Mounting preclinical and clinical evidence continues to support a role for the neuroendocrine system in the modulation of tumor biology and progression. Several studies have shown data supporting a link between chronic stress and cancer progression. Dysregulation of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in promoting angiogenesis, tumor cell proliferation and survival, alteration of the immune response and exacerbating inflammatory networks in the tumor microenvironment. Here, we review how SNS and HPA dysregulation contributes to disturbances in immune cell populations, modifies cancer biology, and impacts immunotherapy response. We also highlight several interventions aimed at circumventing the adverse effects stress has on cancer patients.

Multiple studies suggest that chronic stress accelerates the growth of existing tumors by activating the sympathetic nervous system. Data suggest that sustained adrenergic signaling can induce tumor growth, secretion of pro-inflammatory cytokines, and macrophage infiltration. Our goal was to study the role of adrenergic-stimulated macrophages in ovarian cancer biology. Cytokine arrays were used to assess the effect of adrenergic stimulation in pro-tumoral cytokine networks. An orthotopic model of ovarian cancer was used to assess the in vivo effect of daily restraint stress on tumor growth and adrenergic-induced macrophages. Cytokine analyses showed that adrenergic stimulation modulated pro-inflammatory cytokine secretion in a SKOV3ip1 ovarian cancer cell/U937 macrophage co-culture system. Among these, platelet-derived growth factor AA (PDGF-AA), epithelial cell-derived neutrophil-activating peptide (ENA-78), Angiogenin, vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-5 (IL-5), Lipocalin-2, macrophage migration inhibitory factor (MIF), and transferrin receptor (TfR) were upregulated. Enriched biological processes included cytokine-mediated signaling pathways and positive regulation of cell proliferation. In addition, daily restraint stress increased ovarian cancer growth, infiltration of CD68+ macrophages, and expression of PDGF-AA in orthotopic models of ovarian cancer (SKOV3ip1 and HeyT30), while zoledronic acid, a macrophage-depleting agent, abrogated this effect. Furthermore, in ovarian cancer patients, high PDGFA expression correlated with worse outcomes. Here, it is shown that the adrenergic regulation of macrophages and PDGFA might play a role in ovarian cancer progression.

Cancer is the leading cause of death in Puerto Rico (PR). Hurricane Maria (HM) and its aftermath lead to widespread devastation on the island, including the collapse of the healthcare system. Medically fragile populations, such as cancer survivors, were significantly affected. The goal of this study was to assess the impact of HM on barriers to care, emotional distress, and inflammatory biomarkers among cancer survivors in PR. This exploratory longitudinal study was conducted in health care facilities and community support groups from PR. Cancer survivors (n = 50) and non-cancer participants (n = 50) completed psychosocial questionnaires and provided blood samples that were used to assess inflammatory cytokines levels. Among this cohort, we identified 41 matched cancer survivors/noncancer participants pairs. Data were analyzed through descriptive, frequencies, correlational, and regression analyses. Cancer survivors that were affected by HM reported increased barriers in accessing medical care, which were directly associated with anxiety, perceived stress, and post-traumatic symptomatology. Moreover, being a cancer survivor, predicted more barriers to receiving health care, especially in the first six weeks after the event, after which the effect was attenuated. Several inflammatory cytokines, such as CD31, BDNF, TFF3, Serpin E-1, VCAM-1, Vitamin D BP, and PDGF-AA, were significantly upregulated in cancer survivors while MMP9 and Osteopontin both had significant positive correlations with barriers to care. HM significantly impacted Puerto Ricans psychosocial wellbeing. Cancer survivors had significant barriers to care and showed increased serum inflammatory cytokines but did not show differences in anxiety, stress, and post-traumatic symptoms compared to non-cancer participants. Natural disasters can significantly alter an individual's daily life and lead to psychological distress, particularly in medically fragile populations such as cancer survivors. Hurricane Maria (HM) made landfall in Puerto Rico (PR) on September 20, 2017, as Category 4 storm, killing an estimated 2,975 people and causing an estimated $90 billion in damages 1-3. Widespread devastation included loss of power and potable water infrastructure; destruction of buildings, bridges, and roads; lack of telecommunications; and closing of ports and airports 4. Lack of access to food and clean water was a significant problem for residents of PR 4. Mudslides rendered many roads in rural

Cancer is the leading cause of death in Puerto Rico (PR). Hurricane Maria (HM) and its aftermath lead to widespread devastation in the island, including the collapse of the healthcare system. Medically fragile populations, such as cancer survivors, were significantly affected. The goal of this study was to assess the impact of HM on barriers to care, emotional distress, and inflammatory biomarkers among cancer survivors in PR. This exploratory longitudinal study was conducted in health care facilities and community support groups from PR. Cancer survivors (n=50) and non-cancer participants (n=50) completed psychosocial questionnaires and provided blood samples that were used to assess inflammatory cytokines levels. Data were analyzed through descriptive, frequencies, correlational, and linear regression analyses. Cancer survivors that were affected by HM reported increased barriers in accessing medical care, which were directly associated with anxiety, perceived stress, and post-traumatic symptomatology. Moreover, being a cancer survivor, along with closeness in time from HM predicted more barriers to receiving health care. Several inflammatory cytokines, such as CD31, BDNF, TFF3, Serpin E-1, Vitamin D BP, VCAM-1, Osteopontin, Chitinase 3 like 1, MMP-9 and MIF were significantly upregulated in cancer survivors while BDNF, MMP9 and Osteopontin had significant positive correlations with barriers to care. HM significantly impacted Puerto Ricans psychosocial well-being. Cancer survivors had significant barriers to care and showed increased serum inflammatory cytokines, but did not show differences in anxiety, stress and post-traumatic symptoms compared to non-cancer participants

BackgroundPrevious epidemiological studies aimed at describing characteristics of breast (BC) and ovarian cancer (OC) patients tend to examine Hispanic populations using a mix of individuals that come from ethnically different Hispanic backgrounds. Since most USA cancer statistics do not include cancer data from Puerto Rico (PR), there is a lack of historical and descriptive data analysis for Hispanic women in the island that suffer from these diseases. Therefore, the aim of our study is to provide a comprehensive clinicopathological characterization of BC and OC cases in PR.MethodsOur study consisted of a longitudinal retrospective review of archived pathology reports at Southern Pathology Services (SPS), which mostly serves southwestern PR, from years 2000–2015. After filtering SPS records with pre-established criteria, tumor samples from 3451 BC and 170 OC cases were used for descriptive statistics and analysis using R program.ResultsIn our cohort, the mean age of diagnosis for BC was 60.5 years and 60.3 years for OC. Available data for subtype characterization from BC cases, exhibited an expected subtype distribution that remained stable over time (Luminal A = 68.8%, Luminal B = 9.7%, HER-2 = 6.1% and Triple negative = 15.4%). Additionally, tumor grades distribution varied within different BC subtypes in which the majority of Luminal A tumors were G2 and most Triple negative tumors were G3. For OC cases, available subtype and tumor grade information identified serous histology in 64.71% of all cases and G3 as being the most prevalent tumor grade. Pathology reports revealed that 39.42% of all OC cases were described as late stage, while 50.5% as early stage (by pathological staging).ConclusionOur data suggests that OC and BC subtypes distribution in Hispanic populations from PR are in-line with national averages. In a significant number of BC cases, subtype could not be determined due to study limitations, health insurance coverage, or other reasons described here and may constitute a health disparity. Altogether, and despite these gaps, this study represents one of the most complete reviews of BC and OC in PR and provides an opportunity to further study this population separate from other US Hispanic populations.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-5077-z) contains supplementary material, which is available to authorized users.