Limits...
Triple-negative, basal-like, and quintuple-negative breast cancers: better prediction model for survival.

Choi YL, Oh E, Park S, Kim Y, Park YH, Song K, Cho EY, Hong YC, Choi JS, Lee JE, Kim JH, Nam SJ, Im YH, Yang JH, Shin YK - BMC Cancer (2010)

Bottom Line: The results of this study showed that both TNBCs and BLBCs were associated with high histological and/or nuclear grades.After multivariate analysis of TNBCs, the BLBCs did not have a worse prognosis than the QNBC/5NPs.Interestingly, the patients with BLBCs showed significant adjuvant chemotherapy benefit.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Seoul, Korea.

ABSTRACT

Background: Triple-negative breast cancers (TNBCs) and basal-like breast cancers (BLBCs) are known as poor outcome subtypes with a lack of targeted therapy. Previous studies have shown conflicting results regarding the difference of prognostic significance between TNBCs and BLBCs. In this study, we aimed to characterize the prognostic features of TNBCs, in view of BLBCs and quintuple-negative breast cancers (QNBC/5NPs).

Methods: Using tissue microarray-based immunohistochemical analysis, we categorized 951 primary breast cancers into four or five subtypes according to the expression of ER, PR, HER2, and basal markers (CK5/6, EGFR).

Results: The results of this study showed that both TNBCs and BLBCs were associated with high histological and/or nuclear grades. When the TNBCs are divided into two subtypes by the presence of basal markers, the clinicopathologic characteristics of TNBCs were mainly maintained in the BLBCs. The 5-subgrouping was the better prediction model for both disease free and overall survival in breast cancers than the 4-subgrouping. After multivariate analysis of TNBCs, the BLBCs did not have a worse prognosis than the QNBC/5NPs. Interestingly, the patients with BLBCs showed significant adjuvant chemotherapy benefit. In addition, QNBC/5NPs comprised about 6~8% of breast cancers in publicly available breast cancer datasets

Conclusion: The QNBC/5NP subtype is a worse prognostic subgroup of TNBCs, especially in higher stage and this result may be related to adjuvant chemotherapy benefit of BLBCs, calling for caution in the identification of subgroups of patients for therapeutic classification.

Show MeSH

Related in: MedlinePlus

Comparison of the expression levels of five genes according to five subtypes in the microarray data sets. (A) Proportion of five breast cancer subtypes in two large-sized microarray data sets. (B) Expression levels of the five markers according to the subtypes in Vijver et al. (C) Expression levels of the five markers according to the subtypes in Wang et al. Distribution of expression levels of each marker was described with box plots. The bottom and top of the box are the 25th and 75th percentile, and the band near the middle of the box is the 50th percentile.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2957395&req=5

Figure 4: Comparison of the expression levels of five genes according to five subtypes in the microarray data sets. (A) Proportion of five breast cancer subtypes in two large-sized microarray data sets. (B) Expression levels of the five markers according to the subtypes in Vijver et al. (C) Expression levels of the five markers according to the subtypes in Wang et al. Distribution of expression levels of each marker was described with box plots. The bottom and top of the box are the 25th and 75th percentile, and the band near the middle of the box is the 50th percentile.

Mentions: In order to support our data that TNBC is substantially different from BLBC, we explored the mRNA expression levels of the five genes (ESR1, PGR, ERBB2, KRT5 and EGFR) according to five subtypes in two large-sized microarray datasets. We classified each dataset into five subtypes from the definition of subtypes described in Methods. From the classification, the proportion of five subtypes in the two microarray datasets turned out to be very similar, and it was similar to the proportion of subtypes in Cheang et al.'s data set as well (Fig 4A). The proportion of QNBC/5NP within TNBC was about 36% and 50% in each microarray dataset, and our data set showed similar proportion which was about 40%. The expression patterns of each gene in five subtypes were consistent across the datasets displaying the clear characteristics of each subtype. Elevated expression of KRT5 and EGFR was a distinct feature of BLBC discriminating it from the other subtypes, and their high expression in BLBC were independent from the expression of other three genes - ESR1, PGR and ERBB2 - which showed no difference between BLBC and QNBC/5NP (Figure 4B and 4C). KRT5 showed a wide range of expression level across samples, while the expression range of EGFR was relatively very narrow in both datasets, and most of the TNBC samples showing high expression of KRT5 accompanied high expression of EGFR (data not shown). From the overall expression patterns of five genes, KRT5 and EGFR seemed to be one of the major causes of the heterogeneity of TNBC, and a large portion of TNBC was non-BLBC subtypes supporting that TNBC should not be replaced interchangeably with BLBC.


Triple-negative, basal-like, and quintuple-negative breast cancers: better prediction model for survival.

Choi YL, Oh E, Park S, Kim Y, Park YH, Song K, Cho EY, Hong YC, Choi JS, Lee JE, Kim JH, Nam SJ, Im YH, Yang JH, Shin YK - BMC Cancer (2010)

Comparison of the expression levels of five genes according to five subtypes in the microarray data sets. (A) Proportion of five breast cancer subtypes in two large-sized microarray data sets. (B) Expression levels of the five markers according to the subtypes in Vijver et al. (C) Expression levels of the five markers according to the subtypes in Wang et al. Distribution of expression levels of each marker was described with box plots. The bottom and top of the box are the 25th and 75th percentile, and the band near the middle of the box is the 50th percentile.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2957395&req=5

Figure 4: Comparison of the expression levels of five genes according to five subtypes in the microarray data sets. (A) Proportion of five breast cancer subtypes in two large-sized microarray data sets. (B) Expression levels of the five markers according to the subtypes in Vijver et al. (C) Expression levels of the five markers according to the subtypes in Wang et al. Distribution of expression levels of each marker was described with box plots. The bottom and top of the box are the 25th and 75th percentile, and the band near the middle of the box is the 50th percentile.
Mentions: In order to support our data that TNBC is substantially different from BLBC, we explored the mRNA expression levels of the five genes (ESR1, PGR, ERBB2, KRT5 and EGFR) according to five subtypes in two large-sized microarray datasets. We classified each dataset into five subtypes from the definition of subtypes described in Methods. From the classification, the proportion of five subtypes in the two microarray datasets turned out to be very similar, and it was similar to the proportion of subtypes in Cheang et al.'s data set as well (Fig 4A). The proportion of QNBC/5NP within TNBC was about 36% and 50% in each microarray dataset, and our data set showed similar proportion which was about 40%. The expression patterns of each gene in five subtypes were consistent across the datasets displaying the clear characteristics of each subtype. Elevated expression of KRT5 and EGFR was a distinct feature of BLBC discriminating it from the other subtypes, and their high expression in BLBC were independent from the expression of other three genes - ESR1, PGR and ERBB2 - which showed no difference between BLBC and QNBC/5NP (Figure 4B and 4C). KRT5 showed a wide range of expression level across samples, while the expression range of EGFR was relatively very narrow in both datasets, and most of the TNBC samples showing high expression of KRT5 accompanied high expression of EGFR (data not shown). From the overall expression patterns of five genes, KRT5 and EGFR seemed to be one of the major causes of the heterogeneity of TNBC, and a large portion of TNBC was non-BLBC subtypes supporting that TNBC should not be replaced interchangeably with BLBC.

Bottom Line: The results of this study showed that both TNBCs and BLBCs were associated with high histological and/or nuclear grades.After multivariate analysis of TNBCs, the BLBCs did not have a worse prognosis than the QNBC/5NPs.Interestingly, the patients with BLBCs showed significant adjuvant chemotherapy benefit.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Seoul, Korea.

ABSTRACT

Background: Triple-negative breast cancers (TNBCs) and basal-like breast cancers (BLBCs) are known as poor outcome subtypes with a lack of targeted therapy. Previous studies have shown conflicting results regarding the difference of prognostic significance between TNBCs and BLBCs. In this study, we aimed to characterize the prognostic features of TNBCs, in view of BLBCs and quintuple-negative breast cancers (QNBC/5NPs).

Methods: Using tissue microarray-based immunohistochemical analysis, we categorized 951 primary breast cancers into four or five subtypes according to the expression of ER, PR, HER2, and basal markers (CK5/6, EGFR).

Results: The results of this study showed that both TNBCs and BLBCs were associated with high histological and/or nuclear grades. When the TNBCs are divided into two subtypes by the presence of basal markers, the clinicopathologic characteristics of TNBCs were mainly maintained in the BLBCs. The 5-subgrouping was the better prediction model for both disease free and overall survival in breast cancers than the 4-subgrouping. After multivariate analysis of TNBCs, the BLBCs did not have a worse prognosis than the QNBC/5NPs. Interestingly, the patients with BLBCs showed significant adjuvant chemotherapy benefit. In addition, QNBC/5NPs comprised about 6~8% of breast cancers in publicly available breast cancer datasets

Conclusion: The QNBC/5NP subtype is a worse prognostic subgroup of TNBCs, especially in higher stage and this result may be related to adjuvant chemotherapy benefit of BLBCs, calling for caution in the identification of subgroups of patients for therapeutic classification.

Show MeSH
Related in: MedlinePlus