Editorial: Optimizing treatment strategy in early breast cancer: less is more, or more is better? No abstract available

Harmonizing gene signatures to predict benefit from adjuvant chemotherapy in early breast cancer Purpose of review Breast cancer is a heterogeneous disease, including different subtypes with their own biology, prognosis, clinical characteristics and treatment. To date, traditional clinical and pathological determinants remain the main factors guiding treatment decision-making; however, the development of multigene assays improved the ability to predict the risk of recurrence in patients with early-stage breast cancer. These tools underwent an extensive independent validation and have already been partly incorporated into clinical practice. Recent findings The current article summarizes current evidence for the use of the different genomic assays in clinical practice, their characteristics and validation studies. A few studies comparing available genomic assays revealed that they provide different information with a modest correlation and that they are not interchangeable; other trials are currently ongoing in this setting. Summary Variability across different gene signatures may be a challenge for the optimal management of the individual patient, hence each assay should be used for the clinical setting in which it has been validated.

Role of dose-dense chemotherapy in high-risk early breast cancer Purpose of review Adjuvant chemotherapy for breast cancer significantly reduces the risk of recurrence and improves overall survival (OS). The purpose of the current article is to review available evidence on dose-dense chemotherapy, also focusing on special population, including premenopausal women and those with HER2-positive disease. Recent findings A recent patient-level meta-analysis showed that the use of dose-dense chemotherapy is associated with significant reduction in disease recurrence, breast cancer mortality and improvement in OS. The benefit of dose-dense chemotherapy is irrespective from HER2 status, although women with HER2-positive disease enrolled in trials included in the meta-analysis did not receive the current standard of treatment with anti-HER2 agents. Among premenopausal women, dose-dense chemotherapy improved OS, and thus should be considered standard of care for them. Summary In conclusion, high-risk early stage breast cancer patients should be treated with (neo)adjuvant dose-dense anthracycline-based chemotherapy followed by paclitaxel. In the era of trastuzumab, the benefit of dose-dense chemotherapy is still unclear for patients with HER2-positive breast cancer.

Window of Opportunity trials for biomarker discovery in breast cancer Purpose of review Window of Opportunity (WOO) studies have gain their place in current clinical and translational research in breast cancer patients. This review provides current information and future applications of this specific type of research. Recent findings So far, WOO trials in breast cancer patients have demonstrated their utility in breast cancer research as: first they allow administering a treatment for a short period of time to treatment-naïve patients whose tumors have not developed mechanisms of resistance or heterogeneity because of previous therapies. Second, it brings a unique opportunity for translational research providing easy access to tumor tissue in order to evaluate antitumor effect from initial biopsy and from surgical resection specimen. They provide the perfect scenario for biomarker discovery and validation in an efficient and timely manner and valuable information about drug pharmacodynamics. Several issues need to be contemplated when designing and performing this type of trials including choice of a biological surrogate endpoint of efficacy as standard clinical activity endpoints are not feasible. Summary Despite some limitations like the absence of information about secondary mechanisms of resistance, WOO trials represent an important support for drug development and biomarker discovery in breast cancer patients.

Strategies to prevent brain metastasis Purpose of review The current article reviews the state of art of prevention strategies for brain metastases from solid tumors and touches both old pivotal studies and new directions of personalized molecular approaches. Recent findings Prophylactic cranial irradiation (PCI) has a definite role in the prevention of relapse into the brain for patients with small cell lung cancer (SCLC) responding to chemotherapy and radiotherapy as it prolongs overall survival (OS). However, the risk of late cognitive deficit following whole brain radiotherapy (WBRT) in this patient population is still not well known. Conversely, PCI significantly reduces the incidence of brain metastases and prolongs the disease-free interval in patients with non-SCLC (NSCLC), but does not improve OS thus far. Pharmacologic prevention is a new concept driven by the efficacy of targeted agents on macrometastases from specific molecular subgroups. Summary The future challenges for prevention of brain metastases are represented by the identification of subgroups of patients at higher risk of relapse into the brain coupled with either new WBRT strategies to better preserve cognition or effective molecular agents to target micrometastases.

Integrated treatment of brain metastases Purpose of review Optimal treatment of brain metastases has been limited to local treatment with few systemic options. Increasing use of systemic targeted therapies, chemotherapy and immunotherapy and combination of local and systemic treatments has resulted in plethora of publications. We review the existing evidence for individual treatments and new evidence for the integration of systemic and combination of local treatments. Recent findings Encouraging efficacy of systemic therapies supports combination of systemic and local treatment albeit with little randomized trial data. Efficacy particularly of targeted agents provides an opportunity to delay local treatments including radiosurgery and whole brain radiotherapy. Randomized trials testing the integration of surgery, radiotherapy and radiosurgery are reviewed with emphasis on patient relevant endpoints to guide the clinician in the choice and sequence of treatments and integrating systemic and local therapies. Summary There is increasing tendency to use focused radiation for single and oligometastases with or without surgery and decline in whole brain radiotherapy which is limited to multiple metastases in tumours without effective systemic options. Systemic therapies have promising intracranial efficacy and the sequence and combination with localized radiation is awaiting trials. Changes in practice with a move to primary systemic treatment for brain metastases without radiation, should be undertaken with caution and close monitoring.

Management of leptomeningeal carcinomatosis and challenges of trial design Purpose of review Highlight recent data in lung and breast cancer leptomeningeal disease and address clinical trials that are open for patients. Recent findings Patients with lung and breast cancer leptomeningeal disease have survival outcomes of less than 1 year, despite advances in treatment strategy. Efforts to develop liquid biopsy biomarkers of disease progression from cerebrospinal fluid and plasma are underway. There are over 10 clinical trials open for patients with leptomeningeal disease, half of which use immunotherapy. Summary Consortium-based, multicenter clinical trials for patients with leptomeningeal disease are urgently needed to expand the treatment armamentarium.

Current strategies for vaccination in glioblastoma Purpose of review Immunotherapy is viewed as a promising approach for glioblastoma and, in particular, therapeutic vaccines are being intensively studied. Here, we review results provided by recent clinical trials of glioblastoma vaccination and discuss the required strategies to optimize such approaches. Recent findings Two studies showed the feasibility of generating mutation-derived personalized vaccines in the short time frame given by the fast course of disease in glioblastoma. However, one of these demonstrated lack of mutation-derived cell surface presented MHC class I or II peptides in tumors with low mutational burden. Summary Whereas glioblastoma vaccines are well tolerated, impact on patient survival has yet to be proven. Combinations with immune checkpoint inhibitors are being tested, but strategies aiming at targeting the tumor microenvironment should be implemented as well. Finally, accurate immunomonitoring should be promoted in order to identify the best vaccine strategies, alone or in combination.

Diffuse intrinsic pontine glioma: molecular landscape and emerging therapeutic targets Purpose of review Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood brainstem malignancy. Despite advances in understanding of the molecular underpinnings of the tumor in the past decade, the dismal prognosis of DIPG has thus far remained unchanged. This review seeks to highlight promising therapeutic targets within three arenas: DIPG cell-intrinsic vulnerabilities, immunotherapeutic approaches to tumor clearance, and microenvironmental dependencies that promote tumor growth. Recent findings Promising therapeutic strategies from recent studies include epigenetic modifying agents such as histone deacetylase inhibitors, bromodomain and extra-terminal motif (BET) protein inhibitors, and CDK7 inhibitors. Tumor-specific immunotherapies are emerging. Key interactions between DIPG and normal brain cells are coming to light, and targeting critical microenvironmental mechanisms driving DIPG growth in the developing childhood brain represents a new direction for therapy. Summary Several DIPG treatment strategies are being evaluated in early clinical trials. Ultimately, we suspect tha