Brain metastases from breast cancer (BCBM) constitute the second most common cause of brain metastasis (BM), and the incidence of these frequently lethal lesions is currently increasing, following better systemic treatment. Patients with ER-negative and HER2-positive metastatic breast cancer (BC) are the most likely to develop BM, but if this diagnosis remains associated with a worse prognosis, long survival is now common for patients with HER2-positive BC. BCBM represents a therapeutic challenge that needs a coordinated treatment strategy along international guidelines. Surgery has always to be considered when feasible. It is now well established that stereotaxic radiosurgery allows for equivalent control and less-cognitive toxicities than whole-brain radiation therapy, which should be delayed as much as possible. Medical treatment for BCBM is currently a rapidly evolving field. It has been shown that the blood–brain barrier (BBB) is often impaired in macroscopic BM, and several chemotherapy regimens, antibody–drug conjugates and tyrosine-kinase inhibitors have been shown to be active on BCBM and can be part of the global treatment strategy. This paper provides an overview of the therapeutic option for BCBM that is currently available and outlines potential new approaches for tackling these deadly secondary tumours.

In squamous cell carcinoma (SCC), tissue invasion by collectively invading cells requires physical forces applied by tumor cells on their surrounding extracellular matrix (ECM). Cancer-related ECM is composed of thick collagen bundles organized by carcinoma-associated fibroblasts (CAF) within the tumor stroma. Here, we show that SCC cell collective invasion is driven by the matrix-dependent mechano-sensitization of EGF signaling in cancer cells. Calcium (Ca²⁺) was a potent intracellular second messenger that drove actomyosin contractility. Tumor-derived matrix stiffness and EGFR signaling triggered increased intracellular Ca²⁺ through Ca_V1.1 expression in SCC cells. Blocking L-type calcium channel expression or activity using Ca²⁺ channel blockers verapamil and diltiazem reduced SCC cell collective invasion both in vitro and in vivo. These results identify verapamil and diltiazem, two drugs long used in medical care, as novel therapeutic strategies to block the tumor-promoting activity of the tumor niche. Significance: This work demonstrates that calcium channels blockers verapamil and diltiazem inhibit mechano-sensitization of EGF-dependent cancer cell collective invasion, introducing potential clinical strategies against stromal-dependent collective invasion. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/18/5229/F1.large.jpg. Cancer Res; 78(18); 5229–42. ©2018 AACR.

Artificial intelligence (AI) is progressively spreading through the world of health, particularly in the field of oncology. AI offers new, exciting perspectives in drug development as toxicity and efficacy can be predicted from computer-designed active molecular structures. AI-based in silico clinical trials are still at their inception in oncology but their wider use is eagerly awaited as they should markedly reduce durations and costs. Health authorities cannot neglect this new paradigm in drug development and should take the requisite measures to include AI as a new pillar in conducting clinical research in oncology.

Breast cancer (BC) is the most prevalent malignancy in women worldwide. Despite most cases being diagnosed in the early stages, patients typically require a multimodal treatment approach. This typically involves a combination of surgery, radiotherapy, systemic treatments (including chemotherapy or immunotherapy), targeted therapy, and endocrine therapy, depending on the disease subtype and the risk of recurrence. Moreover, patients with BC and germline mutations in the breast cancer genes 1 or 2 (BRCA1/BRCA2), (gBRCAm), who are typically young women, often require more aggressive therapeutic interventions. These mutations present unique characteristics that necessitate a distinct treatment approach, potentially influencing the side effect profiles of patients with BC. Regardless of the clear benefit observed with these treatments in terms of reduced recurrence and mortality rates, long-term, treatment-related adverse events occur that negatively affect the health-related quality of life (HRQoL) of BC survivors. Thus, long-term adverse events need to be factored into the treatment decision algorithm of patients with early BC (eBC). Physical, functional, emotional, and psychosocial adverse events can occur and represent a significant concern and a challenge for clinicians, patients, and their families. This review article provides an overview of the various long-term adverse events that patients with eBC may experience, including their associated risk factors, as well as management and prevention strategies. We also explore the evidence of the long-term impact of treatment on the HRQoL of patients with gBRCAm. By providing a comprehensive overview of current evidence and recommendations regarding patients’ HRQoL, we aim to equip clinicians with scientific and clinical knowledge and provide guidance to optimize care and improve long-term outcomes.