
INTEGRATED GENOMIC ANALYSIS OF BREAST CANCERS Addou-Klouche L1,2, Adélaïde1 J, Cornen S1, Bekhouche I1, Finetti P1, Guille A1,
Sircoulomb F1, Raynaud S1, Bertucci F1,3,4, Birnbaum D1, Chaffanet M1,* *Corresponding Author: Max Chaffanet, Ph.D., HDR, Department of Molecular Oncology, Institut Paoli
Calmettes, 232 Boulevard Sainte Marguerite, 13009 Marseille, France; Tel.: +33-(0)4-91-22-34-77; Fax: +33-
(0)4-91-22-35-44; E-mail: CHAFFANETM@ipc.unicancer.fr page: 71 download article in pdf format
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Abstract
Breast cancer is the most frequent and the most
deadly cancer in women in Western countries.
Different classifications of disease (anatomoclinical,
pathological, prognostic, genetic) are used for
guiding the management of patients. Unfortunately,
they fail to reflect the whole clinical heterogeneity
of the disease. Consequently, molecularly distinct
diseases are grouped in similar clinical classes,
likely explaining the different clinical outcome
between patients in a given class, and the fact that
selection of the most appropriate diagnostic or
therapeutic strategy for each patient is not done accurately.
Today, treatment is efficient in only 70.0-
75.0% of cases overall. Our repertoire of efficient
drugs is limited but is being expanded with the
discovery of new molecular targets for new drugs,
based on the identification of candidate oncogenes
and tumor suppressor genes (TSG) functionally relevant
in disease. Development of new drugs makes therapeutical decisions even more demanding of
reliable classifiers and prognostic/predictive tests.
Breast cancer is a complex, heterogeneous disease
at the molecular level. The combinatorial molecular
origin and the heterogeneity of malignant cells, and
the variability of the host background, create distinct
subgroups of tumors endowed with different
phenotypic features such as response to therapy and
clinical outcome. Cellular and molecular analyses
can identify new classes biologically and clinically
relevant, as well as provide new clinically relevant
markers and targets.
The various stages of mammary tumorigenesis
are not clearly defined and the genetic and epigenetic
events critical to the development and aggressiveness
of breast cancer are not precisely known.
Because the phenotype of tumors is dependent on
many genes, a large-scale and integrated molecular
characterization of the genetic and epigenetic alterations
and gene expression deregulation should allow
the identification of new molecular classes clinically
relevant, as well as among the altered genes
and/or pathways, the identification of more accurate
molecular diagnostic, prognostic/predictive factors,
and for some of them, after functional validation,
the identification of new therapeutic targets.
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