Update on triple‐negative breast cancers – highlighting subtyping update and treatment implication

Abstract

Triple‐negative breast cancer (TNBC) remains a major challenge in breast cancer management. Continuing research in the past years aimed at understanding the biology of this tumour and developing more effective therapeutic options. It is now clear that TNBC is vastly heterogeneous with diverse histological, molecular, immunological profiles and clinical differences. Current evidence suggested the existence of at least four predominant subtypes based on expression profiling across studies. These subtypes exhibited specific genomic alterations and tumour microenvironment. Subtype‐specific therapeutic strategies were identified. Recognising these subtypes allows not only an improved prognostication but also a better treatment decision. Herein, we provide an overview of the recent findings on TNBC heterogeneity at different levels and corresponding subtyping. The characteristic of subtypes and the implication of these subtypings in therapeutic approaches are also discussed.

Automated image quantification of immunohistochemistry-stained immune cells in triple-negative breast cancer

“…4E). The latter analysis revealed that most markers appeared correlated with regard to cell count levels, de ning at one end an immune cold subset of TNBC tumours and at the other end an immune hot tumour subset, as reported previously (10,12). Consistent with the established prognostic role of immune response in TNBC and the general immune marker-to-marker co-expression in TMA cores, patient strati cation based on automated cell counts subdivided patients in our cohort with adjuvant systemic therapy into groups with differing prognosis in terms of IDFS (Fig.…”

“…Still, within TNBC there is a large heterogeneity in the level of immune response observed across individual tumours (10,11). This immune heterogeneity has also been recognized in proposed transcriptional TNBC subtypes though an immunomodulatory (IM) subtype/phenotype (12). For instance, in 2011 Lehmann et al proposed the IM subtype as one of six intrinsic TNBC subtypes, but later re ned this subtyping scheme to comprise four subtypes (BL1, BL2, M, LAR) where the IM subtype can be superimposed on the former as an independent feature of the tumour (13).…”

Annual Review Issue: Breast Pathology

“…Further subtyping of TNBC may aid subtype‐specific therapeutic strategies. Professor Gary Tse and colleagues 7 share an update on TNBC with highlights on subtyping and treatment (target) implications. Breast tumours with myoepithelial phenotype typically show triple negativity but they exhibit better prognosis and clinical behaviour than other TNBC.…”

Liquid Biopsy in the Management of Breast Cancer Patients: Where Are We Now and Where Are We Going

“…Analysis of the gene expression pattern of BC datasets discovered TNBC cellular heterogeneity grouped under six molecular subtypes: basal-like (BL1 & BL2), mesenchymal, mesenchymal stem-like, luminal androgen receptor subtype, and immunomodulatory [ 32 ]. Chemotherapy remains the standard treatment for patients even if TNBC is divided into six types of tumors.…”