Triple-negative Breast Cancer: Promising Prognostic Biomarkers Currently in Development

Overview

Journal Expert Rev Anticancer Ther

Specialties Oncology
Pharmacology

Date 2020 Nov 17

PMID 33198517

Citations 74

Authors

Jasmine Sukumar

Kelly Gast

Dionisia Quiroga

Maryam Lustberg

Nicole Williams

Affiliations

Soon will be listed here.

Abstract

: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. Validated prognostic and predictive biomarkers are needed to guide treatment decisions and prognostication.: In this review, we discuss established and developing prognostic and predictive biomarkers in TNBC and associated emerging and approved therapies. Biomarkers reviewed include epidermal growth factor receptor (EGFR), vascular endothelial growth factors (VEGF), fibroblast growth factor receptor (FGFR), human epidermal growth factor receptor 2 (HER2), androgen receptor, NOTCH signaling, oxidative stress/redox signaling, microRNAs, mutation, breast cancer susceptibility gene 1 or 2 () mutation/homologous recombination deficiency (HRD), NTRK gene fusion, PI3K/AKT/mTOR, immune biomarkers (programmed death-ligand 1 (PDL1), tumor-infiltrating lymphocytes (TILs), tumor mutational burden (TMB), neoantigens, defects in DNA mismatch repair proteins (dMMR)/microsatellite instability-high (MSI-H)), circulating tumor cells/cell-free DNA, novel targets of antibody-drug conjugates, and residual disease.: Biomarker-driven care in the management of TNBC is increasing and has helped expand options for patients diagnosed with this subtype of breast cancer. Research efforts are ongoing to identify additional biomarkers and targeted treatment options with the ultimate goal of improving clinical outcomes and survivorship.

Citing Articles

Classifications of triple-negative breast cancer: insights and current therapeutic approaches.

Chen Z, Liu Y, Lyu M, Chan C, Sun M, Yang X Cell Biosci. 2025; 15(1):13.

PMID: 39893480 PMC: 11787746. DOI: 10.1186/s13578-025-01359-0.

MRPL24 drives breast cancer metastasis and stemness by targeting c-MYC, BRD4, and STAT3.

Khan A, Khan I, Man S, Liu S, Ailun G, Abbas M 3 Biotech. 2025; 15(2):37.

PMID: 39802327 PMC: 11718041. DOI: 10.1007/s13205-024-04196-z.

Association of Proteasome Activity and Pool Heterogeneity with Markers Determining the Molecular Subtypes of Breast Cancer.

Kondakova I, Sereda E, Sidenko E, Vtorushin S, Vedernikova V, Burov A Cancers (Basel). 2025; 17(1.

PMID: 39796785 PMC: 11720674. DOI: 10.3390/cancers17010159.

Use of Gain-of-Function Screening to Identify miRNAs Involved in Paclitaxel Resistance in Triple-Negative Breast Cancer.

Nemours S, Sole C, Goicoechea I, Armesto M, Arestin M, Urruticoechea A Int J Mol Sci. 2025; 25(24.

PMID: 39769392 PMC: 11728027. DOI: 10.3390/ijms252413630.

Carbonic Anhydrase IX Enzyme in Triple Negative Breast Carcinoma: Relationship With Prognostic Factors and Response to Neoadjuvant Chemotherapy.

Arslan Solmaz O, Kutluer N, Bozan M Eur J Breast Health. 2025; 21(1):57-62.

PMID: 39744916 PMC: 11706115. DOI: 10.4274/ejbh.galenos.2024.2024-6-1.

References

Burstein H, Curigliano G, Loibl S, Dubsky P, Gnant M, Poortmans P . Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019. Ann Oncol. 2019; 30(10):1541-1557. DOI: 10.1093/annonc/mdz235. View

Fehrenbacher L, Cecchini R, Geyer Jr C, Rastogi P, Costantino J, Atkins J . NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+ or 2. J Clin Oncol. 2019; 38(5):444-453. PMC: 7007289. DOI: 10.1200/JCO.19.01455. View

Luen S, Virassamy B, Savas P, Salgado R, Loi S . The genomic landscape of breast cancer and its interaction with host immunity. Breast. 2016; 29:241-50. DOI: 10.1016/j.breast.2016.07.015. View

Garcia J, Hurwitz H, Sandler A, Miles D, Coleman R, Deurloo R . Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook. Cancer Treat Rev. 2020; 86:102017. DOI: 10.1016/j.ctrv.2020.102017. View

Matsuda N, Wang X, Lim B, Krishnamurthy S, Alvarez R, Willey J . Safety and Efficacy of Panitumumab Plus Neoadjuvant Chemotherapy in Patients With Primary HER2-Negative Inflammatory Breast Cancer. JAMA Oncol. 2018; 4(9):1207-1213. PMC: 6143003. DOI: 10.1001/jamaoncol.2018.1436. View

Yang F, Zhang W, Shen Y, Guan X . Identification of dysregulated microRNAs in triple-negative breast cancer (review). Int J Oncol. 2015; 46(3):927-32. DOI: 10.3892/ijo.2015.2821. View

da Silva J, Nunes N, Izetti P, Gomes de Mesquita G, de Melo A . Triple negative breast cancer: A thorough review of biomarkers. Crit Rev Oncol Hematol. 2020; 145:102855. DOI: 10.1016/j.critrevonc.2019.102855. View

Schmid P, Adams S, Rugo H, Schneeweiss A, Barrios C, Iwata H . Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018; 379(22):2108-2121. DOI: 10.1056/NEJMoa1809615. View

Yarchoan M, Johnson 3rd B, Lutz E, Laheru D, Jaffee E . Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer. 2017; 17(4):209-222. PMC: 5575801. DOI: 10.1038/nrc.2016.154. View

10.

Stevic I, Muller V, Weber K, Fasching P, Karn T, Marme F . Specific microRNA signatures in exosomes of triple-negative and HER2-positive breast cancer patients undergoing neoadjuvant therapy within the GeparSixto trial. BMC Med. 2018; 16(1):179. PMC: 6178264. DOI: 10.1186/s12916-018-1163-y. View

11.

Andre F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo H . Alpelisib for -Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019; 380(20):1929-1940. DOI: 10.1056/NEJMoa1813904. View

12.

Lustberg M, Stover D, Chalmers J . Implementing Liquid Biopsies in Clinical Trials: State of Affairs, Opportunities, and Challenges. Cancer J. 2018; 24(2):61-64. PMC: 5880324. DOI: 10.1097/PPO.0000000000000309. View

13.

Carey L, Rugo H, Marcom P, Mayer E, Esteva F, Ma C . TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol. 2012; 30(21):2615-23. PMC: 3413275. DOI: 10.1200/JCO.2010.34.5579. View

14.

Sabatier R, Finetti P, Mamessier E, Adelaide J, Chaffanet M, Ali H . Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget. 2015; 6(7):5449-64. PMC: 4467160. DOI: 10.18632/oncotarget.3216. View

15.

Adams S, Gray R, Demaria S, Goldstein L, Perez E, Shulman L . Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014; 32(27):2959-66. PMC: 4162494. DOI: 10.1200/JCO.2013.55.0491. View

16.

Dawson S, Tsui D, Murtaza M, Biggs H, Rueda O, Chin S . Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013; 368(13):1199-209. DOI: 10.1056/NEJMoa1213261. View

17.

Jiao S, Xia W, Yamaguchi H, Wei Y, Chen M, Hsu J . PARP Inhibitor Upregulates PD-L1 Expression and Enhances Cancer-Associated Immunosuppression. Clin Cancer Res. 2017; 23(14):3711-3720. PMC: 5511572. DOI: 10.1158/1078-0432.CCR-16-3215. View

18.

Wolf D, Yau C, Sanil A, Glas A, Petricoin E, Wulfkuhle J . DNA repair deficiency biomarkers and the 70-gene ultra-high risk signature as predictors of veliparib/carboplatin response in the I-SPY 2 breast cancer trial. NPJ Breast Cancer. 2017; 3:31. PMC: 5572474. DOI: 10.1038/s41523-017-0025-7. View

19.

Kahraman M, Roske A, Laufer T, Fehlmann T, Backes C, Kern F . MicroRNA in diagnosis and therapy monitoring of early-stage triple-negative breast cancer. Sci Rep. 2018; 8(1):11584. PMC: 6072710. DOI: 10.1038/s41598-018-29917-2. View

20.

Desmedt C, Haibe-Kains B, Wirapati P, Buyse M, Larsimont D, Bontempi G . Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res. 2008; 14(16):5158-65. DOI: 10.1158/1078-0432.CCR-07-4756. View