How shall we treat early triple-negative breast cancer (TNBC): from the current standard to upcoming immuno-molecular strategies

Abstract

Triple-negative breast cancer (TNBC) is a long-lasting orphan disease in terms of little therapeutic progress during the past several decades and still the standard of care remains chemotherapy. Experimental discovery of molecular signatures including the ‘BRCAness’ highlighted the innate heterogeneity of TNBC, generating the diversity of TNBC phenotypes. As it contributes to enhancing genomic instability, it has widened the therapeutic spectrum of TNBC. In particular, unusual sensitivity to DNA damaging agents was denoted in patients with BRCA deficiency, suggesting therapeutic benefit from platinum and poly(ADP-ribose) polymerase inhibitors. However, regardless of enriched chemosensitivity and immunogenicity, majority of patients with TNBC still suffer from dismal clinical outcomes including early relapse and metastatic spread. Therefore, efforts into more precise and personalised treatment are critical at this point. Accordingly, the advance of multiomics has revealed novel actionable targets including PI3K-Akt-mTOR and epidermal growth factor receptor signalling pathways, which might actively participate in modulating the chemosensitivity and immune system. Also, TNBC has long been considered a potential protagonist of immunotherapy in breast cancer, supported by abundant tumour-infiltrating lymphocytes and heterogeneous tumour microenvironment. Despite that, earlier studies showed somewhat unsatisfactory results of monotherapy with immune-checkpoint inhibitors, consistently durable responses in responders were noteworthy. Based on these results, further combinatorial trials either with other chemotherapy or targeted agents are underway. Incorporating immune-molecular targets into combination as well as refining the standard chemotherapy might be the key to unlock the future of TNBC. In this review, we share the current and upcoming treatment options of TNBC in the framework of scientific and clinical data, especially focusing on early stage of TNBC.

Ultra-sensitive Nanoprobe Modified with Tumor Cell Membrane for UCL/MRI/PET Multimodality Precise Imaging of Triple-Negative Breast Cancer

“…Four-to six-week-old female BALB/c nude mice (Beijing HuaFuKang Bioscience Co. Ltd, China) were subcutaneously injected with 100 μL serum-free PBS containing 5 × 10 6 MDA-MB-231 cells or MCF-7 cells into the upper limbs or lower limbs of each mouse, according to the imaging situation. About 1 week after the injection, when the tumor volume reached 60-250 mm 3 , the tumor-bearing mice model would be used for further experiments.…”

“…When the volumes of MDA-MB-231 tumor or MCF-7 tumor reached 60-250 mm 3 , the BALB/c nude mice were divided into groups randomly and received an i.v. injection of 200 μL PBS or PBS containing the different nanoparticle preparations (i.e., UCNPs, RBC-UCNPs, and CCm 231 -UCNPs) at the concentration of 5 mg mL −1 via the tail vein.…”

miR‑31‑5p may enhance the efficacy of chemotherapy with Taxol and cisplatin in TNBC

“…miR-31 overexpression increases the sensitivity of TNBC to TAX and DDP treatment. TNBC is an aggressive cancer with a high risk of relapse within the first 3-5 years after the completion of adjuvant chemotherapy treatments (34). The potential role of miR-31-5p in chemotherapy resistance was then investigated.…”

Prognostic value of kallikrein-related peptidase 12 (KLK12) mRNA expression in triple-negative breast cancer patients

“…TNBC is a very aggressive subgroup of breast cancer: it is more often diagnosed at younger age, in higher stage, with higher grading and Ki-67 staining and leads to more frequent and earlier local or distant visceral recurrence and shorter survival (Foulkes et al 2010;Hernandez-Aya et al 2011). As TNBC tumors lack steroid hormone receptors or HER2 overexpression, systemic treatment is limited to chemotherapy, andif associated with BRCA mutations -PARP inhibitors (Park et al 2018).…”