How basal are triple-negative breast cancers?
The basal molecular subtype of breast cancer (BC) is defined by the mRNA expression pattern of an intrinsic approximately 500-gene set. It is the most homogeneous subtype in transcriptional terms, and one of the most aggressive in prognostic terms. Clinical trials testing new systemic therapeutic strategies have been launched in basal BCs. Although no proof of evidence has yet been reported, basal tumors are currently assimilated to and selected as triple-negative (TN) BCs in these trials because of their frequent immunohistochemical (IHC) negativity for hormone and ERBB2 receptors. Here, we have assessed the degrees of correlation and of homogeneity of the TN phenotype (IHC-based definition) and the basal subtype (gene expression-based definition). We analyzed 172 TN BCs defined by gene expression profile as basal (123 cases) and nonbasal (49 cases). Conversely, 160 tumors were defined as basal by their gene expression profile and included 123 TN and 37 non-TN samples. Uni- and multivariate analyses revealed that TN BCs represent a more heterogeneous group than basal BCs, including basal and nonbasal tumors very different both at the histoclinical and molecular level, notably for mRNA expression of molecules targeted by specific therapies under evaluation in clinical trials. These results call for caution in the interpretation of ongoing trials and selection of patients in future trials. They also warrant the identification of molecular markers for basal BCs more clinically applicable than gene expression profiles.
Bertucci
François
F
Centre de Recherche en Cancérologie de Marseille, Département d'Oncologie Moléculaire, Institut Paoli-Calmettes (IPC) et UMR599 Inserm, Marseille, France. bertuccif@marseille.fnclcc.fr
Finetti
Pascal
P
Cervera
Nathalie
N
Esterni
Benjamin
B
Hermitte
Fabienne
F
Viens
Patrice
P
Birnbaum
Daniel
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry; D018275:Carcinoma, Lobular / Q000737:chemistry; D018276:Carcinoma, Medullary / Q000737:chemistry; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis* / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis* / Q000235:genetics
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone