Basal Breast Cancer: A Complex and Deadly Molecular Subtype

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.

[1]  W. Foulkes,et al.  A Basal Epithelial Phenotype Is More Frequent in Interval Breast Cancers Compared with Screen Detected Tumors , 2005, Cancer Epidemiology Biomarkers & Prevention.

[2]  C. Sotiriou,et al.  Taking gene-expression profiling to the clinic: when will molecular signatures become relevant to patient care? , 2007, Nature Reviews Cancer.

[3]  D. Birnbaum,et al.  Cancer Stem Cells in Breast: Current Opinion and Future Challenges , 2008, Pathobiology.

[4]  Ash A. Alizadeh,et al.  Gene Expression Signature of Fibroblast Serum Response Predicts Human Cancer Progression: Similarities between Tumors and Wounds , 2004, PLoS biology.

[5]  S. Furuta,et al.  Depletion of BRCA1 impairs differentiation but enhances proliferation of mammary epithelial cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[6]  A. Gown,et al.  Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma , 2004, Clinical Cancer Research.

[7]  J. Benítez,et al.  Prognostic Significance of Basal-Like Phenotype and Fascin Expression in Node-Negative Invasive Breast Carcinomas , 2006, Clinical Cancer Research.

[8]  M. Cronin,et al.  A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. , 2004, The New England journal of medicine.

[9]  F. Cognetti,et al.  HER2 and response to paclitaxel in node-positive breast cancer. , 2008, The New England journal of medicine.

[10]  M. J. van de Vijver,et al.  Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[11]  Achim Rody,et al.  T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers , 2009, Breast Cancer Research.

[12]  E. Winer,et al.  A phase II trial of the PARP inhibitor veliparib (ABT888) and temozolomide for metastatic breast cancer. , 2010 .

[13]  Jason I. Herschkowitz,et al.  Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer , 2010, Breast Cancer Research.

[14]  John W M Martens,et al.  Subtypes of breast cancer show preferential site of relapse. , 2008, Cancer research.

[15]  C. Perou,et al.  AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer. , 2005, The Journal of clinical investigation.

[16]  S. Narod,et al.  Time to disease recurrence in basal‐type breast cancers , 2009, Cancer.

[17]  Shridar Ganesan,et al.  X chromosomal abnormalities in basal-like human breast cancer. , 2006, Cancer cell.

[18]  M. Fernö,et al.  Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers , 2007, Breast Cancer Research.

[19]  W. Foulkes.  BRCA1 functions as a breast stem cell regulator , 2004, Journal of Medical Genetics.

[20]  C. Perou,et al.  Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  Gianluca Bontempi,et al.  Biological Processes Associated with Breast Cancer Clinical Outcome Depend on the Molecular Subtypes , 2008, Clinical Cancer Research.

[22]  A. Ashworth,et al.  Targeting the DNA repair defect of BRCA tumours. , 2005, Current opinion in pharmacology.

[23]  C. Perou,et al.  Epidemiology of basal-like breast cancer , 2008, Breast Cancer Research and Treatment.

[24]  Harry Bartelink,et al.  Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas , 2007, Breast Cancer Research.

[25]  P. Johnston,et al.  The role of BRCA1 in the cellular response to chemotherapy. , 2004, Journal of the National Cancer Institute.

[26]  G. Sherlock,et al.  The prognostic role of a gene signature from tumorigenic breast-cancer cells. , 2007, The New England journal of medicine.

[27]  G. Hortobagyi,et al.  Overview of resistance to systemic therapy in patients with breast cancer. , 2007, Advances in experimental medicine and biology.

[28]  Yudong D. He,et al.  Gene expression profiling predicts clinical outcome of breast cancer , 2002, Nature.

[29]  A. Nobel,et al.  Supervised risk predictor of breast cancer based on intrinsic subtypes. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  Z. Szallasi,et al.  Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  Yudi Pawitan,et al.  Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients , 2006, Breast Cancer Research.

[32]  C. Perou,et al.  Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. , 2006, JAMA.

[33]  F. Heitz,et al.  Cerebral metastases (CM) in breast cancer (BC) with focus on triple-negative tumors , 2008 .

[34]  D. Dabbs,et al.  Basal phenotype of ductal carcinoma in situ: recognition and immunohistologic profile , 2006, Modern Pathology.

[35]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Daniel Birnbaum,et al.  Poly(ADP-ribose) polymerase-1 mRNA expression in human breast cancer: a meta-analysis , 2011, Breast Cancer Research and Treatment.

[37]  C. Perou,et al.  Identification of a basal-like subtype of breast ductal carcinoma in situ. , 2007, Human pathology.

[38]  S. Tavaré,et al.  High-resolution aCGH and expression profiling identifies a novel genomic subtype of ER negative breast cancer , 2007, Genome Biology.

[39]  F. B. Sørensen,et al.  Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[40]  Carlos Caldas,et al.  A robust classifier of high predictive value to identify good prognosis patients in ER-negative breast cancer , 2008, Breast Cancer Research.

[41]  E. Álava,et al.  Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer , 2010, Breast Cancer Research and Treatment.

[42]  Charles M Perou,et al.  The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas , 2008, Breast Cancer Research.

[43]  L. Carey.  Directed therapy of subtypes of triple-negative breast cancer. , 2010, The oncologist.

[44]  Karen A Gelmon,et al.  Population-based validation of the prognostic model ADJUVANT! for early breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  C. Perou,et al.  Interactions with Fibroblasts Are Distinct in Basal-Like and Luminal Breast Cancers , 2010, Molecular Cancer Research.

[46]  S. Leung,et al.  Basal breast cancer molecular subtype predicts for lower incidence of axillary lymph node metastases in primary breast cancer. , 2008, Clinical breast cancer.

[47]  Wolfgang Heller,et al.  Triple-negative breast cancer: therapeutic options. , 2007, The Lancet. Oncology.

[48]  A. Ashworth,et al.  Basal-like breast carcinomas: clinical outcome and response to chemotherapy , 2006, Journal of Clinical Pathology.

[49]  F. Bertucci,et al.  BARD1 homozygous deletion, a possible alternative to BRCA1 mutation in basal breast cancer , 2010, Genes, chromosomes & cancer.

[50]  M. Jasin,et al.  Homology-directed dna repair, mitomycin-c resistance, and chromosome stability is restored with correction of a Brca1 mutation. , 2001, Cancer research.

[51]  Martin Eisenacher,et al.  Cytogenetic Alterations and Cytokeratin Expression Patterns in Breast Cancer: Integrating a New Model of Breast Differentiation into Cytogenetic Pathways of Breast Carcinogenesis , 2002, Laboratory Investigation.

[52]  Roman Rouzier,et al.  Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy , 2005, Clinical Cancer Research.

[53]  R. Weichselbaum,et al.  The Breast Cancer Susceptibility Gene BRCA1 Is Required for Subnuclear Assembly of Rad51 and Survival following Treatment with the DNA Cross-linking Agent Cisplatin* , 2000, The Journal of Biological Chemistry.

[54]  M. García-Closas,et al.  Differences in Risk Factors for Breast Cancer Molecular Subtypes in a Population-Based Study , 2007, Cancer Epidemiology Biomarkers & Prevention.

[55]  C. Perou,et al.  The Triple Negative Paradox: Primary Tumor Chemosensitivity of Breast Cancer Subtypes , 2007, Clinical Cancer Research.

[56]  C. Perou,et al.  Population differences in breast cancer: survey in indigenous African women reveals over-representation of triple-negative breast cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[57]  A. Nobel,et al.  The molecular portraits of breast tumors are conserved across microarray platforms , 2006, BMC Genomics.

[58]  Peter Kraft,et al.  Heterogeneity of Breast Cancer Associations with Five Susceptibility Loci by Clinical and Pathological Characteristics , 2008, PLoS genetics.

[59]  P. Bonnier,et al.  Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype. , 2007, Human pathology.

[60]  C. Perou,et al.  TBCRC 001: EGFR inhibition with cetuximab added to carboplatin in metastatic triple-negative (basal-like) breast cancer , 2008 .

[61]  N. Harbeck,et al.  Triple-negative high-risk breast cancer derives particular benefit from dose intensification of adjuvant chemotherapy: results of WSG AM-01 trial. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[62]  Daniel Birnbaum,et al.  Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. , 2006, Cancer research.

[63]  H. Rugo,et al.  Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[64]  A. Bednarek,et al.  Prognostic Relevance of Basal Cytokeratin Expression in Operable Breast Cancer , 2006, Oncology.

[65]  Haiyan I. Li,et al.  Purification and unique properties of mammary epithelial stem cells , 2006, Nature.

[66]  C. Perou,et al.  In Vitro and In Vivo Analysis of B-Myb in Basal-Like Breast Cancer , 2008, Oncogene.

[67]  A. Rosenberg,et al.  Differences in breast carcinoma characteristics in newly diagnosed African–American and Caucasian patients , 2007, Cancer.

[68]  Karla Kerlikowske,et al.  Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors. , 2007, Cancer cell.

[69]  A. Richardson,et al.  BRCA1 promoter methylation in sporadic breast tumors: relationship to gene expression profiles , 2005, Breast Cancer Research and Treatment.

[70]  R. Tibshirani,et al.  Copyright © American Society for Investigative Pathology Short Communication Expression of Cytokeratins 17 and 5 Identifies a Group of Breast Carcinomas with Poor Clinical Outcome , 2022 .

[71]  Philip M. Long,et al.  Breast cancer classification and prognosis based on gene expression profiles from a population-based study , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[72]  T. Sørlie,et al.  Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms , 2006, BMC Genomics.

[73]  G. Mills,et al.  Incidence and Outcome of BRCA Mutations in Unselected Patients with Triple Receptor-Negative Breast Cancer , 2011, Clinical Cancer Research.

[74]  J. Kwon,et al.  Expanding the criteria for BRCA mutation testing in breast cancer survivors. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[75]  Douglas Macmillan,et al.  Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance. , 2006, European journal of cancer.

[76]  Charles M Perou,et al.  Breast carcinomas arising at a young age: unique biology or a surrogate for aggressive intrinsic subtypes? , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[77]  J. Gralow,et al.  Current treatment options in triple negative breast cancer. , 2010, Breast disease.

[78]  S. Narod,et al.  Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence , 2007, Clinical Cancer Research.

[79]  F. Bertucci,et al.  Moesin expression is a marker of basal breast carcinomas , 2007, International journal of cancer.

[80]  Caroline Seynaeve,et al.  Distant disease-free interval, site of first relapse and post-relapse survival in BRCA1- and BRCA2-associated compared to sporadic breast cancer patients , 2008, Breast Cancer Research and Treatment.

[81]  P. Johnston,et al.  BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. , 2003, Cancer research.

[82]  J. O’Shaughnessy,et al.  Preliminary results of a randomized phase II study of weekly irinotecan/carboplatin with or without cetuximab in patients with metastatic breast cancer , 2007 .

[83]  Raymond R Tubbs,et al.  Breast Cancers With Brain Metastases are More Likely to be Estrogen Receptor Negative, Express the Basal Cytokeratin CK5/6, and Overexpress HER2 or EGFR , 2006, The American journal of surgical pathology.

[84]  Daniel Birnbaum,et al.  Integrated profiling of basal and luminal breast cancers. , 2007, Cancer research.

[85]  J. Lubiński,et al.  Preliminary safety and activity results of trabectedin in a phase II trial dedicated to triple-negative (ER-, PR-, HER2-), HER2+++, or BRCA1/2 germ-line-mutated metastatic breast cancer (MBC) patients (pts). , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[86]  M. J. van de Vijver,et al.  Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. , 2006, Journal of the National Cancer Institute.

[87]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[88]  R. Arriagada,et al.  Breast cancer molecular subclassification and estrogen receptor expression to predict efficacy of adjuvant anthracyclines-based chemotherapy: a biomarker study from two randomized trials. , 2007, Annals of oncology : official journal of the European Society for Medical Oncology.

[89]  Daniel Birnbaum,et al.  Basal and luminal breast cancers: basic or luminous? (review). , 2004, International journal of oncology.

[90]  J. Foekens,et al.  Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer , 2005, The Lancet.

[91]  Philippe Dessen,et al.  Molecular Characterization of Breast Cancer with High-Resolution Oligonucleotide Comparative Genomic Hybridization Array , 2009, Clinical Cancer Research.

[92]  Barbara L. Smith,et al.  Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[93]  I. Ellis,et al.  Triple‐negative/basal‐like breast cancer: review , 2009, Pathology.

[94]  Lester L. Peters,et al.  Genome-wide association study identifies novel breast cancer susceptibility loci , 2007, Nature.

[95]  L. Bégin,et al.  Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. , 2004, Journal of the National Cancer Institute.

[96]  S. Schnitt,et al.  Ductal carcinoma in situ with basal-like phenotype: a possible precursor to invasive basal-like breast cancer , 2006, Modern Pathology.

[97]  M. J. van de Vijver,et al.  Molecular subtypes of breast cancer and amplification of topoisomerase IIα: predictive role in dose intensive adjuvant chemotherapy , 2006, British Journal of Cancer.

[98]  J. Kładny,et al.  Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients , 2009, Breast Cancer Research and Treatment.

[99]  F. Bertucci,et al.  Gene expression profiling of cancer by use of DNA arrays: how far from the clinic? , 2001, The Lancet. Oncology.

[100]  Hongjuan Zhao,et al.  TP53 mutation status and gene expression profiles are powerful prognostic markers of breast cancer , 2007, Breast Cancer Research.

[101]  A. Nobel,et al.  Concordance among Gene-Expression – Based Predictors for Breast Cancer , 2011 .

[102]  F. Bertucci,et al.  Peritumoural vascular invasion: a major determinant of triple-negative breast cancer outcome. , 2011, European journal of cancer.

[103]  J. Lubiński,et al.  Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[104]  L. Bégin,et al.  Placental Cadherin and the Basal Epithelial Phenotype of BRCA1-Related Breast Cancer , 2005, Clinical Cancer Research.

[105]  J. Dering,et al.  Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/“triple-negative” breast cancer cell lines growing in vitro , 2007, Breast Cancer Research and Treatment.

[106]  I. Ellis,et al.  The influence of basal phenotype on the metastatic pattern of breast cancer. , 2008, Clinical oncology (Royal College of Radiologists (Great Britain)).

[107]  M. J. van de Vijver,et al.  Classification of ductal carcinoma in situ by gene expression profiling , 2006, Breast Cancer Research.

[108]  C. Denkert,et al.  Effect of neoadjuvant anthracycline–taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study , 2010, Breast Cancer Research and Treatment.

[109]  Ajay N. Jain,et al.  Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. , 2006, Cancer cell.

[110]  D. Birnbaum,et al.  Typical medullary breast carcinomas have a basal/myoepithelial phenotype , 2005, The Journal of pathology.

[111]  X. Chen,et al.  Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. , 2011, The Journal of clinical investigation.

[112]  M. Nakano,et al.  Clinical significance of basal-like subtype in triple-negative breast cancer , 2009, Breast cancer.

[113]  S. Cole,et al.  Intrinsic Breast Tumor Subtypes, Race, and Long-Term Survival in the Carolina Breast Cancer Study , 2010, Clinical Cancer Research.

[114]  F. Vicini,et al.  Molecular classification system identifies invasive breast carcinoma patients who are most likely and those who are least likely to achieve a complete pathologic response after neoadjuvant chemotherapy , 2007, Cancer.

[115]  F. Bertucci,et al.  Kinome expression profiling and prognosis of basal breast cancers , 2011, Molecular Cancer.

[116]  John Quackenbush,et al.  Identification of Novel Kinase Targets for the Treatment of Estrogen Receptor–Negative Breast Cancer , 2009, Clinical Cancer Research.

[117]  A. Ashworth,et al.  BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. , 2010, Cell stem cell.

[118]  E. Winer,et al.  Neoadjuvant cisplatin and bevacizumab in triple negative breast cancer (TNBC): Safety and efficacy. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[119]  H. Lane,et al.  The mTOR Inhibitor RAD001 Sensitizes Tumor Cells to DNA-Damaged Induced Apoptosis through Inhibition of p21 Translation , 2005, Cell.

[120]  G. Dontu,et al.  Breast cancer, stem/progenitor cells and the estrogen receptor , 2004, Trends in Endocrinology & Metabolism.

[121]  K. Hess,et al.  Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[122]  R. Cress,et al.  Descriptive analysis of estrogen receptor (ER)‐negative, progesterone receptor (PR)‐negative, and HER2‐negative invasive breast cancer, the so‐called triple‐negative phenotype , 2007, Cancer.

[123]  B. Gusterson.  Do 'basal-like' breast cancers really exist? , 2009, Nature Reviews Cancer.

[124]  B. Lloveras,et al.  HER-2/neu status and response to CMF: retrospective study in a series of operable breast cancer treated with primary CMF chemotherapy , 2007, Journal of Cancer Research and Clinical Oncology.

[125]  J. Rice,et al.  Aberrant methylation of the BRCA1 CpG island promoter is associated with decreased BRCA1 mRNA in sporadic breast cancer cells , 1998, Oncogene.

[126]  M. Keshtgar,et al.  31st annual san antonio breast cancer symposium , 2009 .

[127]  I. Ellis,et al.  An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer , 2007, Genome Biology.

[128]  Robert Tibshirani,et al.  Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene‐expression subtypes of breast cancer , 2006, Genes, chromosomes & cancer.

[129]  Mark Yoffe,et al.  Iniparib plus chemotherapy in metastatic triple-negative breast cancer. , 2011, The New England journal of medicine.

[130]  J. Robertson,et al.  Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation , 2006, The Journal of pathology.

[131]  S. O'toole,et al.  Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage invasive breast cancer using a five-biomarker panel. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[132]  P. Bourne,et al.  Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers. , 2006, Annals of clinical and laboratory science.

[133]  Jeffrey M. Rosen,et al.  Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features , 2009, Proceedings of the National Academy of Sciences.

[134]  Fei Huang,et al.  Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib: rationale for patient selection. , 2007, Cancer research.

[135]  J. Weidhaas,et al.  Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[136]  T. Nielsen,et al.  Expression of epidermal growth factor receptor in relation to BRCA1 status, basal-like markers and prognosis in breast cancer , 2008, Journal of Clinical Pathology.

[137]  T. Lash,et al.  Triple-negative breast cancers are increased in black women regardless of age or body mass index , 2009, Breast Cancer Research.

[138]  R. Tibshirani,et al.  Repeated observation of breast tumor subtypes in independent gene expression data sets , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[139]  Arndt Hartmann,et al.  Protein Expression Profiling in High-Risk Breast Cancer Patients Treated with High-Dose or Conventional Dose–Dense Chemotherapy , 2007, Clinical Cancer Research.

[140]  D. Easton,et al.  Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast , 2006, Histopathology.

[141]  Daniel Birnbaum,et al.  A gene expression signature identifies two prognostic subgroups of basal breast cancer , 2011, Breast Cancer Research and Treatment.

[142]  C. Sotiriou,et al.  ZNF703 gene amplification at 8p12 specifies luminal B breast cancer , 2011, EMBO molecular medicine.

[143]  Jorge S. Reis-Filho,et al.  Resistance to therapy caused by intragenic deletion in BRCA2 , 2008, Nature.

[144]  D. Gudbjartsson,et al.  Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor–positive breast cancer , 2007, Nature Genetics.

[145]  Sung-Bae Kim,et al.  Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. , 2006, Human pathology.

[146]  L. Bégin,et al.  The Prognostic Implication of the Basal-Like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) Phenotype of BRCA1-Related Breast Cancer , 2004, Cancer Research.

[147]  P. Fasching,et al.  Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials , 2010, Breast Cancer Research and Treatment.

[148]  S. Merajver,et al.  BRCA1 regulates human mammary stem/progenitor cell fate , 2008, Proceedings of the National Academy of Sciences.

[149]  S. Chanock,et al.  Genetic Susceptibility Loci for Breast Cancer by Estrogen Receptor Status , 2008, Clinical Cancer Research.

[150]  Samuel Leung,et al.  Basal-Like Breast Cancer Defined by Five Biomarkers Has Superior Prognostic Value than Triple-Negative Phenotype , 2008, Clinical Cancer Research.

[151]  A. Ashworth,et al.  Breast cancer molecular profiling with single sample predictors: a retrospective analysis. , 2010, The Lancet. Oncology.

[152]  D. Ross,et al.  Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer , 2005, Breast Cancer Research.

[153]  M. Erdos,et al.  BRCA1 inhibition of estrogen receptor signaling in transfected cells. , 1999, Science.

[154]  A. Mercurio,et al.  Analysis of Integrin β4 Expression in Human Breast Cancer: Association with Basal-like Tumors and Prognostic Significance , 2008, Clinical Cancer Research.

[155]  F. Bertucci,et al.  Gene expression profiling of breast cell lines identifies potential new basal markers , 2006, Oncogene.

[156]  S. Hirohashi,et al.  Large, central acellular zones indicating myoepithelial tumor differentiation in high-grade invasive ductal carcinomas as markers of predisposition to lung and brain metastases. , 2000, The American journal of surgical pathology.

[157]  Zhiyuan Hu,et al.  Classification and risk stratification of invasive breast carcinomas using a real-time quantitative RT-PCR assay , 2006, Breast Cancer Research.

[158]  O. Fadare,et al.  The Phenotypic Spectrum of Basal-like Breast Cancers: A Critical Appraisal , 2007, Advances in anatomic pathology.

[159]  P. Dam,et al.  Identification of cell-of-origin breast tumor subtypes in inflammatory breast cancer by gene expression profiling , 2006, Breast Cancer Research and Treatment.

[160]  H. Lane,et al.  The mTOR Inhibitor RAD 001 Sensitizes Tumor Cells to DNA-Damaged Induced Apoptosis through Inhibition of p 21 Translation , 2005 .

[161]  W. Woodward,et al.  A gene signature in breast cancer. , 2007, The New England journal of medicine.

[162]  P. Hall,et al.  An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[163]  Daniel Birnbaum,et al.  How different are luminal A and basal breast cancers? , 2009, International journal of cancer.

[164]  A. Ashworth,et al.  BRCA1 dysfunction in sporadic basal-like breast cancer , 2007, Oncogene.

[165]  Sridhar Ramaswamy,et al.  Loss of Heterozygosity and Its Correlation with Expression Profiles in Subclasses of Invasive Breast Cancers , 2004, Cancer Research.

[166]  Amy V Kapp,et al.  Discovery and validation of breast cancer subtypes , 2006, BMC Genomics.

[167]  D. Easton,et al.  Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival , 2007, Breast Cancer Research.

[168]  Puay Hoon Tan,et al.  Conservation of Breast Cancer Molecular Subtypes and Transcriptional Patterns of Tumor Progression Across Distinct Ethnic Populations , 2004, Clinical Cancer Research.

[169]  Nicholas J. Wang,et al.  Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. , 2009, Cancer research.

[170]  Charles M Perou,et al.  Molecular stratification of triple-negative breast cancers. , 2010, The oncologist.

[171]  J. Ross,et al.  Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[172]  F. Bertucci,et al.  Gene expression profiling and clinical outcome in breast cancer. , 2006, Omics : a journal of integrative biology.

[173]  E. Perez,et al.  Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. , 2007, The New England journal of medicine.

[174]  I. Ellis,et al.  Caveolin 1 and Caveolin 2 are associated with breast cancer basal-like and triple-negative immunophenotype , 2008, British Journal of Cancer.

[175]  K Miller,et al.  A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[176]  Ian O Ellis,et al.  Basal-like breast cancer: a critical review. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[177]  Daniel Birnbaum,et al.  Gene expression profiling identifies molecular subtypes of inflammatory breast cancer. , 2005, Cancer research.

[178]  F. Schmitt,et al.  P-cadherin and cytokeratin 5: useful adjunct markers to distinguish basal-like ductal carcinomas in situ , 2006, Virchows Archiv.

[179]  S. Fox,et al.  Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers , 2009, Nature Medicine.