Biomarkers for Basal-like Breast Cancer

Choo, Jennifer; Nielsen, Torsten O.

doi:10.3390/cancers2021040

Cited by 42 publications

(35 citation statements)

References 170 publications

(235 reference statements)

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“…There are several reported biomarkers associated with BLBC as well as putative candidates suitable for immunohistochemical screening (Table 1) [10,11,23], however, currently, there is no specific international consensus on complement biomarkers that can define BLBC.…”

Section: Molecular Profile Of Blbcmentioning

confidence: 99%

Molecular insights on basal-like breast cancer

Dominguez‐Valentin

Silva

Privat

et al. 2012

Breast Cancer Res Treat

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Molecular classification of breast cancer (BC) identified diverse subgroups that encompass distinct biological behaviour and clinical implications, in particular in relation to prognosis, spread, and incidence of recurrence. Basal like breast cancers (BLBC) compose up to 15% of BC and are characterized by lack of estrogen receptor (ER), progesterone receptor (PR), and HER-2 amplification with expression of basal cytokeratins 5/6, 14, 17, epidermal growth factor receptor (EGFR), and/or c-KIT. There is an overlap in definition between triple-negative BC and BLBC due to the triple-negative profile of BLBC. Also, most BRCA1-associated BCs are BLBC, triple negative, and express basal cytokeratins (5/6, 14, 17) and EGFR.There is a link between sporadic BLBC (occurring in women without germline BRCA1 mutations) with dysfunction of the BRCA1 pathway. Despite the molecular and clinical similarities, these subtypes respond differently to neoadjuvant therapy. BLBCs are associated with an aggressive phenotype, high histological grade, poor clinical behavior, and high rates of recurrences and/or metastasis. Their molecular features render these tumors especially refractory to anti-hormonal-based therapies and the overall prognosis of this subset remains poor. In this article the molecular profile, genomic and epigenetic characteristics as well as BRCA1 pathway dysfunction, clinicopathological behavior, and therapeutic options in BLBC are presented, with emphasis on the discordant findings in current literature.

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Section: Molecular Profile Of Blbcmentioning

confidence: 99%

Molecular insights on basal-like breast cancer

Dominguez‐Valentin

Silva

Privat

et al. 2012

Breast Cancer Res Treat

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“…However, the immunohistochemical distribution of tumors using basal markers can be fairly unreliable. So, data from other research show a significant variation in the presence of basal-like tumors among the analyzed triple negative breast cancers, ranging from 42% to 88% 9,[15][16][17] . However, our data on the distribution of each tumor subtype are in accordance with the data available, even those in which the classification was based on the expression of 500 different genes and where the presence of basal-like tumor was 71% 9 .…”

Section: Discussionmentioning

confidence: 77%

Immunohistochemical Differentiation of Triple Negative Breast Cancer

Lesar

Stanec

Lesar³

et al. 2016

ACC

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SUMMARY -Based on immunohistochemical staining for the basal markers cytokeratin 5/6 (CK 5/6), cytokeratin 14 (CK 14) and P-cadherin, triple negative tumors (TNT) are divided into two groups: 1) basal-like (BL) positive for one or all three markers; and 2) non basal-like (NBL) negative for all three markers. Even though the different origin of the cells of these two types of tumors implies different biological properties, they had been treated as one entity until recently. This paper analyzes TNT collected from 150 patients and distributed into two groups according to the results of immunohistochemical analysis, i.e. BL 116 (77.3%) and NBL 34 (22.67%). In this study, CK 5/6, CK 14 and P-cadherin were used as markers for identifying BL tumors. The immunohistochemical reaction was positive for CK 5/6 in 37%, for CK 14 in 50.86% and for P-cadherin in 68.34% of cases. The subclassification of triple negative breast cancer using the basal markers CK 5/6, CK 14 and P-cadherin has enabled identification of BL and NBL breast cancers in a proportion that is in line with the only accurate analysis of TNT gene expression. Using the mentioned combination of markers in daily practice is easy to perform and economically affordable.

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“…Surrogate immunohistochemical definitions for basal-like breast cancer, despite moderate sensitivity and specificity, have been more frequently employed by both the research and medical communities. Building on the clinical ER/ PR/HER2 TNP, basal cytokeratin definitions and the combined immunopanel described in our previous work, 14,16 a large and evolving body of research has since described additional biomarkers for basal-like breast cancer (reviewed in Choo et al 31 ).…”

Section: Discussionmentioning

confidence: 99%

“…14,30 The past few years have seen a plethora of biomarkers described as having an association with the basal-like or triple-negative phenotypes. 31,32 Only some have been validated on independent series, very few have been compared with a gene expression gold standard, and no study has compared large numbers of these candidate biomarkers in parallel in a single validation series. In line with current pathology practices that rely on immunohistochemistry and concurrent morphological examination, we sought to evaluate 72 proposed basal-like biomarkers, drawn from recent gene expression profile data and published literature, on sections from the same breast cancer tissue microarray in which intrinsic subtype has been assigned by a PAM50 gene expression profile assay.…”

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confidence: 99%

A survey of immunohistochemical biomarkers for basal-like breast cancer against a gene expression profile gold standard

et al. 2013

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Gene expression profiling of breast cancer delineates a particularly aggressive subtype referred to as 'basallike', which comprises B15% of all breast cancers, afflicts younger women and is refractory to endocrine and anti-HER2 therapies. Immunohistochemical surrogate definitions for basal-like breast cancer, such as the clinical ER/PR/HER2 triple-negative phenotype and models incorporating positive expression for CK5 (CK5/6) and/or EGFR are heavily cited. However, many additional biomarkers for basal-like breast cancer have been described in the literature. A parallel comparison of 46 proposed immunohistochemical biomarkers of basal-like breast cancer was performed against a gene expression profile gold standard on a tissue microarray containing 42 basal-like and 80 non-basal-like breast cancer cases. Ki67 and PPH3 were the most sensitive biomarkers (both 92%) positively expressed in the basal-like subtype, whereas CK14, IMP3 and NGFR were the most specific (100%). Among biomarkers surveyed, loss of INPP4B (a negative regulator of phosphatidylinositol signaling) was 61% sensitive and 99% specific with the highest odds ratio (OR) at 108, indicating the strongest association with basal-like breast cancer. Expression of nestin, a common marker of neural progenitor cells that is also associated with the triple-negative/basal-like phenotype and poor breast cancer prognosis, possessed the second highest OR at 29 among the 46 biomarkers surveyed, as well as 54% sensitivity and 96% specificity. As a positively expressed biomarker, nestin possesses technical advantages over INPP4B that make it a more ideal biomarker for identification of basal-like breast cancer. The comprehensive immunohistochemical biomarker survey presented in this study is a necessary step for determining an optimized surrogate immunopanel that best defines basal-like breast cancer in a practical and clinically accessible way.

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Biomarkers for Basal-like Breast Cancer

Cited by 42 publications

References 170 publications

Molecular insights on basal-like breast cancer

Molecular insights on basal-like breast cancer

Immunohistochemical Differentiation of Triple Negative Breast Cancer

A survey of immunohistochemical biomarkers for basal-like breast cancer against a gene expression profile gold standard

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