Recent advances in breast cancer research impacting clinical diagnostic practice

During the last decade, the genomics revolution has driven critical advances in molecular oncology and pathology, and a deeper appreciation of heterogeneity that is beginning to reshape our thinking around diagnostic classification. Recent developments have seen existing classification systems modified and improved where possible, gene‐based diagnostics implemented and tumour–immune interactions modulated. We present a detailed discussion of this progress, including advances in the understanding of breast tumour classification, e.g. mixed ductal–lobular tumours and the spectrum of triple‐negative breast cancer. The latest information on clinical trials and the implementation of gene‐based diagnostics, including MammaPrint and Oncotype Dx and others, is synthesised, and emerging targeted therapies, as well as the burgeoning immuno‐oncology field, and their relevance in breast cancer, are discussed. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[1]  S. Adams Dramatic response of metaplastic breast cancer to chemo-immunotherapy , 2017, npj Breast Cancer.

[2]  C. Isaacs,et al.  Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. , 2014, The Lancet. Oncology.

[3]  Jamie R. Kutasovic,et al.  Mixed ductal‐lobular carcinomas: evidence for progression from ductal to lobular morphology , 2018, The Journal of pathology.

[4]  E. Alli,et al.  Synergistic chemosensitivity of triple-negative breast cancer cell lines to poly(ADP-Ribose) polymerase inhibition, gemcitabine, and cisplatin. , 2010, Cancer research.

[5]  David T. W. Jones,et al.  Signatures of mutational processes in human cancer , 2013, Nature.

[6]  I. Ellis,et al.  Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family , 2016, Modern Pathology.

[7]  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.

[8]  C. Bakal,et al.  Single-Cell Dynamics Determines Response to CDK4/6 Inhibition in Triple-Negative Breast Cancer , 2017, Clinical Cancer Research.

[9]  K. Okkenhaug,et al.  Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy. , 2016, Cancer discovery.

[10]  S Michiels,et al.  Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[11]  Jack Cuzick,et al.  Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  Sunil R. Lakhani,et al.  WHO classification of tumours of the breast , 2012 .

[13]  J. Tchou,et al.  Is Age Trumping Genetic Profiling in Clinical Practice? Relationship of Chemotherapy Recommendation and Oncotype DX Recurrence Score in Patients Aged < 50 Years versus ≥ 50 Years, and Trends Over Time , 2018, Annals of Surgical Oncology.

[14]  A. Buzdar,et al.  Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  R. Greil,et al.  A New Molecular Predictor of Distant Recurrence in ER-Positive, HER2-Negative Breast Cancer Adds Independent Information to Conventional Clinical Risk Factors , 2011, Clinical Cancer Research.

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

[17]  Virginia G Kaklamani,et al.  Adjuvant Chemotherapy Guided by a 21‐Gene Expression Assay in Breast Cancer , 2018, The New England journal of medicine.

[18]  M. Dowsett,et al.  Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  Steven J. M. Jones,et al.  Comprehensive molecular portraits of human breast tumours , 2013 .

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

[21]  Mark T. W. Ebbert,et al.  A Comparison of PAM50 Intrinsic Subtyping with Immunohistochemistry and Clinical Prognostic Factors in Tamoxifen-Treated Estrogen Receptor–Positive Breast Cancer , 2010, Clinical Cancer Research.

[22]  L. V. van't Veer,et al.  Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. , 2006, Journal of the National Cancer Institute.

[23]  A. Børresen-Dale,et al.  Mutational Processes Molding the Genomes of 21 Breast Cancers , 2012, Cell.

[24]  S. Loi,et al.  Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. , 2018, European journal of cancer.

[25]  R. Bast,et al.  Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  M. J. van de Vijver,et al.  Long-term impact of the 70-gene signature on breast cancer outcome , 2014, Breast Cancer Research and Treatment.

[27]  M. Stratton,et al.  Deciphering Signatures of Mutational Processes Operative in Human Cancer , 2013, Cell reports.

[28]  Norikazu Masuda,et al.  Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. , 2017, The Lancet. Oncology.

[29]  C. Maher,et al.  Genomic and transcriptomic heterogeneity in metaplastic carcinomas of the breast , 2017, npj Breast Cancer.

[30]  A. Cimino-Mathews,et al.  Whole-Exome Sequencing of Metaplastic Breast Carcinoma Indicates Monoclonality with Associated Ductal Carcinoma Component , 2017, Clinical Cancer Research.

[31]  R. Greil,et al.  EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2-negative early breast cancer , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[32]  Woo Yong Lee,et al.  Prevalence and detection of low-allele-fraction variants in clinical cancer samples , 2017, Nature Communications.

[33]  Yudong D. He,et al.  A Gene-Expression Signature as a Predictor of Survival in Breast Cancer , 2002 .

[34]  P. Lønning,et al.  Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial. , 2018, The Lancet. Oncology.

[35]  J. Crown,et al.  Trastuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in HER-2-non-amplified breast cancer cell lines. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[36]  Steven J. M. Jones,et al.  Comprehensive molecular portraits of human breast tumors , 2012, Nature.

[37]  E. Winer,et al.  Overcoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors. , 2016, Cancer cell.

[38]  H. Mouridsen Letrozole in advanced breast cancer: the PO25 trial , 2007, Breast Cancer Research and Treatment.

[39]  William Audeh,et al.  Association of 70-Gene Signature Assay Findings With Physicians’ Treatment Guidance for Patients With Early Breast Cancer Classified as Intermediate Risk by the 21-Gene Assay , 2018, JAMA oncology.

[40]  C. Sautès-Fridman,et al.  The immune contexture in human tumours: impact on clinical outcome , 2012, Nature Reviews Cancer.

[41]  F. Marincola,et al.  Pan-cancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from The Cancer Genome Atlas (TCGA) , 2018, Journal of Immunotherapy for Cancer.

[42]  E. Yang,et al.  Poly(ADP-ribose) polymerase activity and inhibition in cancer. , 2017, Seminars in cell & developmental biology.

[43]  T. Nielsen,et al.  The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[44]  A. Børresen-Dale,et al.  The landscape of cancer genes and mutational processes in breast cancer , 2012, Nature.

[45]  O. Mariani,et al.  The Landscape of Somatic Genetic Alterations in Metaplastic Breast Carcinomas , 2017, Clinical Cancer Research.

[46]  J. Gartner,et al.  Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer , 2018, Nature Medicine.

[47]  John M S Bartlett,et al.  OPTIMA prelim: a randomised feasibility study of personalised care in the treatment of women with early breast cancer. , 2016, Health technology assessment.

[48]  L. Bracci,et al.  Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer , 2013, Cell Death and Differentiation.

[49]  R. Greil,et al.  Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[50]  B. Fox,et al.  Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40 , 2017, Clinical Cancer Research.

[51]  Gary D Bader,et al.  Association analysis identifies 65 new breast cancer risk loci , 2017, Nature.

[52]  S. Chandarlapaty,et al.  A phase II open-label study of ganetespib, a novel heat shock protein 90 inhibitor for patients with metastatic breast cancer. , 2014, Clinical breast cancer.

[53]  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.

[54]  E. Birney,et al.  HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures , 2017, Nature Medicine.

[55]  F. Bertucci,et al.  Immunotherapy in Breast Cancer: the Emerging Role of PD-1 and PD-L1 , 2017, Current Oncology Reports.

[56]  E. Knudsen,et al.  CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models , 2014, Genes & cancer.

[57]  A. Hida,et al.  Prognostic and predictive impacts of tumor-infiltrating lymphocytes differ between Triple-negative and HER2-positive breast cancers treated with standard systemic therapies , 2016, Breast Cancer Research and Treatment.

[58]  David C. Jones,et al.  Landscape of somatic mutations in 560 breast cancer whole genome sequences , 2016, Nature.

[59]  J. Griggs,et al.  American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[60]  J. Cuzick,et al.  Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[61]  E. Winer,et al.  Atezolizumab and Nab‐Paclitaxel in Advanced Triple‐Negative Breast Cancer , 2018, The New England journal of medicine.

[62]  L. Jones,et al.  Mechanisms of immune evasion in breast cancer , 2018, BMC Cancer.

[63]  S. Loi,et al.  Combined CDK4/6 and PI3Kα Inhibition Is Synergistic and Immunogenic in Triple-Negative Breast Cancer. , 2017, Cancer research.

[64]  Jamie R. Kutasovic,et al.  Phenotypic and molecular dissection of metaplastic breast cancer and the prognostic implications , 2018, The Journal of pathology.

[65]  Jack Cuzick,et al.  Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population. , 2013, The Lancet. Oncology.

[66]  Hui Yang,et al.  IDH1 and IDH2 Mutations in Tumorigenesis: Mechanistic Insights and Clinical Perspectives , 2012, Clinical Cancer Research.

[67]  S. Loi,et al.  Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer , 2018, The New England journal of medicine.

[68]  Yi Zhang,et al.  Breast Cancer Index Identifies Early-Stage Estrogen Receptor–Positive Breast Cancer Patients at Risk for Early- and Late-Distant Recurrence , 2013, Clinical Cancer Research.

[69]  Ekta Khurana,et al.  MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB–NFIB fusion gene , 2018, The Journal of pathology.

[70]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[71]  J. Pearson,et al.  Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance , 2015, The Journal of pathology.

[72]  J. Joo,et al.  Prognostic Implications of Tumor-Infiltrating Lymphocytes in Association With Programmed Death Ligand 1 Expression in Early-Stage Breast Cancer. , 2016, Clinical breast cancer.

[73]  A. Vincent-Salomon,et al.  ERBB2 mutations associated with solid variant of high-grade invasive lobular breast carcinomas , 2016, Oncotarget.

[74]  C. Denkert,et al.  Risk Assessment after Neoadjuvant Chemotherapy in Luminal Breast Cancer Using a Clinicomolecular Predictor , 2018, Clinical Cancer Research.

[75]  S. Loi,et al.  Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. , 2016, The Lancet Oncology.

[76]  G. Hortobagyi,et al.  Prevalence of ESR1 Mutations in Cell-Free DNA and Outcomes in Metastatic Breast Cancer: A Secondary Analysis of the BOLERO-2 Clinical Trial. , 2016, JAMA oncology.

[77]  F M Blows,et al.  Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[78]  F. Guadagni,et al.  Effects of conventional therapeutic interventions on the number and function of regulatory T cells , 2013, Oncoimmunology.

[79]  I. Ellis,et al.  Heterogeneity of tumour‐infiltrating lymphocytes in breast cancer and its prognostic significance , 2018, Histopathology.

[80]  K. Loh,et al.  Targeted agents for HER2-positive breast cancer in older adults: current and future perspectives , 2018, Expert opinion on investigational drugs.

[81]  P. Campbell,et al.  Genomic Characterization of Primary Invasive Lobular Breast Cancer. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[82]  M. Piccart,et al.  Treatment of advanced HER2-positive breast cancer: 2018 and beyond. , 2018, Cancer treatment reviews.

[83]  G. MacGrogan,et al.  Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: a comparative study of 9 additional cases , 2018, Modern Pathology.

[84]  Alison Stopeck,et al.  HSP90 Inhibition Is Effective in Breast Cancer: A Phase II Trial of Tanespimycin (17-AAG) Plus Trastuzumab in Patients with HER2-Positive Metastatic Breast Cancer Progressing on Trastuzumab , 2011, Clinical Cancer Research.

[85]  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.

[86]  Lajos Pusztai,et al.  Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[87]  Aleix Prat Aparicio Comprehensive molecular portraits of human breast tumours , 2012 .

[88]  Stefan Michiels,et al.  Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[89]  Fang Yang,et al.  Potential biomarkers of CDK4/6 inhibitors in hormone receptor-positive advanced breast cancer , 2018, Breast Cancer Research and Treatment.

[90]  C. Isaacs,et al.  Molecular Alterations and Everolimus Efficacy in Human Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Breast Cancers: Combined Exploratory Biomarker Analysis From BOLERO-1 and BOLERO-3. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[91]  S. Chia,et al.  Novel agents and associated toxicities of inhibitors of the pi3k/Akt/mtor pathway for the treatment of breast cancer. , 2015, Current oncology.

[92]  Steven J. M. Jones,et al.  Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer , 2015, Cell.

[93]  E. Winer,et al.  Cabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study , 2016, Breast Cancer Research and Treatment.

[94]  Janice S. Sung,et al.  A Pilot Study of Preoperative Single-Dose Ipilimumab and/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling , 2016, Clinical Cancer Research.

[95]  R. Greil,et al.  The PAM50 Risk-of-Recurrence Score Predicts Risk for Late Distant Recurrence after Endocrine Therapy in Postmenopausal Women with Endocrine-Responsive Early Breast Cancer , 2014, Clinical Cancer Research.

[96]  Xian Chen,et al.  Synthetic Lethality of PARP Inhibitors in Combination with MYC Blockade Is Independent of BRCA Status in Triple-Negative Breast Cancer. , 2018, Cancer research.

[97]  M. Cronin,et al.  Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[98]  J. Isola,et al.  Trastuzumab causes antibody-dependent cellular cytotoxicity–mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance , 2007, Molecular Cancer Therapeutics.

[99]  A. Berjón,et al.  Comparison of risk classification between EndoPredict and MammaPrint in ER-positive/HER2-negative primary invasive breast cancer , 2017, PloS one.

[100]  L. V. van't Veer,et al.  70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. , 2016, The New England journal of medicine.

[101]  L. Voorwerk,et al.  Towards predictive biomarkers for immunotherapy response in breast cancer patients , 2018 .

[102]  Joyce Lee,et al.  PI3K/Akt/mTOR inhibitors in breast cancer , 2015, Cancer biology & medicine.

[103]  M. Piccart,et al.  Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. , 2012, The New England journal of medicine.

[104]  I. Jatoi,et al.  Hypothesis: can the abscopal effect explain the impact of adjuvant radiotherapy on breast cancer mortality? , 2018, npj Breast Cancer.

[105]  A. Melcher,et al.  The immunological consequences of radiation‐induced DNA damage , 2019, The Journal of pathology.

[106]  Virginia G Kaklamani,et al.  Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. , 2015, The New England journal of medicine.

[107]  J. Reis-Filho,et al.  Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants , 2016, npj Breast Cancer.

[108]  A. Børresen-Dale,et al.  The Life History of 21 Breast Cancers , 2012, Cell.

[109]  G. Hortobagyi,et al.  PARP Inhibitor Upregulates PD-L1 Expression and Enhances Cancer-Associated Immunosuppression , 2017, Clinical Cancer Research.

[110]  Steven A. Roberts,et al.  An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers , 2013, Nature Genetics.

[111]  M. Goetz,et al.  MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[112]  I. Ellis,et al.  Histological features of medullary carcinoma and prognosis in triple-negative basal-like carcinomas of the breast , 2010, Modern Pathology.

[113]  D. Petrylak,et al.  Augmented HER-2–Specific Immunity during Treatment with Trastuzumab and Chemotherapy , 2007, Clinical Cancer Research.

[114]  J. Cortés,et al.  Targeting FGFR pathway in breast cancer. , 2018, Breast.

[115]  J. Cuzick,et al.  Comparison of EndoPredict and EPclin With Oncotype DX Recurrence Score for Prediction of Risk of Distant Recurrence After Endocrine Therapy , 2016, Journal of the National Cancer Institute.

[116]  Benjamin J. Raphael,et al.  Mutational landscape and significance across 12 major cancer types , 2013, Nature.

[117]  M. Goetz,et al.  Abemaciclib as initial therapy for advanced breast cancer: MONARCH 3 updated results in prognostic subgroups , 2021, NPJ breast cancer.

[118]  Qihua Tan,et al.  Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles , 2018, Modern Pathology.

[119]  I. Ellis,et al.  Microglandular adenosis associated with triple‐negative breast cancer is a neoplastic lesion of triple‐negative phenotype harbouring TP53 somatic mutations , 2016, The Journal of pathology.

[120]  J. Cuzick,et al.  Comparison of the Performance of 6 Prognostic Signatures for Estrogen Receptor–Positive Breast Cancer , 2018, JAMA oncology.

[121]  J. Dering,et al.  PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro , 2009, Breast Cancer Research.

[122]  S. Ferree,et al.  Prediction of Response to Neoadjuvant Chemotherapy Using Core Needle Biopsy Samples with the Prosigna Assay , 2015, Clinical Cancer Research.

[123]  A. Howell,et al.  Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[124]  Jack Cuzick,et al.  Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[125]  M. Piccart,et al.  Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

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

[127]  S. Domchek,et al.  Immunotherapy for Breast Cancer: What Are We Missing? , 2017, Clinical Cancer Research.

[128]  S. Hoover,et al.  Histologic heterogeneity of triple negative breast cancer: A National Cancer Centre Database analysis. , 2018, European journal of cancer.

[129]  M. Hao,et al.  Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer. , 2018, Cancer discovery.

[130]  Xin Huang,et al.  The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. , 2015, The Lancet. Oncology.

[131]  Julie M. Batten,et al.  IDH2 Mutations Define a Unique Subtype of Breast Cancer with Altered Nuclear Polarity. , 2016, Cancer research.

[132]  S. Fox,et al.  Tumour-infiltrating lymphocytes and the emerging role of immunotherapy in breast cancer. , 2017, Pathology.

[133]  Erica K. Barnell,et al.  A Phase II Trial of Neoadjuvant MK-2206, an AKT Inhibitor, with Anastrozole in Clinical Stage II or III PIK3CA-Mutant ER-Positive and HER2-Negative Breast Cancer , 2017, Clinical Cancer Research.

[134]  E. Winer,et al.  Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. , 2016, The New England journal of medicine.