Breast cancer (BC) is the second most common cause of cancer-related deaths in women worldwide. The availability of reliable biomarkers of response/resistance to cancer treatments would benefit patients and clinicians allowing for a better selection of BC patients most likely to respond to a specific treatment. Phosphatidylinositol 3-kinase (PI3K) enzymes are involved in numerous cellular- functions and processes. The gene encoding for PI3K catalytic subunit p110α is mutated in 20-40% of BC. We performed a meta-analysis of the current literature on randomized clinical trials, investigating the role of PIK3CA mutational status as prognostic factor and predictor of response to anti-cancer treatments. Overall 1929 cases were included. The pooled analysis confirmed that the presence of a PIK3CA mutation represents an independent negative prognostic factor (HR = 1.67, 95% CI: 1.15-2.43; p = 0.007) in BC, as previously reported. Since PI3K signalling is also a result of other pathways’ hyperactivation, further investigation of potential biomarkers able to predict likelihood of response to anti-PI3K/mTOR, anti-HER2 and other TKRs is warranted in future randomized clinical trials. This article is protected by copyright. All rights reserved

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, metastatic breast cancer has a poor prognosis. In an era of personalized medicine, there is an urgent need for better knowledge of the biology leading to the disease, which can lead to the design of increasingly accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the fibroblast growth factor receptor (FGFR) pathway, triggered by specific ligands. The Fibroblast Growth Factor Receptors/Fibroblast Growth Factors (FGFRs/FGFs) axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of FGFR mutations, which lead to tumor formation and summarizes the state-of-the-art therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC.

Breast cancer (BC) is the most common cancer in women worldwide. One in eight women will develop the disease in her lifetime. Notwithstanding the incredible progress made in this field, BC still represents the second most common cause of cancer-related death in women. Targeted drugs have revolutionised breast cancer treatment and improved the prognosis as well as the life expectancy of millions of women. However, the phenomenon of primary and secondary pharmacological resistance is becoming increasingly evident, limiting the efficacy of these agents and calling for a better in-depth knowledge and understanding of the biology as well as the biochemical crosstalk underlying the disease. The advent of laboratory technologies in the clinical setting such as the routine use of next generation sequencing has allowed identification of new genetic alterations as well as providing a precise picture of the molecular landscapes of each tumour. Consequently, new specific therapeutic approaches are becoming available to minimise or delay the occurrence of resistance. In this review, we analyse the latest research and news from the clinical development side for each BC subtype.

Over the last two decades, many studies have demonstrated that the insulin-like growth factor-1 (IGF-1) is involved in a number of patho-physiological processes, as well as in the development of different types of solid tumors, including breast cancer (BC). Preclinical and clinical data showed that IGF-1 receptor (R) is overexpressed and hyper-phosphorylated in several subtypes of BCs. The central implications of this pathway in tumor cell proliferation and metastasis make it an important therapeutic target. Moreover, the IGF-1 axis has shown strong interconnection with estrogen regulation and endocrine therapy, suggesting a possible solution to anti-estrogen resistance. IGF-1R might also interfere with other pivotal therapeutic strategies, such as anti HER2 treatments and mTOR inhibitors; several clinical trials are ongoing evaluating the role of IGF-1R inhibition in modulating resistance mechanisms to target therapies. Our aim is to offer an overview of the most recent and significant field of application of IGF-1 inhibitors and relevant therapeutic strategies, weighing their possible future impact on clinical practice.