Breast cancer

Abstract

Breast cancer is still the most common cancer worldwide. But the way breast cancer is viewed has changed drastically since its molecular hallmarks were extensively characterised, now including immunohistochemical markers (eg, ER, PR, HER2 [ERBB2], and proliferation marker protein Ki-67 [MKI67]), genomic markers (eg, BRCA1, BRCA2, and PIK3CA), and immunomarkers (eg, tumour-infiltrating lymphocytes and PD-L1). New biomarker combinations are the basis for increasingly complex diagnostic algorithms. Neoadjuvant combination therapy, often including targeted agents, is a standard of care (especially in HER2-positive and triple-negative breast cancer), and the basis for de-escalation of surgery in the breast and axilla and for risk-adapted post-neoadjuvant strategies. Radiotherapy remains an important cornerstone of breast cancer therapy, but de-escalation schemes have become the standard of care. ER-positive tumours are treated with 5-10 years of endocrine therapy and chemotherapy, based on an individual risk assessment. For metastatic breast cancer, standard therapy options include targeted approaches such as CDK4 and CDK6 inhibitors, PI3K inhibitors, PARP inhibitors, and anti-PD-L1 immunotherapy, depending on tumour type and molecular profile. This range of treatment options reflects the complexity of breast cancer therapy today.

Efficacy and Safety of Anti-PD-1/ PD-L1 Monotherapy for Metastatic Breast Cancer: Clinical Evidence

“…Immunotherapy comprises a promising and tolerable new area in breast cancer therapy, and immune checkpoint blocking is one of the most extensively used active immunotherapy. Excessive activation of T cells can be prevented by immune checkpoint, which is function as a protective molecule in immune system of human, subsequently maintaining self-tolerance and reduce excessive auto-immune reactions ( Loibl et al, 2021 ). Immune checkpoint molecules are reported to be overexpressed in malignancy cells and facilitate tumor cells to escape immune surveillance and killing by human immune system.…”

“…By combining with the B7 globulin family ligand PD-L1, PD-1 is activated and subsequently limiting T-cell activity, prohibiting over-active autoimmunity and immunity ( Ademuyiwa et al, 2012 ; Liu et al, 2013 ). Such interactions function differently in normal tissues and tumor cells: in normal tissues, by restricting inflammatory activities during infections, PD-1/PD-L1 interactions exert protection effect against excessive tissue damage ( Wang et al, 2019 ); in tumor cells, such interaction resulted in immune exhaustion and downregulation of immune response ( Loibl et al, 2021 ). PD-1/PD-L1 interactions were also reported in breast cancer, and the expression of PD-1/PD-L1 was confirmed to be closely related to the effect of checkpoint inhibitors ( Mittendorf et al, 2015 ; Salatino et al, 2018 ; Zhu et al, 2018 ).…”

Valproic Acid and Breast Cancer: State of the Art in 2021

“…TNBC has the worst prognosis of all the BC subtypes and is treated with systemic chemotherapy to which it responds better than other subtypes. Unfortunately, the use of traditional cytostatics (cisplatin, paclitaxel) is limited by numerous side effects (bone marrow damage, severe renal failure, peripheral neuropathies), as well as the occurrence of resistance to therapies [ 31 , 32 , 33 , 34 ]. Due to the lack of recognized molecular targets for therapy, TNBC is an object of interest for clinical trials with novel treatment approaches [ 13 ].…”

Inhibition of CDK4/6 as Therapeutic Approach for Ovarian Cancer Patients: Current Evidences and Future Perspectives

“…CDK4/6i have proven to be highly effective in the treatment of advanced stage estrogen receptor-positive HER2-negative breast cancer and, in these patients, the combination of CDK4/6i and hormonal therapy represents now the standard of care [ 106 ].…”