Limits...
Identification of a novel luminal molecular subtype of breast cancer.

Dvorkin-Gheva A, Hassell JA - PLoS ONE (2014)

Bottom Line: All of the unclassifiable samples could be grouped into a new molecular subtype, which we termed "luminal-like".We found that patients harboring tumors of the luminal-like subtype have a better prognosis than those with basal-like breast cancer, a similar prognosis to those with ERBB2+, luminal B or claudin-low tumors, but a worse prognosis than patients with luminal A or normal-like breast tumors.Our findings suggest the occurrence of another molecular subtype of breast cancer that accounts for the vast majority of previously unclassifiable breast tumors.

View Article: PubMed Central - PubMed

Affiliation: Centre for Functional Genomics, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT
The molecular classification of human breast tumors has afforded insights into subtype specific biological processes, patient prognosis and response to therapies. However, using current methods roughly one quarter of breast tumors cannot be classified into one or another molecular subtype. To explore the possibility that the unclassifiable samples might comprise one or more novel subtypes we employed a collection of publically available breast tumor datasets with accompanying clinical information to assemble 1,593 transcript profiles: 25% of these samples could not be assigned to one of the current molecular subtypes of breast cancer. All of the unclassifiable samples could be grouped into a new molecular subtype, which we termed "luminal-like". We also identified the luminal-like subtype in an independent collection of tumor samples (NKI295). We found that patients harboring tumors of the luminal-like subtype have a better prognosis than those with basal-like breast cancer, a similar prognosis to those with ERBB2+, luminal B or claudin-low tumors, but a worse prognosis than patients with luminal A or normal-like breast tumors. Our findings suggest the occurrence of another molecular subtype of breast cancer that accounts for the vast majority of previously unclassifiable breast tumors.

Show MeSH

Related in: MedlinePlus

Correlation of 397 unclassified samples with 7 subtypes.A. Distribution of samples based on highest correlation coefficient (excluding the correlation to “Luminal-like” centroid) B. Comparison of the same correlation coefficients across subtypes. The basal-like subtype showed lower coefficients than the luminal A and luminal B subtypes and claudin-low subtype showed lower coefficients than luminal B subtype (Kruskal-Wallis (p-value = 0.0004, post-hoc Dunn’s multiple comparison test)).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4116208&req=5

pone-0103514-g002: Correlation of 397 unclassified samples with 7 subtypes.A. Distribution of samples based on highest correlation coefficient (excluding the correlation to “Luminal-like” centroid) B. Comparison of the same correlation coefficients across subtypes. The basal-like subtype showed lower coefficients than the luminal A and luminal B subtypes and claudin-low subtype showed lower coefficients than luminal B subtype (Kruskal-Wallis (p-value = 0.0004, post-hoc Dunn’s multiple comparison test)).

Mentions: We wondered whether the luminal-like subtype was an artifact, resulting from the fact that the luminal A and luminal B standardized centroids do not reflect the variability of all samples that comprise these two subtypes. Hence we tested whether the 397 samples could be classified as either luminal A or luminal B if a correlation coefficient of less than 0.3 was used. As shown in Figure 2A in the absence of a luminal-like centroid, only 53% of samples would have been assigned to either the luminal A or luminal B subtypes, if correlation coefficients cutoff of less than 0.3 was used (for full list of samples and their assigned subtypes, see Table S4). The latter finding indicates that the gene expression profiles of nearly half of the unclassifiable samples had a lower correlation to the luminal A and B subtypes, than they did to the other subtypes, and therefore could not be assigned to either the luminal A or B subtypes, yet possessed luminal characteristics.


Identification of a novel luminal molecular subtype of breast cancer.

Dvorkin-Gheva A, Hassell JA - PLoS ONE (2014)

Correlation of 397 unclassified samples with 7 subtypes.A. Distribution of samples based on highest correlation coefficient (excluding the correlation to “Luminal-like” centroid) B. Comparison of the same correlation coefficients across subtypes. The basal-like subtype showed lower coefficients than the luminal A and luminal B subtypes and claudin-low subtype showed lower coefficients than luminal B subtype (Kruskal-Wallis (p-value = 0.0004, post-hoc Dunn’s multiple comparison test)).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4116208&req=5

pone-0103514-g002: Correlation of 397 unclassified samples with 7 subtypes.A. Distribution of samples based on highest correlation coefficient (excluding the correlation to “Luminal-like” centroid) B. Comparison of the same correlation coefficients across subtypes. The basal-like subtype showed lower coefficients than the luminal A and luminal B subtypes and claudin-low subtype showed lower coefficients than luminal B subtype (Kruskal-Wallis (p-value = 0.0004, post-hoc Dunn’s multiple comparison test)).
Mentions: We wondered whether the luminal-like subtype was an artifact, resulting from the fact that the luminal A and luminal B standardized centroids do not reflect the variability of all samples that comprise these two subtypes. Hence we tested whether the 397 samples could be classified as either luminal A or luminal B if a correlation coefficient of less than 0.3 was used. As shown in Figure 2A in the absence of a luminal-like centroid, only 53% of samples would have been assigned to either the luminal A or luminal B subtypes, if correlation coefficients cutoff of less than 0.3 was used (for full list of samples and their assigned subtypes, see Table S4). The latter finding indicates that the gene expression profiles of nearly half of the unclassifiable samples had a lower correlation to the luminal A and B subtypes, than they did to the other subtypes, and therefore could not be assigned to either the luminal A or B subtypes, yet possessed luminal characteristics.

Bottom Line: All of the unclassifiable samples could be grouped into a new molecular subtype, which we termed "luminal-like".We found that patients harboring tumors of the luminal-like subtype have a better prognosis than those with basal-like breast cancer, a similar prognosis to those with ERBB2+, luminal B or claudin-low tumors, but a worse prognosis than patients with luminal A or normal-like breast tumors.Our findings suggest the occurrence of another molecular subtype of breast cancer that accounts for the vast majority of previously unclassifiable breast tumors.

View Article: PubMed Central - PubMed

Affiliation: Centre for Functional Genomics, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT
The molecular classification of human breast tumors has afforded insights into subtype specific biological processes, patient prognosis and response to therapies. However, using current methods roughly one quarter of breast tumors cannot be classified into one or another molecular subtype. To explore the possibility that the unclassifiable samples might comprise one or more novel subtypes we employed a collection of publically available breast tumor datasets with accompanying clinical information to assemble 1,593 transcript profiles: 25% of these samples could not be assigned to one of the current molecular subtypes of breast cancer. All of the unclassifiable samples could be grouped into a new molecular subtype, which we termed "luminal-like". We also identified the luminal-like subtype in an independent collection of tumor samples (NKI295). We found that patients harboring tumors of the luminal-like subtype have a better prognosis than those with basal-like breast cancer, a similar prognosis to those with ERBB2+, luminal B or claudin-low tumors, but a worse prognosis than patients with luminal A or normal-like breast tumors. Our findings suggest the occurrence of another molecular subtype of breast cancer that accounts for the vast majority of previously unclassifiable breast tumors.

Show MeSH
Related in: MedlinePlus