Triple-negative breast cancer: present challenges and new perspectives.
Triple-negative breast cancers (TNBC), characterized by absence of estrogen receptor (ER), progesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2), are typically associated with poor prognosis, due to aggressive tumor phenotype(s), only partial response to chemotherapy and present lack of clinically established targeted therapies. Advances in the design of individualized strategies for treatment of TNBC patients require further elucidation, by combined 'omics' approaches, of the molecular mechanisms underlying TNBC phenotypic heterogeneity, and the still poorly understood association of TNBC with BRCA1 mutations. An overview is here presented on TNBC profiling in terms of expression signatures, within the functional genomic breast tumor classification, and ongoing efforts toward identification of new therapy targets and bioimaging markers. Due to the complexity of aberrant molecular patterns involved in expression, pathological progression and biological/clinical heterogeneity, the search for novel TNBC biomarkers and therapy targets requires collection of multi-dimensional data sets, use of robust multivariate data analysis techniques and development of innovative systems biology approaches.
Podo
Franca
F
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. franca.podo@iss.it
Buydens
Lutgarde M C
LM
Degani
Hadassa
H
Hilhorst
Riet
R
Klipp
Edda
E
Gribbestad
Ingrid S
IS
Van Huffel
Sabine
S
van Laarhoven
Hanneke W M
HW
Luts
Jan
J
Monleon
Daniel
D
Postma
Geert J
GJ
Schneiderhan-Marra
Nicole
N
Santoro
Filippo
F
Wouters
Hans
H
Russnes
Hege G
HG
Sørlie
Therese
T
Tagliabue
Elda
E
Børresen-Dale
Anne-Lise
AL
D000970:Antineoplastic Agents / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D005260:Female; D006801:Humans; D057285:Precision Medicine; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D049490:Systems Biology / Q000379:methods
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone