Basal-like Breast Carcinomas Research Articles

ORIGINAL ARTICLE: Immunohistochemical identification of basal-like breast carcinoma and Its histopathologic correlation

Background and aim: DNA expression profiling studies of breast cancer have identified subtypes including luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) overexpression, and basal-like type. Among them, the basal-like type was associated with poor outcome. The purpose of this study was to classify breast carcinoma by immunohistochemistry and evaluate its characteristic histopathologic features. Methods: One hundred and four cases of resected infiltrating ductal carcinoma were immunostained for estrogen receptor, HER2, cytokeratin 5/6 and p63 to classification, and basal-like subtype were evaluated for its histopathologic characteristics. Results: The prevalence of subtypes was luminal A 48.1%, luminal B 24.0%, HER2 overexpression 11.5%, normal breast-like 4.8%, and basal-like 11.5%. There was significant correlation between the basal-like type and histologic grade. And it was significantly associated with several morphological features including expanding growth pattern, presence of tumor necrosis and peritumoral lymphocytic infiltration. Conclusions: The results of this study showed that the basal-like type occupied 11.5% of infiltrating ductal carcinoma and was associated with expanding growth pattern, presence of tumor necrosis and peritumoral lymphocytic infiltration.

Androgen receptor is frequently expressed in HER2-positive, ER/PR-negative breast cancers

The estrogen receptor (ER)/progesterone receptor (PR)-negative breast carcinomas (BCs) encompass three molecular subtypes: one with human epidermal growth factor receptor 2 (HER) overexpression, one normal like, and the triple negative. The androgen receptor (AR) is expressed in 70-90% of invasive BCs. The aim of our study is to detect the expression of AR in a series of ER/PR-negative BCs to ascertain if there is clinical significance in relation to BC molecular subtypes. A immunohistochemical study for all receptors and cytokeratin expression was performed in 232 cases of ER/PR-negative BCs. According to cytokeratin expression, BCs were classified into two groups: luminal-type BCs (44.2%) and basal-like-type BCs (55.8%). According to the expression of HER2, 59.3% were triple-negative BCs (when ER, PR, and HER2 were negative) and 40.7% were HER2-positive BCs. AR expression was observed in 128 tumors (56.6%). One hundred and ten cases (48.8%) had >10% and 18 (7.8%) had <10% of positively stained cells. AR immunoreactivity was found in 31.2% basal-like BCs, while in the luminal group 71.1% of cases were positive, showing highly significant correlation (p < 10⁻⁸). Regarding HER2 status, 76.7% of HER2-positive BC cases were AR positive compared with only 30.4% of triple-negative BC types, showing a strong statistically significant correlation. In conclusion, we show that AR is frequently expressed in ER/PR-negative BCs and that expression of HER2 and AR is highly correlated (p < 0.005). Our results point out the role of AR and HER2 in the pathogenesis of BCs and suggest the potential role of AR in clinical management of ER/PR-negative BCs.

P-cadherin, vimentin and CK14 for identification of basal-like phenotype in breast carcinomas: an immunohistochemical study.

The most suitable immunohistochemical criterion to identify basal-like breast carcinomas (BLBC), a molecular subgroup of breast cancer associated with poor prognosis, is the triple negative phenotype along with CK5 and/or EGFR immunoreactivity. However, several putative basal markers have been suggested as alternatives to identify BLBC with more accuracy. The expression of CK5, EGFR, P-cadherin, CK14, Vimentin and p63 were evaluated in 462 invasive breast carcinomas to determine their sensitivity and specificity for BLBC identification. P-cadherin and CK5 showed higher sensitivity values, while EGFR, Vimentin and CK14 were the most specific markers. The combination of CK5 with P-cadherin, Vimentin or CK14 proved to be a reliable option for distinguishing the basal phenotype, compared to the "gold standard" pair CK5/EGFR. Furthermore, P-cadherin was still able to recognize a large number of putative BLBC among the "unclassified" group (ER-/PR-/HER2-/CK5-/EGFR-). P-cadherin, Vimentin and CK14 can recognize BLBC already identified in triple negative/ CK5 and/or EGFR+ tumors, and due to P-cadherin sensitivity for BLBC identification this marker can reliably recruit a large number of breast carcinomas with basal phenotype among immunohistochemistry triple negative/ CK5 and/or EGFR - pool of tumors. Although they need GEP validation, our results can introduce the idea of these markers as additional options in the daily workup of breast pathology laboratories to identify BLBC.

The Met oncogene and basal-like breast cancer: another culprit to watch out for?

Recent findings suggest the involvement of the MET oncogene, encoding the tyrosine kinase receptor for hepatocyte growth factor, in the onset and progression of basal-like breast carcinoma. The expression profiles of basal-like tumors - but not those of other breast cancer subtypes - are enriched for gene sets that are coordinately over-represented in transcriptional signatures regulated by Met. Consistently, tissue microarray analyses have revealed that Met immunoreactivity is much higher in basal-like cases of human breast cancer than in other tumor types. Finally, mouse models expressing mutationally activated forms of Met develop a high incidence of mammary tumors, some of which exhibit basal characteristics. The present review summarizes current knowledge on the role and activity of Met in basal-like breast cancer, with a special emphasis on the correlation between this tumor subtype and the cellular hierarchy of the normal mammary gland.

Pathway-focused proteomic signatures in HER2-overexpressing breast cancer with a basal-like phenotype: New insights into de novo resistance to trastuzumab (Herceptin)

Pioneering clinical studies in de novo refractoriness to the anti-HER2 monoclonal antibody trastuzumab have suggested that HER2 gene-amplification can take place also in a basal-like molecular background to generate basal/HER2+ tumors intrinsically resistant to trastuzumab. Here, we first investigated the unique histogenesis of the basal/HER2+ phenotype in breast carcinomas. The presence of basal CK5/CK6 cytokeratin expression in HER2+ tumors revealed a significant overlap in the histological features of HER2+/CK5/6+ and basal-like breast carcinomas. Basal/HER2+ tumors were typically poorly differentiated, high-grade invasive ductal carcinomas with large geographic necrosis, pushing margins of invasion, syncytial arrangement of tumor cells, ribbon- or festoon-like architecture, squamous metaplasia, stromal lymphocytic infiltrates, high mitotic index and strong p53 positivity. Secondly, we performed low-scale proteomic approaches in JIMT-1 cells, a unique model of HER2-gene amplified trastuzumab-resistant breast carcinoma with a basal-like phenotype, to develop biomarker signatures that may differentiate trastuzumab-responsive from non-responsive tumors. When applying antibody-based array technology to the extracellular milieu of trastuzumab-refractory JIMT-1 and trastuzumab-sensitive SKBR3 cell cultures, JIMT-1 cells were found to secrete higher amounts of several growth factors including amphiregulin, EGF, IGFBP-6, PDGF-AA, neurotrophins, TGFbeta and VEGF. Semi-quantitative signaling node multi-target sandwich ELISAs revealed that JIMT-1 cells drastically overactivate RelA, the prosurvival subunit of NF-kappaB as compared to trastuzumab-sensitive luminal/HER2+ SKBR3 cells. When simultaneously assessing the activation status of 42 receptor tyrosine kinases (RTK) using a human phospho-RTK array, JIMT-1 cells were found to constitutively display hyperactivation of the insulin-like growth factor-I receptor (IGF-1R). High-content immunofluorescence imaging revealed that activated IGF-1R mainly localized at focal adhesion-like structures in JIMT-1 cells. In vitro wound healing assays suggested that this functional reorganization of the JIMT-1 cytoskeletal reorganization may account for an exacerbated trastuzumab-refractory 'migratogenic' phenotype. Forthcoming studies should validate the notion that identification of basal-like immunophenotypes and/or basal-like molecular signatures within HER2+ breast carcinomas may provide rapid means to define subgroups of breast cancer patients likely to display resistance to trastuzumab ab initio.

Monocarboxylate transporter 1 is up‐regulated in basal‐like breast carcinoma

Monocarboxylate transporters (MCTs) have been considered promising targets for cancer therapy, since they facilitate lactate efflux in glycolytic tumours. However, their role in solid tumours is still poorly understood. Thus, the present work aimed to contribute to understanding the involvement of MCT1 and MCT4 in breast cancer progression as well as MCT regulation by CD147. The expression of the membrane transporters MCT1 and MCT4 was analysed in a series of breast carcinomas (249 cases) and their clinicopathological significance investigated. Additionally, we analysed the significance of CD147 co-expression, as an important regulator of MCT expression and activity. MCT1 was significantly increased in breast carcinomas when compared with normal breast tissue and, importantly, both MCT1 and CD147 were associated with poor prognostic variables such as basal-like subtype and high grade tumours. These results provide evidence for a prognostic value of MCT1 in breast carcinoma and support the exploitation of the complex MCT1/CD147 as a promising target for cancer therapy, especially in basal-like breast carcinoma.

Abstract 795: SOX2: profiling a new group of breast cancer patients with poor prognosis

Abstract SOX2 - the SRY (sex determining region Y)-box 2 transcription factor, as the key trigger in maintaining pluripotency in embryonic stem cells has shown to be up regulated in a variety of human breast cancers and especially in basal-like breast carcinomas. Aim of this morphologic study was to combine SOX2 immunohistochemical positive cases with their histopathological data to selected markers used already in daily diagnosis and combine those results to create a possible ‘SOX2 staining profile’ confirming poor prognosis within this group of patients. Poor prognosis in this context was defined on histopathological criteria as high grade/poorly differentiated invasive tumours with high stage and preferable basal-like phenotype with invasive lobular carcinomas possessing better prognosis instead of invasive ductal carcinomas. Also carcinomas with mesenchymal phenotype and high proliferation rate correlate with a much worse outcome. A collective of 20 invasive breast cancer patients selected from a 86 breast cancer cohort as well as 5 cases of non-malignant tissue from breast hypertrophy were immunohistochemically stained using formalin-fixed paraffin-embedded tissue samples and primary antibodies against SOX2 and 10 selected markers (β-catenin, CK5/6, Cyclin D1, EGFR, ER, Her2, Nanog, Oct-4, PR, Vimentin) known to be of prognostic values. 6 breast cancer cell lines (MCF-7, MDA-MB231, MDA-MB453, SK-BR3, SUM-159, T47-D) and 2 breast epithelial-like cell lines (MCF-10A, MCF-12A) provided as formalin-fixed paraffin-embedded cytoblocks were additionally analysed and characterized on a immunocytochemical level with identical markers. The markers used in this assay were beyond β-catenin as the activating partner of SOX2, Nanog and Oct-4 as important drivers of “stemness”, PR, ER and Her2 together with CK5/6 and EGFR to decrypt breast carcinomas with basal-like phenotype and finally Vimentin as a mesenchymal marker and CyclinD1 for illustrating cells into G1/S transition. During our investigations SOX2 revealed to be associated to patients with high grade (75%G3; 25%G2), stage (64,3% &amp;gt;T2) and in the majority of patients to a basal-like phenotype (42.3%). Interestingly SOX2 staining also referred strictly to invasive ductal carcinomas instead of invasive lobular carcinomas, mixed types or other tumoral subtypes. Within the SOX2 positive cases Vimentin and CK5/6 expression is correlated mainly to basal-like carcinomas demonstrating this tumor subclass is probably derived from a much more primitive, less differentiated progenitor or even stem-like pool of cells. Concerning the utilized breast cancer cell lines, these trends could also be verified on a cellular level. These findings suggest that SOX2 expression is generally linked to a subpopulation of breast cancer patients with poor prognosis. These results could be of potential value for further investigations concerning targeted therapy onset on SOX2 pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 795.

Abstract PL1-1: Genomic architecture characterizes tumor progression paths and fate in breast cancer patients

Abstract Breast cancer is a heterogeneous disease as reflected by histopathology, molecular alterations and clinical behavior. In order to relate cellular and sub-cellular features to clinical parameters and outcome, substantial effort has been exerted towards identifying tumor groups with distinct molecular features. The gene expression based classification that we proposed ten years ago identified five different subgroups with difference in survival; two Luminal-cell related groups (Luminal A and luminal B), a myoepithelial-cell related group (Basal-like), a HER2 enriched, and a Normal-like group. The Basal-like and Luminal carcinomas have different etiologies and for most purposes may be considered as distinct diseases. This is also reflected in the genomic portraits defined by aCGH (array Comparative Genomic Hybridization), and it seems evident that the history of the molecular subgroups is written in the DNA alterations. We have developed two platform independent algorithms to explore genomic architectural distortion using aCGH data to measure whole arm gains and losses (WAAI) and complex rearrangements (CAAI). By applying CAAI and WAAI to data from 595 breast cancer patients we were able to separate the cases into eight subgroups with different distribution of genomic distortion. Within each subgroup data from expression analyses, sequencing and ploidy indicated that progression occurs along separate paths into more complex genotypes. Several of the CGH based subgroups were enriched for either luminal related or basal related tumors, and showed distinct patterns of genomic alterations. In particular, basal related tumors were separated into genomic classes with distinct patterns of alterations emphasizing genomic heterogeneity also in this expression subclass. Histological grade had prognostic impact only in the Luminal related groups while the complexity identified by CAAI had an overall independent prognostic power. These results emphasizes the relationship between structural genomic alterations, expression subtypes and clinical behavior, and provides a score of genomic complexity as a new tool for prognostication in breast cancer. Using SNP arrays and a novel bioinformatic approach, ASCAT (Allele-Specific Copy number Analysis of Tumors), we have performed genome wide allele-specific copy number analysis of 112 breast cancer genomes. We were able to accurately dissect the allele-specific copy number in each tumor, simultaneously estimating and adjusting for both tumor ploidy and non-aberrant cell admixture, allowing calculation of “Tumor Profiles” (genome-wide allele-specific copy-number profiles) from which gains, losses, copy-number-neutral events and LOH could be determined. The tumors had on average a non-aberrant cell admixture of 49%, and 45% of them were aneuploid (&amp;gt;2.7n). By aggregation of Tumor Profiles across the sample set a genome-wide view of LOH and copy-number-neutral events was obtained. The Tumor Profiles also revealed differences in aberrant tumor cell fraction, ploidy, gains, losses, LOH and copy-number-neutral events between the five expression subtypes. Basal-like breast carcinomas have a significantly higher frequency of LOH compared to other subtypes, and their Tumor Profiles show large-scale loss of genomic material during tumor development, followed by a whole-genome duplication, resulting in near-triploid genomes. From the Tumor Profiles we could also construct a genome-wide map of allelic skewness, indicating loci where one allele is preferentially lost while the other allele is preferentially gained. We hypothesize that these alternative alleles have a different influence on breast carcinoma development. Citation Information: Clin Cancer Res 2010;16(7 Suppl):PL1-1

Basal-like breast carcinoma: a phenotypically distinct entity.

Gene microarray profiling of human breast carcinomas has recently categorized invasive breast carcinomas into 5 distinct subtypes; luminal A, luminal B, normal breastlike, human epithelial growth factor receptor 2 (HER2) overexpressing, and basal-like. Basal-like breast carcinomas are characterized by high expression of basal cytokeratins; low or absent expression of estrogen receptor, progesterone receptor, and HER2/neu; and expression of epidermal growth factor receptor (EGFR) and/or c-kit, and they are frequently associated with breast cancer 1 (BRCA1) mutations and poor clinical outcome. Recent studies have begun to provide insights into the molecular genetics, biology, morphology, and clinical outcome of this subtype of breast carcinoma. We reviewed the literature related to basal-like breast carcinomas to better understand this clinically significant subtype of breast carcinoma.

Basal-like Breast Carcinoma: A Phenotypically Distinct Entity

Gene microarray profiling of human breast carcinomas has recently categorized invasive breast carcinomas into 5 distinct subtypes; luminal A, luminal B, normal breastlike, human epithelial growth factor receptor 2 (HER2) overexpressing, and basal-like. Basal-like breast carcinomas are characterized by high expression of basal cytokeratins; low or absent expression of estrogen receptor, progesterone receptor, and HER2/neu; and expression of epidermal growth factor receptor (EGFR) and/or c-kit, and they are frequently associated with breast cancer 1 (BRCA1) mutations and poor clinical outcome. Recent studies have begun to provide insights into the molecular genetics, biology, morphology, and clinical outcome of this subtype of breast carcinoma. We reviewed the literature related to basal-like breast carcinomas to better understand this clinically significant subtype of breast carcinoma.

Most basal-like breast carcinomas demonstrate the same Rb−/p16+ immunophenotype as the HPV-related poorly differentiated squamous cell carcinomas which they resemble morphologically

Most basal-like breast carcinomas demonstrate the same Rb−/p16+ immunophenotype as the HPV-related poorly differentiated squamous cell carcinomas which they resemble morphologically

Triple-negative breast carcinomas are a heterogeneous entity that differs between young and old patients

OBJECTIVE:To compare the frequency and immunohistochemical profiles of triple‐negative breast carcinomas in younger and older women.METHODS AND RESULTS:We selected patients diagnosed with triple‐negative breast carcinomas. The groups examined were women who were 35 years old or younger between 1997 and 2007 (n = 74) and, for comparison, women who were 60 years old or older (n = 19, consecutive cases). All formalin‐fixed and paraffin‐embedded tumor samples were reviewed and immunohistochemically stained for ER, PR, HER2, Ki‐67 antigen, epidermal growth factor receptor, cytokeratin 5/6, p53, vimentin, CD117, and p63 using tissue microarrays blocks. Triple‐negative breast carcinomas corresponded to 34.6% (74/213) of the carcinomas from the younger patients and 16.2% (19/117) of the carcinomas from the older patients (p = 0.002). No significant differences in the frequency of the basal phenotype were observed in the two patient groups based on CK5/6 and/or epidermal growth factor receptor expression (74.3% vs. 68.4%). However, triple‐negative breast carcinomas in the older patients presented a higher frequency of CK5/6 expression compared to those of younger patients (42.1% vs. 9.6%; p = 0.005), whereas triple‐negative breast carcinomas of younger patients had a higher expression level of epidermal growth factor receptor (71.6% vs. 47.3%).CONCLUSIONS:These results show that there were significant molecular differences between the triple‐negative basal‐like breast carcinomas that were diagnosed in younger women and those that were diagnosed in older women. These findings may provide a basis for describing the more aggressive phenotype of the triple‐negative breast carcinomas observed in younger women.

Effects of Astragalus injection and its ingredients on proliferation and Akt phosphorylation of breast cancer cell lines

To observe the effects of Astragalus injection, astragaloside IV and formononetin on proliferation and Akt phosphorylation of basal-like human breast carcinoma cell lines MDA-MB-468 and MDA-MB-231. The effects of different concentrations of Astragalus injection, astragaloside IV and formononetin on proliferation of breast cancer cell lines were assayed by methyl thiazolyl tetrazolium (MTT) assay, and their effects on phospho-Akt were assayed by in-cell Western blot method. The results of the MTT assay showed that the best concentrations of Astragalus injection, astragaloside IV, formononetin and astragaloside IV plus formononetin were 1 g/mL, 80 microg/mL, 40 microg/mL and 10 microg/mL plus 40 microg/mL respectively. After 1- or 2-day culture, Astragalus injection, astragaloside IV, formononetin and astragaloside IV plus formononetin decreased the expressions of p-Akt (Thr 308) and p-Akt (Ser 473) in MDA-MB-468 cells. Formononetin and astragaloside IV plus formononetin down-regulated the expression of p-Akt (Thr 308) protein in MDA-MB-231 cells after 1- and 2-day culture, but had no effects on the expression of p-Akt (Ser 473) protein in MDA-MB-231 cells. Astragalus injection, astragaloside IV and formononetin can inhibit proliferation of breast cancer cell lines MDA-MB-468 and MDA-MB-231, and the antiproliferation effects vary according to their concentrations. And the antiproliferation mechanisms may be related to their down-regulation effects on Akt phosphorylation.

Microglandular adenosis or microglandular adenoma? A molecular genetic analysis of a case associated with atypia and invasive carcinoma

Microglandular adenosis (MGA) is a rare breast lesion, which has long been considered to be hyperplastic. However, atypical forms of MGA (AMGA) and invasive carcinomas arising in the background of MGA are recorded. Recent studies have suggested that MGA may be a non-obligate precursor of invasive carcinomas that are negative for hormone receptors and lack HER-2 overexpression (triple-negative phenotype). The aim of this study was to determine whether MGA is clonal and whether it harbours chromosomal aberrations similar to those found in matched invasive ductal carcinoma of no special type (IDC-NST). We report on a case comprising MGA, AMGA and a high-grade IDC-NST. The three components were separately microdissected and subjected to genetic analysis with high-resolution microarray comparative genomic hybridisation. Identical genetic changes were detected in all components with subsequent acquisition of additional genetic aberrations in the invasive component, suggesting that MGA was the substrate for the development of the invasive carcinoma. Immunohistochemistry revealed concordant profiles across all components, characterized by triple-negative phenotype and variable positivity for basal markers. Similar to adenomas, MGA is, at least in some cases, a clonal lesion and may be a non-obligate precursor of a subgroup of high-grade triple-negative and basal-like breast carcinomas.

Elevated expression of phosphorylated c-Jun NH2-terminal kinase in basal-like and “triple-negative” breast cancers

Basal-like carcinomas and human epidermal growth factor receptor 2 (HER-2/neu) overexpression carcinomas are the subgroups of breast cancers that have the most aggressive clinical behavior. Phosphorylation/activation of c-Jun NH2-terminal kinase is characterized as a stress-activated protein kinase, which regulates apoptosis after cellular stress. The aim of this study was to evaluate the association of phosphorylated c-Jun NH2-terminal kinase expression with phenotypes and clinicopathologic parameters of breast cancer. Phosphorylated c-Jun NH2-terminal kinase was immunohistochemically measured in a cohort of 160 patients with invasive breast cancer treated with therapeutic surgery followed by anthracycline or docetaxel-based chemotherapy. These results were further correlated with the phenotypes and clinicopathologic characteristics of breast cancers. Increased phosphorylated c-Jun NH2-terminal kinase expression was significantly associated with lack of estrogen receptor expression (P < .0001), positivity for cytokeratins 5/6 (P = .029), epidermal growth factor receptor (P = .035), basal-like phenotype (P = .015), and "triple-negative" phenotype (P = .01). Furthermore, the positive expression of phosphorylated c-Jun NH2-terminal kinase was positively correlated with p-glycoprotein (r = 0.54, P < .0001) and multidrug resistance-associated protein 1(r = 0.38, P < .0001) but not with lung resistance protein (r = -0.02, P = .78). Our results indicate that the activation of phosphorylated c-Jun NH2-terminal kinase may play a role in the carcinogenesis of basal-like and triple-negative breast carcinoma.

Carcinoma of the Breast With Medullary-like Features: Diagnostic Challenges and Relationship With BRCA1 and EZH2 Functions

This case presentation reviews the histologic distinction between pure medullary carcinoma and breast carcinomas with medullary-like features. This particular case prompts us to analyze the relationship among medullary carcinoma, basal-like breast carcinomas and carcinomas associated with germline BRCA1 mutations. In addition to now well-defined features, such as expression of high-molecular-weight cytokeratins and EGFR (epidermal growth factor receptor), basal-like tumors have a deficiency or dysfunction of BRCA1. This association in part explains the histologic features of BRCA1-associated breast cancers. Recent studies in our laboratory demonstrate that BRCA1 protein is regulated by a recently described gene, EZH2. These concepts illustrate the important relationships among histopathologic features; genomic profile; single gene abnormalities, such as BRCA1 and EZH2; and growth regulation in this subset of breast carcinomas.

Basal-like Breast Carcinoma: From Expression Profiling to Routine Practice

Abstract Context.—Advances in the understanding of the molecular and genetic mechanisms of breast cancer have led to realization of the heterogeneity of the disease and the promise of a new era of individualized management for patients with breast cancer. The advent and use of high-throughput molecular methods for the study of breast cancer have brought to the forefront the existence of the so-called basal-like breast cancers, which have been shown to have distinct biologic and clinical characteristics. Objective.—To critically assess the clinicopathologic features of basal-like breast cancer, discuss the morphologic and immunophenotypic features of basal-like cancer, and explore the criteria that can be used to identify these tumors in routine practice. Data Sources.—A Medline/PubMed search was conducted using the terms “basal-like,” “(basal OR basaloid OR basal-like) AND breast cancer.” All articles in English language were retrieved and critically reviewed. Conclusions.—Basal-like breast cancers consti...

P1128 Possible relation between basal-like breast carcinoma and woman's age

International Journal of Gynecology & ObstetricsVolume 107, Issue S2 p. S728-S728 Poster presentations P1128 Possible relation between basal-like breast carcinoma and woman's age A. Polidoro, A. PolidoroSearch for more papers by this authorR. Dufloth, R. DuflothSearch for more papers by this authorD. Vieira, D. VieiraSearch for more papers by this authorL. Zeferino, L. ZeferinoSearch for more papers by this authorF. Schmitt, F. SchmittSearch for more papers by this author A. Polidoro, A. PolidoroSearch for more papers by this authorR. Dufloth, R. DuflothSearch for more papers by this authorD. Vieira, D. VieiraSearch for more papers by this authorL. Zeferino, L. ZeferinoSearch for more papers by this authorF. Schmitt, F. SchmittSearch for more papers by this author First published: 20 November 2009 https://doi.org/10.1016/S0020-7292(09)62612-6AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume107, IssueS2Abstracts of XIX FIGO World Congress of Gynecology and ObstetricsOctober 2009Pages S728-S728 RelatedInformation

O1043 The investigation of specific immunohistochemical markers to distinguish basal-like invasive breast carcinoma

O1043 The investigation of specific immunohistochemical markers to distinguish basal-like invasive breast carcinoma

Current data of targeted therapies for the treatment of triple-negative advanced breast cancer: empiricism or evidence-based?

Approximately 10 – 15% of breast carcinomas (BCs) are known to be ‘triple–negative (TN) receptor’ (i.e., not expressing ER or PR and not exhibiting overexpression and/or gene amplification of HER2-neu). Triple-negative BCs comprise approximately 85% of all basal-type tumours. Classically, basal-like BCs have been characterised by low expression of ER, PR, and HER2 neu and high expression of CK5, CK14, caveolin-1, CAIX, p63, and EGFR (HER1), which reflects the mammary gland basal/myoepithelial cell component. Although there is no standard first-line chemotherapy regimen for metastatic TN BCs, anthracycline- and taxane-containing regimens are acceptable treatments. A large number of agents, including DNA-damaging agents, EGFR inhibitors, antiangiogenic agents and novel taxane formulations are currently being tested in clinical trials for first-line and pretreated patients. Limited experiences with platinum salts, poly(ADP-ribose) polymerase (PARP) inhibitors, cetuximab, bevacizumab and ixabepilone have been published in recent years and will be reported. Novel immunohistochemistry analysis for identification of basal like/TN phenotype are awaited to correctly select this population. The clinical trials investigating new agents have to be designed for a specific (and possibly large) subset of patients with BC. In the future, a gene array platform with greater sensitivity for distinguishing the various BC subtypes, as well as having the power to predict the molecular biology of the disease, will be an indispensible tool for treatment selection. Currently, treatment of TN BC is more empirical than evidence-based. The cornerstone of treatment is chemotherapy, but in the near future, novel target agents will emerge as possible partners.