Basal-Like Breast Cancer; Clinicopathological, Molecular, and Prognostic Features (original) (raw)
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Basal-like breast carcinoma: a phenotypically distinct entity
Archives of pathology & laboratory medicine, 2010
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 Breast Cancer: A Complex and Deadly Molecular Subtype
Current Molecular Medicine, 2012
During the last decade, gene expression profiling of breast cancer has revealed the existence of five molecular subtypes and allowed the establishment of a new classification. The basal subtype, which represents 15-25% of cases, is characterized by an expression profile similar to that of myoepithelial normal mammary cells. Basal tumors are frequently assimilated to triple-negative (TN) breast cancers. They display epidemiological and clinico-pathological features distinct from other subtypes. Their pattern of relapse is characterized by frequent and early relapses and visceral locations. Despite a relative sensitivity to chemotherapy, the prognosis is poor. Recent characterization of their molecular features, such as the dysfunction of the BRCA1 pathway or the frequent expression of EGFR, provides opportunities for optimizing the systemic treatment. Several clinical trials dedicated to basal or TN tumors are testing cytotoxic agents and/or molecularly targeted therapies. This review summarizes the current state of knowledge of this aggressive and hard-to-treat subtype of breast cancer.
Modern Pathology, 2011
Breast cancer is a heterogeneous disease encompassing a variety of entities with distinct morphological features and clinical behaviors. Although morphology is often associated with the pattern of molecular aberrations in breast cancers, it is also clear that tumors of the same histological type show remarkably different clinical behavior. This is particularly true for 'basal-like cancer', which is an entity defined using gene expression analysis. The purpose of this article was to review the current state of knowledge of basal-like breast cancers, to discuss the relationship between basal-like and triple-negative breast cancers, and to clarify practical implications of these diagnoses for pathologists and oncologists.
Basal phenotype breast cancer: implications for treatment and prognosis
Women's Health, 2011
Breast cancer is the most common malignancy in females. The origins and biology of breast carcinomas remain unclear. Cellular and molecular heterogeneity results in different distinct groups of tumors with different clinical behavior and prognosis. Gene expression profiling has delineated five molecular subtypes based on similarities in gene expression: luminal A, luminal B, HER2 overexpressing, normal-like and basal-like. Basal-like breast cancer (BLBC) lacks estrogen receptor, progesterone receptor and HER2 expression, and comprises myoepithelial cells. Specific features include high proliferative rate, rapid growth, early recurrence and decreased overall survival. BLBC is associated with ductal carcinoma in situ, BRCA1 mutation, brain and lung metastasis, and negative axillary lymph nodes. Currently, chemotherapy is the only therapeutic choice, but demonstrates poor outcomes. There is an overlap in definition between triple-negative breast cancer and BLBC due to the triple-negative profile of BLBC. Despite the molecular and clinical similarities, the two subtypes respond differently to neoadjuvant therapy. Although particular morphologic, genetic and clinical features of BLBC have been identified, a variety of definitions among studies accounts for the contradictory results reported. In this article the molecular morphological and histopathological profile, the clinical behavior and the therapeutic options of BLBC are presented, with emphasis on the discordant findings among studies.
Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma
2005
Microarray profiling of invasive breast carcinomas has identified five distinct subtypes of tumors (luminal A, luminal B, normal breast-like, HER2 overexpressing, and basal-like) that are associated with different clinical outcomes. The basal-like subtype is associated with poor clinical outcomes and is the subtype observed in BRCA1-related breast cancers. The aim of this study was to characterize the histologic and immunophenotypic properties of breast basal-like carcinomas that were first positively identified using DNA microarray analysis. Detailed histologic review was performed on 56 tumors with known microarray profiles (23 basal-like, 23 luminal, and 12 HER2 þ). Immunohistochemistry for estrogen receptor (ER), HER2, EGFR, smooth muscle actin (SMA), p63, CD10, cytokeratin 5/6, cytokeratin 8/18, and vimentin was performed on 18 basal-like, 16 luminal, and 12 HER2 þ tumors. The basal-like tumors were grade 3 ductal/NOS (21/23) or metaplastic (2/23) carcinomas that frequently showed geographic necrosis (17/23), a pushing border of invasion (14/23), and a stromal lymphocytic response (13/23). Most basal-like tumors showed immunoreactivity for vimentin (17/18), luminal cytokeratin 8/18 (15/18), EGFR (13/18), and cytokeratin 5/6 (11/18), while positivity for the myoepithelial markers SMA (4/18), p63 (4/18) and CD10 (2/18) was infrequent. All basal-like tumors tested were ERÀ and HER2À. Morphologic features significantly associated with the basal-like subtype included markedly elevated mitotic count (Po0.0001), geographic tumor necrosis (P ¼ 0.0003), pushing margin of invasion (P ¼ 0.0001), and stromal lymphocytic response (P ¼ 0.01). The most consistent immunophenotype seen in the basal-like tumors was negativity for ER and HER2, and positivity for vimentin, EGFR, cytokeratin 8/18, and cytokeratin 5/6. The infrequent expression of myoepithelial markers in basal-like carcinomas does not support a direct myoepithelial cell derivation of these tumors. These findings should further assist in the identification of basal-like carcinomas in clinical specimens, facilitating treatment and epidemiologic studies of this tumor subtype.
Modern Pathology, 2013
Basal-like invasive breast cancer is an important clinical group because of its association with a triple-negative phenotype defined by the lack of expression of estrogen, progesterone and human epidermal growth factor receptors 2, relative lack of therapeutic options and poor prognosis. However, depending on the method used to define these lesions, morphological assessment, immunohistochemical markers or gene expression, a different set of tumors is captured. The aim of this study was to investigate the consequences of using different methodological approaches to define basal-like lesions among triple-negative breast carcinomas with regard to their clinicopathological features and patient outcome. The cohort consisted of 142 invasive breast cancers with a triple-negative receptor status. First, each was reviewed histologically and those with morphological basallike features were characterized as 'Path-Basal'. Second, the 'Core Basal' immunohistochemical lesions, defined as cytokeratin 5/6 and/or epidermal growth factor receptor 1 positive, within the triple-negative breast cancers were identified, and third their classification based on gene expression profiling was retrieved and those in the molecular 'PAM50 basal-like' subtype recorded. A total of 116 basal-like breast cancers were identified among the 142 triple-negative breast cancers by at least one of these three classifications (80%), but only 13 samples were defined as basal-like with all three methods. None of these 13 tumors were associated with lymphovascular invasion. The 34 morphological 'Path-Basal' lesions were significantly associated with a lack of nodal metastases. Comparing the estimates of death in the three classifications, the highest risk of death was seen for the 'Core Basal' group. In this study, we highlight that the definition of basal-like breast cancer based on different methodologies varies significantly and does not identify the same lesions. This incomplete overlap of cases emphasizes the need for consistent or new approaches to improve precise identification.
Pathology Research International, 2011
Basal-like breast cancer, an aggressive subtype associated with high grade, poor prognosis, and younger age, is reported frequently in Africa. We analyzed the expression of the basal cytokeratins (CKs) 5/6 and 17 in a case series from Central Sudan and investigated correlations among basal CK status, ER, PgR, and Her-2/neu, and individual/clinicopathological data. Of 113 primary breast cancers 26 (23%), 38 (34%), and 46 (41%) were, respectively, positive for CK5/6, CK17, and combined basal CKs (CK5/6 and/or CK17). Combined basal CK+ status was associated with higher grade (P < .03) and inversely correlated with ER (P < .002), PgR (P = .004) and combined ER and/or PgR (P < .0002). Two clusters based on all tested markers were generated by hierarchical cluster analysis and k-mean clustering: I: designated "hormone receptors positive/luminal-like" and II: designated "hormone receptors negative", including both basal-like and Her-2/neu+ tumors. The most important factors for dataset variance were ER status, followed by PgR, CK17, and CK5/6 statuses. Overall basal CKs were expressed in a fraction of cases comparable to that reported for East and West African case series. Lack of associations with age and tumor size may represent a special feature of basal-like breast cancer in Sudan.
Basal-like breast cancer: molecular profiles, clinical features and survival outcomes
BMC medical genomics, 2017
Basal-like constitutes an important molecular subtype of breast cancer characterised by an aggressive behaviour and a limited therapy response. The outcome of patients within this subtype is, however, divergent. Some individuals show an increased risk of dying in the first five years, and others a long-term survival of over ten years after the diagnosis. In this study, we aim at identifying markers associated with basal-like patients' survival and characterising subgroups with distinct disease outcome. We explored the genomic and transcriptomic profiles of 351 basal-like samples from the METABRIC and ROCK data sets. Two selection methods, labelled Differential and Survival filters, were employed to determine genes/probes that are differentially expressed in tumour and control samples, and are associated with overall survival. These probes were further used to define molecular subgroups, which vary at the microRNA level and in DNA copy number. We identified the expression signatu...