; Division of Clinical Chemistry, Vancouver General Hospital, Vancouver, British Columbia, Canada [W. G.] Berlex Biosciences, Alameda, California [M. S., R. A.]
The HER-2/neu proto-oncogene (also known as c-ceb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods.
In this report we present data from a study of HER-2/neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced recurrent disease (relapsed cases) 105 were matched with 105 women with no recurrence (disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/neu expression in archival tissue blocks from both relapsed cases and their matched disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens.
Quantitation of the amount of HER-2/neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens. Breast cancer cells with no overexpression of HER-2/neu had an average oncoprotein content of 0.18 ± 0.02 (SE) pg/cell, whereas the content of those with overexpression was as follows: 2.01 ± 0.73 pg/cell in cancers with overexpression but no amplification; 2.60 ± 0.47 pg/cell in cancers with 2 to 5-fold amplification and overexpression; and 3.38 ± 0.29 pg/cell in cancers with more than 5-fold amplification and overexpression. HER-2/neu overexpression was identified in 41 of 105 relapsed cases and in 21 of 105 matched disease-free controls. The risk of developing recurrent disease in node-negative women with any level of HER-2/neu overexpression was 3.0 times that of women whose breast cancer lacked overexpression while the group of patients with high overexpression had a risk of recurrence 9.5 times greater than those whose breast cancers had normal expression (P = 0.0001). Analysis of various subgroups showed significantly increased risks in pre- and postmenopausal women as well as in women with estrogen receptor-negative and small (T1A) breast cancers indicating the increased risk of recurrence extended across several subgroups of node-negative breast cancer patients.
Our results demonstrate that HER-2/neu overexpression is an independent indicator of increased risk of developing recurrent disease in women with node-negative breast cancer. Although frozen tissue is optimal for analysis, formalin-fixed, paraffin-embedded tissue can yield meaningful results when reagents of sufficient sensitivity and specificity are used. Finally, the quantitative amount of oncoprotein in tumor cells can be determined using immunohistochemistry in conjunction with computerized image analysis.
1 Supported in part by grants from the National Cancer Institute (CA48780, CA14089, CA36827, and CA50589), National Cancer Institute of Canada, American Cancer Society (IN-21-29/003 and PDT-411), Medical Research Council of Canada, Alberta Cancer Board Research Initiative Program, The Vance Wall Foundation, Montclair, NJ, and the Revlon/UCLA Women's Cancer Research Program. M. C. Pa. is a Medical Scientist of the Alberta Heritage Foundation for Medical Research. V. R. C. is supported by a Fellowship from the Concern Foundation. D. J. S. has a Faculty Research Award from the American Cancer Society.
2 To whom requests for reprints should be addressed.
Received 10/26/92. Accepted 8/11/93.
This article has been cited by other articles:
|
|
 |
|
  Y. Xiao, X. Gao, S. Maragh, W. G. Telford, and A. Tona Cell Lines as Candidate Reference Materials for Quality Control of ERBB2 Amplification and Expression Assays in Breast Cancer Clin. Chem., July 1, 2009; 55(7): 1307 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C.F. Dijkers, J. G.W. Kosterink, A. P. Rademaker, L. R. Perk, G. A.M.S. van Dongen, J. Bart, J. R. de Jong, E. G.E. de Vries, and M. N. Lub-de Hooge Development and Characterization of Clinical-Grade 89Zr-Trastuzumab for HER2/neu ImmunoPET Imaging J. Nucl. Med., June 1, 2009; 50(6): 974 - 981. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Neal, J. Yao, W. Yang, X. Zhou, N. T. Nguyen, J. Lu, C. G. Danes, H. Guo, K.-H. Lan, J. Ensor, et al. 14-3-3{zeta} Overexpression Defines High Risk for Breast Cancer Recurrence and Promotes Cancer Cell Survival Cancer Res., April 15, 2009; 69(8): 3425 - 3432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Ross, E. A. Slodkowska, W. F. Symmans, L. Pusztai, P. M. Ravdin, and G. N. Hortobagyi The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti-HER-2 Therapy and Personalized Medicine Oncologist, April 1, 2009; 14(4): 320 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Sauter, J. Lee, J. M.S. Bartlett, D. J. Slamon, and M. F. Press Guidelines for Human Epidermal Growth Factor Receptor 2 Testing: Biologic and Methodologic Considerations J. Clin. Oncol., March 10, 2009; 27(8): 1323 - 1333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Press, R. S. Finn, D. Cameron, A. Di Leo, C. E. Geyer, I. E. Villalobos, A. Santiago, R. Guzman, A. Gasparyan, Y. Ma, et al. HER-2 Gene Amplification, HER-2 and Epidermal Growth Factor Receptor mRNA and Protein Expression, and Lapatinib Efficacy in Women with Metastatic Breast Cancer Clin. Cancer Res., December 1, 2008; 14(23): 7861 - 7870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C L Hyun, H E Lee, K S Kim, S-W Kim, J H Kim, G Choe, and S Y Park The effect of chromosome 17 polysomy on HER-2/neu status in breast cancer J. Clin. Pathol., March 1, 2008; 61(3): 317 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Moon, G. Park, K. Han, C.-S. Kang, and W. Lee Mouse Spleen Tissue as a Staining Intensity Reference for Immunohistochemistry Ann. Clin. Lab. Sci., January 1, 2008; 38(3): 215 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Limentani, A. M. Brufsky, J. K. Erban, M. Jahanzeb, and D. Lewis Phase II Study of Neoadjuvant Docetaxel, Vinorelbine, and Trastuzumab Followed by Surgery and Adjuvant Doxorubicin Plus Cyclophosphamide in Women With Human Epidermal Growth Factor Receptor 2-Overexpressing Locally Advanced Breast Cancer J. Clin. Oncol., April 1, 2007; 25(10): 1232 - 1238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Wolff, M. E. H. Hammond, J. N. Schwartz, K. L. Hagerty, D. C. Allred, R. J. Cote, M. Dowsett, P. L. Fitzgibbons, W. M. Hanna, A. Langer, et al. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer J. Clin. Oncol., January 1, 2007; 25(1): 118 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yen, Z. Cao, X. Wu, E. R.Q. Ingalla, C. Baron, L. J.T. Young, J. P. Gregg, R. D. Cardiff, A. D. Borowsky, C. Sweeney, et al. Loss of Nrdp1 Enhances ErbB2/ErbB3-Dependent Breast Tumor Cell Growth Cancer Res., December 1, 2006; 66(23): 11279 - 11286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Shin, E. Hyjek, E. Early, and D. M. Knowles Intratumoral Heterogeneity of HER-2/neu in Invasive Mammary Carcinomas Using Fluorescence In-Situ Hybridization and Tissue Microarray International Journal of Surgical Pathology, October 1, 2006; 14(4): 279 - 284. [Abstract] [PDF]
|
|
|
|
|
|
N. Robert, B. Leyland-Jones, L. Asmar, R. Belt, D. Ilegbodu, D. Loesch, R. Raju, E. Valentine, R. Sayre, M. Cobleigh, et al. Randomized Phase III Study of Trastuzumab, Paclitaxel, and Carboplatin Compared With Trastuzumab and Paclitaxel in Women With HER-2-Overexpressing Metastatic Breast Cancer J. Clin. Oncol., June 20, 2006; 24(18): 2786 - 2792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Smith-Jones, D. Solit, F. Afroze, N. Rosen, and S. M. Larson Early Tumor Response to Hsp90 Therapy Using HER2 PET: Comparison with 18F-FDG PET J. Nucl. Med., May 1, 2006; 47(5): 793 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Xue, F. Liang, R. Mahmood, M. Vuolo, J. Wyckoff, H. Qian, K.-L. Tsai, M. Kim, J. Locker, Z.-Y. Zhang, et al. ErbB3-Dependent Motility and Intravasation in Breast Cancer Metastasis Cancer Res., February 1, 2006; 66(3): 1418 - 1426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R Ainsworth, J M S Bartlett, J J Going, E A Mallon, A Forsyth, J Richmond, W Angerson, A Watters, and B Dunne IHC for Her2 with CBE356 antibody is a more accurate predictor of Her2 gene amplification by FISH than HercepTestTM in breast carcinoma J. Clin. Pathol., October 1, 2005; 58(10): 1086 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Press, G. Sauter, L. Bernstein, I. E. Villalobos, M. Mirlacher, J.-Y. Zhou, R. Wardeh, Y.-T. Li, R. Guzman, Y. Ma, et al. Diagnostic Evaluation of HER-2 as a Molecular Target: An Assessment of Accuracy and Reproducibility of Laboratory Testing in Large, Prospective, Randomized Clinical Trials Clin. Cancer Res., September 15, 2005; 11(18): 6598 - 6607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Norum, T. Risberg, and J. A. Olsen A monoclonal antibody against HER-2 (trastuzumab) for metastatic breast cancer: a model-based cost-effectiveness analysis Ann. Onc., June 1, 2005; 16(6): 909 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M.M. Lahorte, K. Bacher, I. Burvenich, E. D. Coene, C. Cuvelier, C. De Potter, H. Thierens, C. Van de Wiele, R. A. Dierckx, and G. Slegers Radiolabeling, Biodistribution, and Dosimetry of 123I-mAb 14C5: A New mAb for Radioimmunodetection of Tumor Growth and Metastasis In Vivo J. Nucl. Med., June 1, 2004; 45(6): 1065 - 1073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Benoit, A. Chariot, L. Delacroix, V. Deregowski, N. Jacobs, M.-P. Merville, and V. Bours Caspase-8-Dependent HER-2 Cleavage in Response to Tumor Necrosis Factor {alpha} Stimulation Is Counteracted by Nuclear Factor {kappa}B through c-FLIP-L Expression Cancer Res., April 15, 2004; 64(8): 2684 - 2691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Ross, J. A. Fletcher, K. J. Bloom, G. P. Linette, J. Stec, W. F. Symmans, L. Pusztai, and G. N. Hortobagyi Targeted Therapy in Breast Cancer: The HER-2/neu Gene and Protein Mol. Cell. Proteomics, April 1, 2004; 3(4): 379 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Elkin, M. C. Weinstein, E. P. Winer, K. M. Kuntz, S. J. Schnitt, and J. C. Weeks HER-2 Testing and Trastuzumab Therapy for Metastatic Breast Cancer: A Cost-Effectiveness Analysis J. Clin. Oncol., March 1, 2004; 22(5): 854 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Millson, A. Suli, L. Hartung, S. Kunitake, A. Bennett, M. C. L. Nordberg, W. Hanna, C. T. Wittwer, A. Seth, and E. Lyon Comparison of Two Quantitative Polymerase Chain Reaction Methods for Detecting HER2/neu Amplification J. Mol. Diagn., August 1, 2003; 5(3): 184 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Ross, J. A. Fletcher, G. P. Linette, J. Stec, E. Clark, M. Ayers, W. F. Symmans, L. Pusztai, and K. J. Bloom The HER-2/neu Gene and Protein in Breast Cancer 2003: Biomarker and Target of Therapy Oncologist, August 1, 2003; 8(4): 307 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Konecny, G. Pauletti, M. Pegram, M. Untch, S. Dandekar, Z. Aguilar, C. Wilson, H.-M. Rong, I. Bauerfeind, M. Felber, et al. Quantitative Association Between HER-2/neu and Steroid Hormone Receptors in Hormone Receptor-Positive Primary Breast Cancer J Natl Cancer Inst, January 15, 2003; 95(2): 142 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Press, D. J. Slamon, K. J. Flom, J. Park, J.-Y. Zhou, and L. Bernstein Evaluation of HER-2/neu Gene Amplification and Overexpression: Comparison of Frequently Used Assay Methods in a Molecularly Characterized Cohort of Breast Cancer Specimens J. Clin. Oncol., July 15, 2002; 20(14): 3095 - 3105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Osoba, D. J. Slamon, M. Burchmore, and M. Murphy Effects on Quality of Life of Combined Trastuzumab and Chemotherapy in Women With Metastatic Breast Cancer J. Clin. Oncol., July 15, 2002; 20(14): 3106 - 3113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Ellis, A. Coop, B. Singh, L. Mauriac, A. Llombert-Cussac, F. Janicke, W. R. Miller, D. B. Evans, M. Dugan, C. Brady, et al. Letrozole Is More Effective Neoadjuvant Endocrine Therapy Than Tamoxifen for ErbB-1- and/or ErbB-2-Positive, Estrogen Receptor-Positive Primary Breast Cancer: Evidence From a Phase III Randomized Trial J. Clin. Oncol., September 15, 2001; 19(18): 3808 - 3816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yamauchi, V. Stearns, and D. F. Hayes When Is a Tumor Marker Ready for Prime Time? A Case Study of c-erbB-2 as a Predictive Factor in Breast Cancer J. Clin. Oncol., April 15, 2001; 19(8): 2334 - 2356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Slamon, B. Leyland-Jones, S. Shak, H. Fuchs, V. Paton, A. Bajamonde, T. Fleming, W. Eiermann, J. Wolter, M. Pegram, et al. Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2 N. Engl. J. Med., March 15, 2001; 344(11): 783 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Summerhayes Trastuzumab in the treatment of HER2 positive breast cancer Journal of Oncology Pharmacy Practice, March 1, 2001; 7(1): 9 - 25. [Abstract] [PDF]
|
|
|
|
|
|
I. Hellström, G. Goodman, J. Pullman, Y. Yang, and K. E. Hellström Overexpression of HER-2 in Ovarian Carcinomas Cancer Res., March 1, 2001; 61(6): 2420 - 2423. [Abstract] [Full Text]
|
|
|
|
|
|
M B Pereira, A J Dias, C A Reis, and F C Schmitt Immunohistochemical study of the expression of MUC5AC and MUC6 in breast carcinomas and adjacent breast tissues J. Clin. Pathol., March 1, 2001; 54(3): 210 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pauletti, S. Dandekar, H. Rong, L. Ramos, H. Peng, R. Seshadri, and D. J. Slamon Assessment of Methods for Tissue-Based Detection of the HER-2/neu Alteration in Human Breast Cancer: A Direct Comparison of Fluorescence In Situ Hybridization and Immunohistochemistry J. Clin. Oncol., November 1, 2000; 18(21): 3651 - 3664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Dela Cruz, K. R. Trinh, S. L. Morrison, and M. L. Penichet Recombinant Anti-Human HER2/neu IgG3-(GM-CSF) Fusion Protein Retains Antigen Specificity and Cytokine Function and Demonstrates Antitumor Activity J. Immunol., November 1, 2000; 165(9): 5112 - 5121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Lane, I. Beuvink, A. B. Motoyama, J. M. Daly, R. M. Neve, and N. E. Hynes ErbB2 Potentiates Breast Tumor Proliferation through Modulation of p27Kip1-Cdk2 Complex Formation: Receptor Overexpression Does Not Determine Growth Dependency Mol. Cell. Biol., May 1, 2000; 20(9): 3210 - 3223. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. Bai, B. Connolly, M. L. Metzker, C. A. Hilliard, X. Liu, V. Sandig, A. Soderman, S. M. Galloway, Q. Liu, C. P. Austin, et al. Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster PNAS, February 1, 2000; 97(3): 1230 - 1235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Stark, B. S. Hulka, S. Joens, D. Novotny, A. D. Thor, L. E. Wold, M. J. Schell, L. J. Melton III, E. T. Liu, and K. Conway HER-2/neu Amplification in Benign Breast Disease and the Risk of Subsequent Breast Cancer J. Clin. Oncol., January 14, 2000; 18(2): 267 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-R. N. ZEKRI, A. A. BAHNASSY, S. M. SHAARAWY, O. A. MANSOUR, M. A. MADUAR, H. M. KHALED, and O. EL-AHMADI Hepatitis C virus genotyping in relation to neu-oncoprotein overexpression and the development of hepatocellular carcinoma J. Med. Microbiol., January 1, 2000; 49(1): 89 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Bacus, C. W. Boone, J. V. Bacus, M. Follen, G. J. Kelloff, V. Kagan, and S. M. Lippman Image Morphometric Nuclear Grading of Intraepithelial Neoplastic Lesions with Applications to Cancer Chemoprevention Trials Cancer Epidemiol. Biomarkers Prev., December 1, 1999; 8(12): 1087 - 1094. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. E. Shackney, C. A. Smith, A. Pollice, M. Levitt, J. A. Magovern, R. J. Wiechmann, J. Silverman, L. Sweeney, and R. J. Landreneau GENETIC EVOLUTIONARY STAGING OF EARLY NON-SMALL CELL LUNG CANCER: THE P53 -> HER-2/NEU -> ras SEQUENCE J. Thorac. Cardiovasc. Surg., August 1, 1999; 118(2): 259 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Jacobs, A. M. Gown, H. Yaziji, M. J. Barnes, and S. J. Schnitt Comparison of Fluorescence In Situ Hybridization and Immunohistochemistry for the Evaluation of HER-2/neu in Breast Cancer J. Clin. Oncol., July 1, 1999; 17(7): 1974 - 1974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.R.J. Evans and S.B. Kaye Vaccine therapy for cancer—fact or fiction? QJM, June 1, 1999; 92(6): 299 - 307. [Full Text] [PDF]
|
|
|
|
|
|
J. S. Ross and J. A. Fletcher The HER-2/neu Oncogene in Breast Cancer: Prognostic Factor, Predictive Factor, and Target for Therapy Oncologist, August 1, 1998; 3(4): 237 - 252. [Abstract] [Full Text]
|
|
|
|
 |
|
 W. M. Pardridge, J. Buciak, J. Yang, and D. Wu Enhanced Endocytosis in Cultured Human Breast Carcinoma Cells and In Vivo Biodistribution in Rats of a Humanized Monoclonal Antibody after Cationization of the Protein J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 548 - 554. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. N. Beckhardt, N. Kiyokawa, L. Xi, T.-J. Liu, M.-C. Hung, A. K. El-Naggar, H.-Z. Zhang, and G. L. Clayman HER-2/neu Oncogene Characterization in Head and Neck Squamous Cell Carcinoma Arch Otolaryngol Head Neck Surg, November 1, 1995; 121(11): 1265 - 1270. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Yamauchi, N. Yamauchi, K. Ueki, T. Sugiyama, H. Waki, H. Miki, K. Tobe, S. Matsuda, T. Tsushima, T. Yamamoto, et al. Constitutive Tyrosine Phosphorylation of ErbB-2 via Jak2 by Autocrine Secretion of Prolactin in Human Breast Cancer J. Biol. Chem., October 20, 2000; 275(43): 33937 - 33944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. H. Donovan, A. Milic, and J. M. Slingerland Constitutive MEK/MAPK Activation Leads to p27Kip1 Deregulation and Antiestrogen Resistance in Human Breast Cancer Cells J. Biol. Chem., October 26, 2001; 276(44): 40888 - 40895. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
