Abstract
For more than 10 years, continuous development of new high through-put technologies has given to scientists a wide range of diverse but complementary tools to study biology in general and cancers in particular. These tools can address simultaneous, genome-wide studies of DNA copy number alterations (amplification, gain or losses), loss of heterozygosity (LOH), gene-expression alterations, microRNA post-transcriptional control alterations and protein complex activations. We present here a summary of the discoveries generated by gene-expression studies of breast cancers that stresses their direct implications in the care of patients. Terabytes of biological data, gathered throughout the years by the scientist, are not the by-product of some technological whim but, on the contrary, seminal information for the modern characterisation of these tumours. To improve the prognosis of breast cancer patients requires the use of these technologies.
Résumé
Depuis plus de dix ans, le développement continu de nouvelles technologies d’analyse à haut débit offre aux scientifiques la possibilité d’étudier la biologie du vivant en général et des cancers en particulier par des voies aussi différentes que complémentaires. Ainsi, les altérations de la structure de l’ADN (amplification, délétion, gain), les pertes d’hétérozygotie (LOH), les altérations du niveau d’expression des gènes, les altérations du contrôle posttranscriptionnelle des microARN, l’activation des complexes protéiques peuvent être analysées simultanément à l’échelle du génome humain. Nous présentons ici un résumé des découvertes obtenues par l’analyse à haut débit du profil d’expression des cancers du sein, en insistant particulièrement sur l’impact majeur de ces travaux sur la connaissance et la prise en charge clinique de ces patientes. Les terabytes de données biologiques accumulées par les scientifiques depuis plus de dix ans ne répondent pas simplement à une lubie technologique mais sont au contraire des outils déterminants de la dissection moderne de ces tumeurs. L’amélioration du pronostic des patientes atteintes de cancer du sein passe nécessairement par l’utilisation de ces technologies.
Similar content being viewed by others
Bibliographie
Andre F, Mazouni C, Hortobagyi GN, Pusztai L (2006) DNA arrays as predictors of efficacy of adjuvant/neoadjuvant chemotherapy in breast cancer patients: current data and issues on study design. Biochim Biophys Acta 1766(2): 197–204
Brekelmans CT, Tilanus-Linthorst MM, Seynaeve C, et al. (2007) Tumor characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases. Eur J Cancer 43(5): 867–876
Carey LA, Dees EC, Sawyer L, et al. (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13(8): 2329–2334
Clarke M, Collins R, Darby S, et al. (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366(9503): 2087–2106
Crabb SJ, Cheang MC, Leung S, et al. (2008) Basal breast cancer molecular subtype predicts for lower incidence of axillary lymph node metastases in primary breast cancer. Clin Breast Cancer 8 (3): 249–256
Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19(5): 403–410
Gowen LC, Avrutskaya AV, Latour AM, et al. (1998) BRCA1 required for transcription-coupled repair of oxidative DNA damage. Science 281(5379): 1009–1012
Haffty BG, Yang Q, Reiss M, et al. (2006) Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol 24(36): 5652–5657
Hijal (2010) Locoregional recurrences in triple-negative, node-negative early stage breast cancer treated with breast-conserving treatment. EBCC 2010
Horton JK, Halle J, Ferraro M, et al. (2010) Radiosensitization of chemotherapy-refractory, locally advanced or locally recurrent breast cancer with trastuzumab: a phase II trial. Int J Radiat Oncol Biol Phys 76(4): 998–1004
Hu Z, Fan C, Oh DS, et al. (2006) The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 7: 96
Kim MJ, Ro JY, Ahn SH, et al. (2006) Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol 37(9): 1217–1226
Kirova YM, Savignoni A, Sigal-Zafrani B, et al. (2010) Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Longterm results and review of the literature. Breast Cancer Res Treat 120(1): 119–126
Kyndi M, Overgaard M, Nielsen HM, et al. (2009) High local recurrence risk is not associated with large survival reduction after postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of DBCG 82 b&c. Radiother Oncol 90(1): 74–79
Lander ES, Linton LM, Birren B, et al. (2001) Initial sequencing and analysis of the human genome. Nature 409(6822): 860–921
Liang K, Lu Y, Jin W, et al. (2003) Sensitization of breast cancer cells to radiation by trastuzumab. Mol Cancer Ther 2(11): 1113–1120
Linn SC, Van’t Veer LJ (2009) Clinical relevance of the triple negative breast cancer concept: genetic basis and clinical utility of the concept. Eur J Cancer 45(Suppl 1): 11–26
Liu H, Fan Q, Zhang Z, et al. (2008) Basal-HER2 phenotype shows poorer survival than basal-like phenotype in hormone receptor-negative invasive breast cancers. Hum Pathol 39(2): 167–174
Loi S, Haibe-Kains B, Desmedt C, et al. (2007) Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. J Clin Oncol 25(10): 1239–1246
Lu X, Wang ZC, Iglehart JD, et al. (2008) Predicting features of breast cancer with gene expression patterns. Breast Cancer Res Treat 108(2): 191–201
Millar EK, Graham PH, O’Toole SA, et al. (2009) Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage invasive breast cancer using a five-biomarker panel. J Clin Oncol 27(28): 4701–4708
Nguyen PL, Taghian AG, Katz MS, et al. (2008) Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol 26(14): 2373–2378
O’shaughnessy (2009) SABCS, Abs 207 2009
O’shaughnessy JOC, Pippen J (2009) Efficacy of BSI-201, a poly (ADP-ribose) polymerase 1 (PARP-1) inhibitor, in combination with gemcitabine-carboplatin (G-C) in patients with metastatic triple negative breast cancer (TNBC): results of a randomized phase II trial. J Clin Oncol 27(Suppl): 793s
Parikh RR, Housman D, Yang Q, et al. (2008) Prognostic value of triple negative phenotype at the time of locally recurrent, conservatively treated breast cancer. Int J Radiat Oncol Biol Phys 72(4): 1056–63
Perou CM, Sorlie T, Eisen MB, et al. (2000) Molecular portraits of human breast tumors. Nature 406(6797): 747–752
Pierce LJ, Levin AM, Rebbeck TR, et al. (2006) Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol 24(16): 2437–2443
Pietras RJ, Poen JC, Gallardo D, et al. (1999) Monoclonal antibody to HER-2/neureceptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res 59(6): 1347–1355
Ravdin PM (1995) A computer based program to assist in adjuvant therapy decisions for individual breast cancer patients. Bull Cancer 82(Suppl 5): 561s–564s
Rouzier R, Perou CM, Symmans WF, et al. (2005) Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11(16): 5678–5685
Sartor CI (2003) Radiosensitization of locally advanced breast cancer with HER-CEPTIN-initial toxicity results of a phase II trial. 26th Annual San Antonio Breast Cancer Symposium, San Antonio, USA
Schena M, Heller RA, Theriault TP, et al. (1998) Microarrays: biotechnology’s discovery platform for functional genomics. Trends Biotechnol 16(7): 301–306
Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270(5235): 467–470
Smid M, Wang Y, Zhang Y, et al. (2008) Subtypes of breast cancer show preferential site of relapse. Cancer Res 68(9): 3108–3114
Sorlie T, Perou CM, Tibshirani R, et al. (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19): 10869–10874
Sotiriou C, Wirapati P, Loi S, et al. (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98(4): 262–272
Tutt ARM, Garber JE (2009) Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breastcancer. J Clin Oncol 27(803s): abstr CRA501
Venter JC, Adams MD, Myers EW, et al. (2001) The sequence of the human genome. Science 291(5507): 1304–1351
Vrieling C, Collette L, Fourquet A, et al. (2003) Can patient, treatment and pathology related characteristics explain the high local recurrence rate following breast-conserving therapy in young patients? Eur J Cancer 39(7): 932–44
Wirapati P, Sotiriou C, Kunkel S, et al. (2008) Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures. Breast Cancer Res 10(4): R65
Author information
Authors and Affiliations
About this article
Cite this article
Reyal, F., Bollet, M.A., Roubaud, G. et al. Les sous-types moléculaires du cancer du sein. Apport des technologies à haut débit. Oncologie 12, 396–402 (2010). https://doi.org/10.1007/s10269-010-1907-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10269-010-1907-6