Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment

Garrido-Castro, Ana C.; Lin, Nancy U.; Polyak, Kornelia

doi:10.1158/2159-8290.cd-18-1177

Cited by 1,451Breast Cancer Treatment StudiesBreast Lesions and CarcinomasBRCA gene mutations in cancer

Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment

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Garrido-Castro, Ana C., Lin, Nancy U., Polyak, Kornelia·2019·Cancer Discovery

DOI 10.1158/2159-8290.cd-18-1177PMC PMC6387871

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Abstract

Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype to treat. To date, therapies directed to specific molecular targets have rarely achieved clinically meaningful improvements in outcomes of patients with TNBC, and chemotherapy remains the standard of care. Here, we seek to review the most recent efforts to classify TNBC based on the comprehensive profiling of tumors for cellular composition and molecular features. Technologic advances allow for tumor characterization at ever-increasing depth, generating data that, if integrated with clinical–pathologic features, may help improve risk stratification of patients, guide treatment decisions and surveillance, and help identify new targets for drug development. Significance: TNBC is characterized by higher rates of relapse, greater metastatic potential, and shorter overall survival compared with other major breast cancer subtypes. The identification of biomarkers that can help guide treatment decisions in TNBC remains a clinically unmet need. Understanding the mechanisms that drive resistance is key to the design of novel therapeutic strategies to help prevent the development of metastatic disease and, ultimately, to improve survival in this patient population.

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People with chronic diseases, including cancer, have a negative view of emotions and do not accept their existence.
“People with chronic diseases, including cancer, have a negative view of emotions and do not accept their existence.”
From Effectiveness of Mindfulness Training in Emotion Regulation and Distress Tolerance among Breast Cancer Patients (2024) · cites this paper as [6]
The Introduction discusses triple-negative breast cancer and its clinical outcomes, not patients’ views of emotions. Searches for emotional acceptance, denial, and chronic disease found no passage addressing the claim in our copy. (LLM, conf=0.76)
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One of the important goals of mindfulness is to face negative emotions instead of avoiding them in distress situations by using meditation techniques, such as breathing awareness and increasing awareness of the situation, which help people endure physical and emotional pain.
“one of the important goals of mindfulness is to face negative emotions instead of avoiding them in distress situations by using meditation techniques, such as breathing awareness and increasing awareness of the situation in order to cope and survive in times of crisis, which help people to endure physical and emotional pain. (6)”
From Effectiveness of Mindfulness Training in Emotion Regulation and Distress Tolerance among Breast Cancer Patients (2024) · cites this paper as [6]
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A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds
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Phase III, Double-Blind, Randomized Study Comparing Lapatinib Plus Paclitaxel With Placebo Plus Paclitaxel As First-Line Treatment for Metastatic Breast Cancer
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Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer
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MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition
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PIK3CA mutations in androgen receptor-positive triple negative breast cancer confer sensitivity to the combination of PI3K and androgen receptor inhibitors
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Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer
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Estrogen receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1% to 10% ER-positive by immunohistochemistry
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Inositol polyphosphate 4-phosphatase II regulates PI3K/Akt signaling and is lost in human basal-like breast cancers
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A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1)
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Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity
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The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin
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Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients
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Single-Cell Dynamics Determines Response to CDK4/6 Inhibition in Triple-Negative Breast Cancer
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Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer
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JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade: A Rationale for Cotargeting These Pathways in Metastatic Breast Cancer
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Kinase and BET Inhibitors Together Clamp Inhibition of PI3K Signaling and Overcome Resistance to Therapy
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Receptor conversion in distant breast cancer metastases
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Prevalence of BRCA mutations in an unselected population of triple‐negative breast cancer
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Mechanisms of Therapy Resistance in Patient-Derived Xenograft Models of BRCA1-Deficient Breast Cancer
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Checkpoint inhibitors in triple‐negative breast cancer (TNBC): Where to go from here
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The role of human epidermal growth factor receptor 2 in the survival of women with estrogen and progesterone receptor‐negative, invasive breast cancer: The California Cancer Registry, 1999–2004
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Molecular Stratification of Triple-Negative Breast Cancers
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Targeted Degradation of BET Proteins in Triple-Negative Breast Cancer
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Discordance in receptor status between primary and recurrent breast cancer has a prognostic impact: a single-Institution analysis
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PAM50 assay and the three-gene model for identifying the major and clinically relevant molecular subtypes of breast cancer
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EMERGE: A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Advanced Glycoprotein NMB–Expressing Breast Cancer
Yardley, D. A., Weaver, R., Melisko, M., Saleh, M. N., Arena, F. P., Forero, A., Cigler, T., Stopeck, A., Citrin, D. L., Oliff, I. A., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.56.2959 · Cited by 190 · see citing works
Targeting the PI3K/AKT/mTOR Pathway for the Treatment of Mesenchymal Triple-Negative Breast Cancer
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Homologous Recombination Deficiency and Platinum-Based Therapy Outcomes in Advanced Breast Cancer
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A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2– advanced breast cancer (BELLE-4)
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Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer
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Gene expression profiling of primary breast carcinomas using arrays of candidate genes
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Estrogen Receptor, Progesterone Receptor, Human Epidermal Growth Factor Receptor 2 (HER2), and Epidermal Growth Factor Receptor Expression and Benefit From Lapatinib in a Randomized Trial of Paclitaxel With Lapatinib or Placebo As First-Line Treatment in HER2-Negative or Unknown Metastatic Breast Cancer
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Combination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study
Connolly, R. M., Li, H., Jankowitz, R. C., Zhang, Z., Rudek, M. A., Jeter, S. C., Slater, S. A., Powers, P., Wolff, A. C., Fetting, J. H., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1729 · Cited by 163 · see citing works
PEST Domain Mutations in Notch Receptors Comprise an Oncogenic Driver Segment in Triple-Negative Breast Cancer Sensitive to a γ-Secretase Inhibitor
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Phase II study of ruxolitinib, a selective JAK1/2 inhibitor, in patients with metastatic triple-negative breast cancer
Stover, D. G., del Alcazar, C. R. G., Brock, J. E., Guo, H., Overmoyer, B. A., Balko, J. M., Xu, Q., Bardia, A., Tolaney, S. M., Gelman, R. S., et al. (2018) · npj Breast Cancer · doi:10.1038/s41523-018-0060-z · Cited by 146 · see citing works
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A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67
Jovanović, B., Mayer, I. A., Mayer, E. L., Abramson, V. G., Bardia, A., Sanders, M. E., Kuba, M. G., Estrada, M. V., Beeler, J. S., Shaver, T. M., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-3055 · Cited by 145 · see citing works
Synthetic Lethality of PARP Inhibitors in Combination with MYC Blockade Is Independent of BRCA Status in Triple-Negative Breast Cancer
Carey, J. P. W., Karakaş, C., Bui, T. N., Chen, X., Vijayaraghavan, S., Zhao, Y., Wang, J., Mikule, K. W., Litton, J. K., Hunt, K. K., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1494 · Cited by 145 · see citing works
TOPACIO/Keynote-162 (NCT02657889): A phase 1/2 study of niraparib + pembrolizumab in patients (pts) with advanced triple-negative breast cancer or recurrent ovarian cancer (ROC)—Results from ROC cohort.
Konstantinopoulos, P. A., Waggoner, S. E., Vidal, G. A., Mita, M. M., Fleming, G. F., Holloway, R. W., Le, L. V., Sachdev, J. C., Chapman‐Davis, E., Colón‐Otero, G., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.15_suppl.106 · Cited by 143 · see citing works
Specific inhibition of Notch1 signaling enhances the antitumor efficacy of chemotherapy in triple negative breast cancer through reduction of cancer stem cells
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Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence
Balko, J. M., Schwarz, L. J., Luo, N., Estrada, M. V., Giltnane, J. M., Dávila‐González, D., Wang, K., Sanchez, V. M., Dean, P. T., Combs, S. E., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad3001 · Cited by 137 · see citing works
BRCA1 and HSP90 cooperate in homologous and non-homologous DNA double-strand-break repair and G2/M checkpoint activation
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Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer
Barrett, M. T., Anderson, K. S., Lenkiewicz, E., Andreozzi, M., Cunliffe, H. E., Klassen, C. L., Dueck, A. C., McCullough, A. E., Reddy, S., Ramanathan, R. K., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4494 · Cited by 134 · see citing works
Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A.
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The human c-Kirstenrasgene is activated by a novel mutation in codon 13 in the breast carcinoma cell line MDA-MB231
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Phase Ib trial of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC).
Adams, S., Diamond, J. R., Hamilton, E. P., Pohlmann, P. R., Tolaney, S. M., Molinero, L. L., He, X., Waterkamp, D., Funke, R. P., & Powderly, J. D. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.1009 · Cited by 127 · see citing works
Pathological Response in a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification
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WSG ADAPT – adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early breast cancer: study protocol for a prospective, multi-center, controlled, non-blinded, randomized, investigator initiated phase II/III trial
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Abstract 2986: Atezolizumab in metastatic TNBC (mTNBC): Long-term clinical outcomes and biomarker analyses
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Genetic alterations of triple negative breast cancer by targeted next-generation sequencing and correlation with tumor morphology
Weisman, P. S., Ng, C. K. Y., Brogi, E., Eisenberg, R. E. K., Won, H. H., Piscuoglio, S., Filippo, M. R. D., Ioris, R. A., Akram, M. M., Norton, L., et al. (2016) · Modern Pathology · doi:10.1038/modpathol.2016.39 · Cited by 114 · see citing works
Predicting response and survival in chemotherapy-treated triple-negative breast cancer
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TGFβ induces the formation of tumour-initiating cells in claudinlow breast cancer
Bruna, A., Greenwood, W., Quesne, J. P. C. L., Teschendorff, A. E., Miranda‐Saavedra, D., Rueda, O. M., Sandoval, J. L., Vidaković, A. T., Saadi, A., Pharoah, P. D. P., et al. (2012) · Nature Communications · doi:10.1038/ncomms2039 · Cited by 109 · see citing works
RING domain–deficient BRCA1 promotes PARP inhibitor and platinum resistance
Wang, Y., Krais, J. J., Bernhardy, A. J., Nicolas, É., Cai, K. Q., Harrell, M. I., Kim, H. H., George, E. M., Swisher, E. M., Simpkins, F. A., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci87033 · Cited by 107 · see citing works
Predictive Biomarker Profiling of > 6000 Breast Cancer Patients Shows Heterogeneity in TNBC, With Treatment Implications
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Epigenetic Regulation of Cancer Stem Cell Genes in Triple-Negative Breast Cancer
Kagara, N., Huynh, K. T., Kuo, C. T., Okano, H., Sim, M., Elashoff, D. A., Chong, K. K., Giuliano, A. E., & Hoon, D. S. �. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.03.019 · Cited by 96 · see citing works
Tumor Evolution in Two Patients with Basal-like Breast Cancer: A Retrospective Genomics Study of Multiple Metastases
Hoadley, K. A., Siegel, M. B., Kanchi, K., Miller, C. A., Ding, L., Wei, Z., He, X., Parker, J. S., Wendl, M. C., Fulton, R. S., et al. (2016) · PLoS Medicine · doi:10.1371/journal.pmed.1002174 · Cited by 95 · see citing works
Synergistic Effect of the γ-Secretase Inhibitor PF-03084014 and Docetaxel in Breast Cancer Models
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Borderline ER-positive primary breast cancer gains no significant survival benefit from endocrine therapy: a systematic review and meta-analysis
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The Biological Functions of the Versatile Transcription Factors STAT3 and STAT5 and New Strategies for their Targeted Inhibition
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Phase I study of the gamma secretase inhibitor PF-03084014 in combination with docetaxel in patients with advanced triple-negative breast cancer
Locatelli, M., Aftimos, P. G., Dees, E. C., LoRusso, P. M., Pegram, M. D., Awada, A. H., Huang, B., Cesari, R., Jiang, Y., Shaik, M. N., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.13727 · Cited by 91 · see citing works
Abstract GS1-04: IMpassion130: Efficacy in immune biomarker subgroups from the global, randomized, double-blind, placebo-controlled, phase III study of atezolizumab + nab-paclitaxel in patients with treatment-naïve, locally advanced or metastatic triple-negative breast cancer
Emens, L., Loi, S., Rugo, H. S., Schneeweiß, A., Dieras, V. C., Iwata, H., Barrios, C., Nechaeva, M. N., Molinero, L. L., Duc, A. N., et al. (2019) · Cancer Research · doi:10.1158/1538-7445.sabcs18-gs1-04 · Cited by 81 · see citing works
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Authors: Garrido-Castro, A. C., Lin, N. U., & Polyak, K.
Affiliations: Harvard University (US)
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
ORCID: Garrido-Castro, Ana C.
Venue: Cancer Discovery
Publisher: American Association for Cancer Research (AACR)
Published: 2019-02-01
Volume: 9
Issue: 2
Pages: 176-198
ISSN: 2159-8274 (ISSN-L)
2159-8290
DOI: 10.1158/2159-8290.cd-18-1177
PMC: PMC6387871
OpenAlex: W2911718257
Cited by: 1,451
References: 159
Citations by year: 2026: 180 · 2025: 221 · 2024: 237 · 2023: 242 · 2022: 228 · 2021: 182 · 2020: 121 · 2019: 40
FWCI: 13.64
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Cancer Discovery (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: NCI (R35CA197623)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Keywords: triple-negative breast cancer, molecular classification, tumor profiling, biomarkers, risk stratification, treatment selection, chemotherapy, drug resistance mechanisms, metastasis, patient selection
MeSH terms: Female, Humans, Prognosis, Biomarkers, Tumor, Patient Selection, Gene Expression Profiling, Molecular Targeted Therapy, Triple Negative Breast Neoplasms

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Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment

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