FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 348:2339-2347 June 5, 2003 Number 23 Next

	Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

	Full Text PDF PDA Full Text Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

Despite years of intensive study and substantial progress in understanding susceptibility to breast and ovarian cancer, these diseases remain important causes of death in women. However, several recent critical advances — sequencing of the human genome and the development of high-throughput techniques for identifying DNA-sequence variants, changes in copy numbers, and global expression profiles — have dramatically accelerated the pace of research aimed at preventing and curing these diseases. We review some of the important discoveries in the genetics of breast and ovarian cancer, ongoing studies to isolate additional susceptibility genes, and early work on molecular profiling involving microarrays.

Susceptibility to Breast and Ovarian Cancer

In . . . [Full Text of this Article]

Identification of Genes That Increase Susceptibility to Breast and Ovarian Cancer

Identification of High-Penetrance Genes

BRCA3 and beyond

Use of the Human Genome Sequence to Identify Low-Penetrance Genes

Whole-Genome Approaches to the Analysis of Breast and Ovarian Cancer

Clinical Management of Inherited Susceptibility to Breast and Ovarian Cancer

Summary

Source Information

From the Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom (R.W.); and the University of Pennsylvania, Philadelphia (B.L.W.).

Related Letters:

Breast-Cancer Genomics
Friedenson B., Piver M. S., Weber B. L., Wooster R.
Extract | Full Text | PDF  
N Engl J Med 2003; 349:910-911, Aug 28, 2003. Correspondence

This article has been cited by other articles:

• Ludwig, A. H., Murawska, M., Panek, G., Timorek, A., Kupryjanczyk, J. (2009). Androgen, progesterone, and FSH receptor polymorphisms in ovarian cancer risk and outcome. Endocr Relat Cancer 16: 1005-1016 [Abstract] [Full Text]  
• Fu, P., Dowlati, A., Schluchter, M. (2009). Comparison of Power Between Randomized Discontinuation Design and Upfront Randomization Design on Progression-Free Survival. JCO 27: 4135-4141 [Abstract] [Full Text]  
• Fong, P. C., Boss, D. S., Yap, T. A., Tutt, A., Wu, P., Mergui-Roelvink, M., Mortimer, P., Swaisland, H., Lau, A., O'Connor, M. J., Ashworth, A., Carmichael, J., Kaye, S. B., Schellens, J. H.M., de Bono, J. S. (2009). Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers. NEJM 361: 123-134 [Abstract] [Full Text]  
• Ghosh, S., Choudary, A., Ghosh, S., Musi, N., Hu, Y., Li, R. (2009). IKK{beta} Mediates Cell Shape-Induced Aromatase Expression and Estrogen Biosynthesis in Adipose Stromal Cells. Mol. Endocrinol. 23: 662-670 [Abstract] [Full Text]  
• BOGAARD, K., JOHNSON, M. (2009). Genetics and Genomic Medicine. radtech 80: 318-335 [Abstract] [Full Text]  
• Reid, L. J., Shakya, R., Modi, A. P., Lokshin, M., Cheng, J.-T., Jasin, M., Baer, R., Ludwig, T. (2008). E3 ligase activity of BRCA1 is not essential for mammalian cell viability or homology-directed repair of double-strand DNA breaks. Proc. Natl. Acad. Sci. USA 105: 20876-20881 [Abstract] [Full Text]  
• Ashworth, A. (2008). Drug Resistance Caused by Reversion Mutation. Cancer Res. 68: 10021-10023 [Abstract] [Full Text]  
• Newman, W. G., Hadfield, K. D., Latif, A., Roberts, S. A., Shenton, A., McHague, C., Lalloo, F., Howell, S., Evans, D. G. (2008). Impaired Tamoxifen Metabolism Reduces Survival in Familial Breast Cancer Patients. Clin. Cancer Res. 14: 5913-5918 [Abstract] [Full Text]  
• Chen, P., Liang, J., Wang, Z., Zhou, X., Chen, L., Li, M., Xie, D., Hu, Z., Shen, H., Wang, H. (2008). Association of Common PALB2 Polymorphisms with Breast Cancer Risk: A Case-Control Study. Clin. Cancer Res. 14: 5931-5937 [Abstract] [Full Text]  
• Ashworth, A. (2008). A Synthetic Lethal Therapeutic Approach: Poly(ADP) Ribose Polymerase Inhibitors for the Treatment of Cancers Deficient in DNA Double-Strand Break Repair. JCO 26: 3785-3790 [Abstract] [Full Text]  
• Shakya, R., Szabolcs, M., McCarthy, E., Ospina, E., Basso, K., Nandula, S., Murty, V., Baer, R., Ludwig, T. (2008). The basal-like mammary carcinomas induced by Brca1 or Bard1 inactivation implicate the BRCA1/BARD1 heterodimer in tumor suppression. Proc. Natl. Acad. Sci. USA 105: 7040-7045 [Abstract] [Full Text]  
• Kauff, N. D., Domchek, S. M., Friebel, T. M., Robson, M. E., Lee, J., Garber, J. E., Isaacs, C., Evans, D. G., Lynch, H., Eeles, R. A., Neuhausen, S. L., Daly, M. B., Matloff, E., Blum, J. L., Sabbatini, P., Barakat, R. R., Hudis, C., Norton, L., Offit, K., Rebbeck, T. R. (2008). Risk-Reducing Salpingo-Oophorectomy for the Prevention of BRCA1- and BRCA2-Associated Breast and Gynecologic Cancer: A Multicenter, Prospective Study. JCO 26: 1331-1337 [Abstract] [Full Text]  
• Gehlert, S., Sohmer, D., Sacks, T., Mininger, C., McClintock, M., Olopade, O. (2008). Targeting Health Disparities: A Model Linking Upstream Determinants To Downstream Interventions. Health Aff (Millwood) 27: 339-349 [Abstract] [Full Text]  
• Martin, L. P., Hamilton, T. C., Schilder, R. J. (2008). Platinum Resistance: The Role of DNA Repair Pathways. Clin. Cancer Res. 14: 1291-1295 [Abstract] [Full Text]  
• Laufer, M., Nandula, S. V., Modi, A. P., Wang, S., Jasin, M., Murty, V. V. V. S., Ludwig, T., Baer, R. (2007). Structural Requirements for the BARD1 Tumor Suppressor in Chromosomal Stability and Homology-directed DNA Repair. J. Biol. Chem. 282: 34325-34333 [Abstract] [Full Text]  
• Zhang, L., Huang, J., Yang, N., Greshock, J., Liang, S., Hasegawa, K., Giannakakis, A., Poulos, N., O'Brien-Jenkins, A., Katsaros, D., Butzow, R., Weber, B. L., Coukos, G. (2007). Integrative Genomic Analysis of Phosphatidylinositol 3'-Kinase Family Identifies PIK3R3 as a Potential Therapeutic Target in Epithelial Ovarian Cancer. Clin. Cancer Res. 13: 5314-5321 [Abstract] [Full Text]  
• Liu, X., Holstege, H., van der Gulden, H., Treur-Mulder, M., Zevenhoven, J., Velds, A., Kerkhoven, R. M., van Vliet, M. H., Wessels, L. F. A., Peterse, J. L., Berns, A., Jonkers, J. (2007). Somatic loss of BRCA1 and p53 in mice induces mammary tumors with features of human BRCA1-mutated basal-like breast cancer. Proc. Natl. Acad. Sci. USA 104: 12111-12116 [Abstract] [Full Text]  
• Tischkowitz, M., Xia, B., Sabbaghian, N., Reis-Filho, J. S., Hamel, N., Li, G., van Beers, E. H., Li, L., Khalil, T., Quenneville, L. A., Omeroglu, A., Poll, A., Lepage, P., Wong, N., Nederlof, P. M., Ashworth, A., Tonin, P. N., Narod, S. A., Livingston, D. M., Foulkes, W. D. (2007). Analysis of PALB2/FANCN-associated breast cancer families. Proc. Natl. Acad. Sci. USA 104: 6788-6793 [Abstract] [Full Text]  
• Behbakht, K., Qamar, L., Aldridge, C. S., Coletta, R. D., Davidson, S. A., Thorburn, A., Ford, H. L. (2007). Six1 Overexpression in Ovarian Carcinoma Causes Resistance to TRAIL-Mediated Apoptosis and Is Associated with Poor Survival. Cancer Res. 67: 3036-3042 [Abstract] [Full Text]  
• Kell, M. R, Burke, J. P (2007). Management of breast cancer in women with BRCA gene mutation. BMJ 334: 437-438 [Full Text]  
• Karppinen, S-M, Barkardottir, R B, Backenhorn, K, Sydenham, T, Syrjakoski, K, Schleutker, J, Ikonen, T, Pylkas, K, Rapakko, K, Erkko, H, Johannesdottir, G, Gerdes, A-M, Thomassen, M, Agnarsson, B A, Grip, M, Kallioniemi, A, Kere, J, Aaltonen, L A, Arason, A, Moller, P, Kruse, T A, Borg, A, Winqvist, R (2006). Nordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignancies. J. Med. Genet. 43: 856-862 [Abstract] [Full Text]  
• Seo, D., Ginsburg, G. S., Goldschmidt-Clermont, P. J. (2006). Gene Expression Analysis of Cardiovascular Diseases: Novel Insights Into Biology and Clinical Applications. J Am Coll Cardiol 48: 227-235 [Abstract] [Full Text]  
• Saeki, H., Siaud, N., Christ, N., Wiegant, W. W., van Buul, P. P. W., Han, M., Zdzienicka, M. Z., Stark, J. M., Jasin, M. (2006). Suppression of the DNA repair defects of BRCA2-deficient cells with heterologous protein fusions. Proc. Natl. Acad. Sci. USA 103: 8768-8773 [Abstract] [Full Text]  
• Zhang, L., Huang, J., Yang, N., Liang, S., Barchetti, A., Giannakakis, A., Cadungog, M. G., O'Brien-Jenkins, A., Massobrio, M., Roby, K. F., Katsaros, D., Gimotty, P., Butzow, R., Weber, B. L., Coukos, G. (2006). Integrative Genomic Analysis of Protein Kinase C (PKC) Family Identifies PKC{iota} as a Biomarker and Potential Oncogene in Ovarian Carcinoma.. Cancer Res. 66: 4627-4635 [Abstract] [Full Text]  
• Ashworth, A. (2006). Defective Double-Strand DNA Repair and Cancer Susceptibility in BRCA Mutation Carriers. aacredbook 2006: 303-306 [Full Text]  
• Wilkening, S., Bermejo, J. L., Burwinkel, B., Klaes, R., Bartram, C. R., Meindl, A., Bugert, P., Schmutzler, R. K., Wappenschmidt, B., Untch, M., Hemminki, K., Forsti, A. (2006). The Single Nucleotide Polymorphism IVS1+309 in Mouse Double Minute 2 Does Not Affect Risk of Familial Breast Cancer. Cancer Res. 66: 646-648 [Abstract] [Full Text]  
• Samuelson, D. J., Aperavich, B. A., Haag, J. D., Gould, M. N. (2005). Fine Mapping Reveals Multiple Loci and a Possible Epistatic Interaction within the Mammary Carcinoma Susceptibility Quantitative Trait Locus, Mcs5. Cancer Res. 65: 9637-9642 [Abstract] [Full Text]  
• Agata, S, Dalla Palma, M, Callegaro, M, Scaini, M C, Menin, C, Ghiotto, C, Nicoletto, O, Zavagno, G, Chieco-Bianchi, L, D'Andrea, E, Montagna, M (2005). Large genomic deletions inactivate the BRCA2 gene in breast cancer families. J. Med. Genet. 42: e64-e64 [Abstract] [Full Text]  
• Ferguson, D. A., Muenster, M. R., Zang, Q., Spencer, J. A., Schageman, J. J., Lian, Y., Garner, H. R., Gaynor, R. B., Huff, J. W., Pertsemlidis, A., Ashfaq, R., Schorge, J., Becerra, C., Williams, N. S., Graff, J. M. (2005). Selective Identification of Secreted and Transmembrane Breast Cancer Markers using Escherichia coli Ampicillin Secretion Trap. Cancer Res. 65: 8209-8217 [Abstract] [Full Text]  
• Nelson, H. D., Huffman, L. H., Fu, R., Harris, E. L. (2005). Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Systematic Evidence Review for the U.S. Preventive Services Task Force. ANN INTERN MED 143: 362-379 [Abstract] [Full Text]  
• Rau, K-M, Kang, H-Y, Cha, T-L, Miller, S A, Hung, M-C (2005). The mechanisms and managements of hormone-therapy resistance in breast and prostate cancers. Endocr Relat Cancer 12: 511-532 [Abstract] [Full Text]  
• Kim, M. Y., Zhang, T., Kraus, W. L. (2005). Poly(ADP-ribosyl)ation by PARP-1: `PAR-laying' NAD+ into a nuclear signal. Genes Dev. 19: 1951-1967 [Abstract] [Full Text]  
• Turner, S. S. (2005). Critical Junctures in Genetic Medicine: The Transformation of DNA Lab Science to Commercial Pharmacogenomics. Journal of Business and Technical Communication 19: 328-352 [Abstract]  
• Choudhury, A. D., Xu, H., Modi, A. P., Zhang, W., Ludwig, T., Baer, R. (2005). Hyperphosphorylation of the BARD1 Tumor Suppressor in Mitotic Cells. J. Biol. Chem. 280: 24669-24679 [Abstract] [Full Text]  
• Thompson, M. E., Robinson-Benion, C. L., Holt, J. T. (2005). An Amino-terminal Motif Functions as a Second Nuclear Export Sequence in BRCA1. J. Biol. Chem. 280: 21854-21857 [Abstract] [Full Text]  
• Brown, P. H., Rashid, A. (2005). Cancer Prevention: The Importance of Accurate Risk Assessment. Cancer Epidemiol. Biomarkers Prev. 14: 1357-1358 [Full Text]  
• Ishimori, T., Patel, P. V., Wahl, R. L. (2005). Detection of Unexpected Additional Primary Malignancies with PET/CT. JNM 46: 752-757 [Abstract] [Full Text]  
• Woodward, A M, Davis, T A, Silva, A G S, kConFab Investigators, , Kirk, J A, Leary, J A (2005). Large genomic rearrangements of both BRCA2 and BRCA1 are a feature of the inherited breast/ovarian cancer phenotype in selected families. J. Med. Genet. 42: e31-e31 [Abstract] [Full Text]  
• Shaag, A., Walsh, T., Renbaum, P., Kirchhoff, T., Nafa, K., Shiovitz, S., Mandell, J. B., Welcsh, P., Lee, M. K., Ellis, N., Offit, K., Levy-Lahad, E., King, M.-C. (2005). Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population. Hum Mol Genet 14: 555-563 [Abstract] [Full Text]  
• Zhang, L., Yang, N., Huang, J., Buckanovich, R. J., Liang, S., Barchetti, A., Vezzani, C., O'Brien-Jenkins, A., Wang, J., Ward, M. R., Courreges, M. C., Fracchioli, S., Medina, A., Katsaros, D., Weber, B. L., Coukos, G. (2005). Transcriptional Coactivator Drosophila Eyes Absent Homologue 2 Is Up-Regulated in Epithelial Ovarian Cancer and Promotes Tumor Growth. Cancer Res. 65: 925-932 [Abstract] [Full Text]  
• Wu, K., Hinson, S. R., Ohashi, A., Farrugia, D., Wendt, P., Tavtigian, S. V., Deffenbaugh, A., Goldgar, D., Couch, F. J. (2005). Functional Evaluation and Cancer Risk Assessment of BRCA2 Unclassified Variants. Cancer Res. 65: 417-426 [Abstract] [Full Text]  
• Powell, C. B., Kenley, E., Chen, L.-m., Crawford, B., McLennan, J., Zaloudek, C., Komaromy, M., Beattie, M., Ziegler, J. (2005). Risk-Reducing Salpingo-Oophorectomy in BRCA Mutation Carriers: Role of Serial Sectioning in the Detection of Occult Malignancy. JCO 23: 127-132 [Abstract] [Full Text]  
• TUTT, A.N.J., LORD, C.J., MCCABE, N., FARMER, H., TURNER, N., MARTIN, N.M., JACKSON, S.P., SMITH, G.C.M., ASHWORTH, A. (2005). Exploiting the DNA Repair Defect in BRCA Mutant Cells in the Design of New Therapeutic Strategies for Cancer. Cold Spring Harb Symp Quant Biol 70: 139-148 [Abstract]  
• Butch, A. W., Chun, H. H., Nahas, S. A., Gatti, R. A. (2004). Immunoassay to Measure Ataxia-Telangiectasia Mutated Protein in Cellular Lysates. Clin. Chem. 50: 2302-2308 [Abstract] [Full Text]  
• Sifri, R., Gangadharappa, S., Acheson, L. S. (2004). Identifying and Testing for Hereditary Susceptibility to Common Cancers. CA Cancer J Clin 54: 309-326 [Abstract] [Full Text]  
• Oh, H. S., Moharita, A., Potian, J. G., Whitehead, I. P., Livingston, J. C., Castro, T. A., Patel, P. S., Rameshwar, P. (2004). Bone Marrow Stroma Influences Transforming Growth Factor-{beta} Production in Breast Cancer Cells to Regulate c-myc Activation of the Preprotachykinin-I Gene in Breast Cancer Cells. Cancer Res. 64: 6327-6336 [Abstract] [Full Text]  
• Karppinen, S-M, Heikkinen, K, Rapakko, K, Winqvist, R (2004). Mutation screening of the BARD1 gene: evidence for involvement of the Cys557Ser allele in hereditary susceptibility to breast cancer. J. Med. Genet. 41: e114-e114 [Full Text]  
• Choudhury, A. D., Xu, H., Baer, R. (2004). Ubiquitination and Proteasomal Degradation of the BRCA1 Tumor Suppressor Is Regulated during Cell Cycle Progression. J. Biol. Chem. 279: 33909-33918 [Abstract] [Full Text]  
• Akahira, J.-i., Sugihashi, Y., Suzuki, T., Ito, K., Niikura, H., Moriya, T., Nitta, M., Okamura, H., Inoue, S., Sasano, H., Okamura, K., Yaegashi, N. (2004). Decreased Expression of 14-3-3{sigma} Is Associated with Advanced Disease in Human Epithelial Ovarian Cancer: Its Correlation with Aberrant DNA Methylation. Clin. Cancer Res. 10: 2687-2693 [Abstract] [Full Text]  
• Tan, W., Zheng, L., Lee, W.-H., Boyer, T. G. (2004). Functional Dissection of Transcription Factor ZBRK1 Reveals Zinc Fingers with Dual Roles in DNA-binding and BRCA1-dependent Transcriptional Repression. J. Biol. Chem. 279: 6576-6587 [Abstract] [Full Text]  
• Esteban-Cardenosa, E., Duran, M., Infante, M., Velasco, E., Miner, C. (2004). High-Throughput Mutation Detection Method to Scan BRCA1 and BRCA2 Based on Heteroduplex Analysis by Capillary Array Electrophoresis. Clin. Chem. 50: 313-320 [Abstract] [Full Text]  
• Simonds, W. F., Robbins, C. M., Agarwal, S. K., Hendy, G. N., Carpten, J. D., Marx, S. J. (2004). Familial Isolated Hyperparathyroidism Is Rarely Caused by Germline Mutation in HRPT2, the Gene for the Hyperparathyroidism-Jaw Tumor Syndrome. J. Clin. Endocrinol. Metab. 89: 96-102 [Abstract] [Full Text]  
• Brandt, B., Hermann, S., Straif, K., Tidow, N., Buerger, H., Chang-Claude, J. (2004). Modification of Breast Cancer Risk in Young Women by a Polymorphic Sequence in the egfr Gene. Cancer Res. 64: 7-12 [Abstract] [Full Text]  
• Macgregor, J. T. (2004). Biomarkers of Cancer Risk and Therapeutic Benefit: New Technologies, New Opportunities, and Some Challenges. Toxicol Pathol 32: 99-105 [Abstract]  
• Guttmacher, A. E., Collins, F. S. (2003). Welcome to the Genomic Era. NEJM 349: 996-998 [Full Text]  
• Friedenson, B., Piver, M. S., Weber, B. L., Wooster, R. (2003). Breast-Cancer Genomics. NEJM 349: 910-911 [Full Text]