Susan G. Komen Big Data for Breast Cancer Initiative: How Patient Advocacy Organizations Can Facilitate Using Big Data to Improve Patient Outcomes.

Integrating different types of data, including electronic health records, imaging data, administrative and claims databases, large data repositories, the Internet of Things, genomics, and other omics data, is both a challenge and an opportunity that must be tackled head on. We explore some of the challenges and opportunities in optimizing data integration to accelerate breast cancer discovery and improve patient outcomes. Susan G. Komen convened three meetings (2015, 2017, and 2018) with various stakeholders to discuss challenges, opportunities, and next steps to enhance the use of big data in the field of breast cancer. Meeting participants agreed that big data approaches can enhance the identification of better therapies, improve outcomes, reduce disparities, and optimize precision medicine. One challenge is that databases must be shared, linked with each other, standardized, and interoperable. Patients want to be active participants in research and their own care, and to control how their data are used. Many patients have privacy concerns and do not understand how sharing their data can help to effectively drive discovery. Public education is essential, and breast cancer researchers who are skilled in using and analyzing big data are needed. Patient advocacy groups can play multiple roles to help maximize and leverage big data to better serve patients. Komen is committed to educating patients on big data issues, encouraging data sharing by all stakeholders, assisting in training the next generation of data science breast cancer researchers, and funding research projects that will use real-life data in real time to revolutionize the way breast cancer is understood and treated.

Global analysis of advanced/metastatic breast cancer: Decade report (2005-2015).

Approximately 0.5 million people worldwide die from metastatic breast cancer (mBC) every year. This manuscript provides an overview on the status of mBC in several regions of the world, highlighting the gaps in care, resources, and support available for patients with mBC. Primary research was conducted in 2015 and 2016, comprising four global qualitative and quantitative surveys of approximately 15,000 individuals in 34 countries. Secondary research was conducted using literature reviews of peer-reviewed publications, patient survey reports, and media or online articles. There have been modest improvements in mBC outcomes over the past decade. Patients are not provided with adequate information about mBC. There is a need for open discussion with patients and caregivers about realistic goals; however, physicians are not trained in communicating with patients about their disease. Maintaining patients' quality of life is a crucial goal; however, this has not improved, and in some cases, may have declined in the past decade. Public awareness and understanding of mBC is limited, with damaging consequences for patients and caregivers. Issues affecting employment remain relevant to patients with mBC and their caregivers. Globally, mBC is associated with a substantial economic burden. Relationships with caregivers are crucial to patients with mBC, and caregiver support needs are often overlooked. A strong and united global effort among healthcare professionals, including clinicians, oncologists, pharmaceutical manufacturers, payers, and policy makers, and with advocates, families, and patients, is necessary to improve the outcome and quality of life for patients with mBC.

A chemokine, SDF-1, reduces the effectiveness of multiple axonal repellents and is required for normal axon pathfinding.

Altering the concentrations of cyclic nucleotides within nerve cells can dramatically change their responses to axonal guidance cues, but the physiological signals that might induce such alterations are unknown. Here we show that the chemokine stromal cell-derived factor 1 (SDF-1) reduces the repellent activities of slit-2 on cultured retinal ganglion cell axons, of semaphorin 3A on dorsal root ganglion sensory axons, and of semaphorin 3C on sympathetic axons. This is a modulatory effect because SDF-1 has no detectable attractive or repellent effects on retinal or DRG axons by itself. This modulation is mediated through CXCR4, the receptor of SDF-1, and a pertussis toxin-sensitive G-protein-coupled signaling pathway that induces an elevation of cAMP. The spinal cords of CXCR4 mutant mice contain hyperfasciculated and aberrantly projecting axons. These results suggest that SDF-1 plays an essential role in modulating axonal responsiveness to various known guidance cues through a cyclic nucleotide-dependent signaling pathway.

Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve.

Developing neurons accurately position their somata within the neural tube to make contact with appropriate neighbors and project axons to their preferred targets. Taking advantage of a collection of genetically engineered mouse mutants, we now demonstrate that the behavior of somata and axons of the facial nerve is regulated independently by two secreted ligands for the transmembrane receptor neuropilin 1 (Nrp1), the semaphorin Sema3A and the VEGF164 isoform of Vascular Endothelial Growth Factor. Although Sema3A is known to control the guidance of facial nerve axons, we now show that it is not required for the pathfinding of their somata. Vice versa, we find that VEGF164 is not required for axon guidance of facial motor neurons, but is essential for the correct migration of their somata. These observations demonstrate, for the first time, that VEGF contributes to neuronal patterning in vivo, and that different compartments of one cell can be co-ordinately patterned by structurally distinct ligands for a shared receptor.