Cancer Screening Behaviors and Associations with Childhood Trauma, Resiliency, and Patient–Provider Relationships: Findings from an Exploratory Study of Appalachian Cervical Cancer Survivors

Introduction: Adverse childhood experiences (ACEs) are associated with increased cancer risk. ACEs may affect this risk in a variety of ways, including cancer screening compliance. ACEs can contribute to mistrust in the medical profession, inhibit patient­–provider relationships and cause at-risk individuals to miss critical access points to preventive services. Protective factors may play an important role in mitigating ACE-related consequences by supporting resiliency. Purpose: This study assesses the associations between ACEs, protective factors, patient–provider relationships, stage of cancer at diagnosis, and cancer screening behaviors for West Virginia (WV) cervical cancer survivors. Methods: WV cervical cancer survivors diagnosed between 2000 and 2020 were mailed a survey which included questions on demographic information and cancer screening behaviors, alongside three scales to measure depth of patient–provider relationships, ACEs, and protective factors. Results: Ninety participants completed the survey. ACEs were associated with weaker patient–provider relationships (p \u3c .01) and fewer protective factors (p \u3c .01). More protective factors were associated with stronger patient–provider relationships (p \u3c .01), earlier stage of cancer at diagnosis (p \u3c .05) and positive cancer screening behaviors. Positive cancer screening behaviors were associated with deeper patient–provider relationships (p \u3c .05). A statistically significant model (p = .004) using ACE and resilience scores was able to account for 13% of the explained variability in depth of patient–provider relationships. Implications: These findings suggest an important interplay between ACEs, protective factors, and patient–provider relationships on cancer screening behaviors. Future studies should consider these variables in different populations. In addition, interventions focused on enhancing patient–provider relationships and supporting acquisition of protective factors should be considered

Receipt of Guideline-Concordant Care Among Older Women With Stage I-III Breast Cancer: A Population-Based Study

Background: This study examined receipt of guideline-concordant care (GCC) according to evidence-based treatment guidelines and quality measures and specific types of treatment among older women with breast cancer. Patients and Methods: A total of 142,433 patients aged ≥66 years diagnosed with stage I–III breast cancer between 2007 and 2011 were identified in the SEER-Medicare linked database. Algorithms considering cancer characteristics and the appropriate course of care as per guidelines versus actual care received determined receipt of GCC. Multivariable logistic regression estimated the likelihood of GCC and specific types of treatment for women aged ≥75 versus 66 to 74 years. Results: Overall, 39.7% of patients received GCC. Patients diagnosed at stage II or III, with certain preexisting conditions, and of nonwhite race were less likely to receive GCC. Patients with hormone-negative tumors, higher grade tumors, and greater access to oncology care resources were more likely to receive GCC. Patients aged ≥75 years were approximately 40% less likely to receive GCC or adjuvant endocrine therapy, 78% less likely to have any surgery, 61% less likely to have chemotherapy, and about half as likely to have radiation therapy than those aged 66 to 74 years. Conclusions: Fewer than half of older women with breast cancer received GCC, with the lowest rates observed among the oldest age groups, racial/ethnic minorities, and women with later-stage cancers. However, patients with more aggressive tumor characteristics and greater access to oncology resources were more likely to receive GCC. Considering that older women have the highest incidence of breast cancer and that many are diagnosed at stages requiring more aggressive treatment, efforts to increase rates of earlier stage diagnosis and the development of less toxic treatments could help improve GCC and survival while preserving quality of life

Dysregulation of metabolic-associated pathways in muscle of breast cancer patients: preclinical evaluation of interleukin-15 targeting fatigue

Background Breast cancer patients report a perception of increased muscle fatigue, which can persist following surgery and standardized therapies. In a clinical experiment, we tested the hypothesis that pathways regulating skeletal muscle fatigue are down-regulated in skeletal muscle of breast cancer patients and that different muscle gene expression patterns exist between breast tumour subtypes. In a preclinical study, we tested the hypothesis that mammary tumour growth in mice induces skeletal muscle fatigue and that overexpression of the cytokine interleukin-15 (IL-15) can attenuate mammary tumourinduced muscle fatigue. Methods Early stage non-metastatic female breast cancer patients (n = 14) and female non-cancer patients (n = 6) provided a muscle biopsy of the pectoralis major muscle during mastectomy, lumpectomy, or breast reconstruction surgeries. The breast cancer patients were diagnosed with either luminal (ER+ /PR+ , n = 6), triple positive (ER+ /PR+ /Her2/neu+ , n = 5), or triple negative (ER/PR/Her2/neu, n = 3) breast tumours and were being treated with curative intent either with neoadjuvant chemotherapy followed by surgery or surgery followed by standard post-operative therapy. Biopsies were used for RNA-sequencing to compare the skeletal muscle gene expression patterns between breast cancer patients and non-cancer patients. The C57BL/6 mouse syngeneic mammary tumour cell line, E0771, was used to induce mammary tumours in immunocompetent mice, and isometric muscle contractile properties and fatigue properties were analysed following 4 weeks of tumour growth. Results RNA-sequencing and subsequent bioinformatics analyses revealed a dysregulation of canonical pathways involved in oxidative phosphorylation, mitochondrial dysfunction, peroxisome proliferator-activated receptor signalling and activation, and IL-15 signalling and production. In a preclinical mouse model of breast cancer, the rate of muscle fatigue was greater in mice exposed to mammary tumour growth for 4 weeks, and this greater muscle fatigue was attenuated in transgenic mice that overexpressed the cytokine IL-15. Conclusions Our data identify novel genes and pathways dysregulated in the muscles of breast cancer patients with early stage non-metastatic disease, with particularly aberrant expression among genes that would predispose these patients to greater muscle fatigue. Furthermore, we demonstrate that IL-15 overexpression can attenuate muscle fatigue associated with mammary tumour growth in a preclinical mouse model of breast cancer. Therefore, we propose that skeletal muscle fatigue is an inherent consequence of breast tumour growth, and this greater fatigue can be targeted therapeutically

The Stem Cell Phenotype of Aggressive Breast Cancer Cells

Aggressive cancer cells are characterized by their capacity to proliferate indefinitely and to propagate a heterogeneous tumor comprised of subpopulations with varying degrees of metastatic propensity and drug resistance properties. Particularly daunting is the challenge we face in the field of oncology of effectively targeting heterogeneous tumor cells expressing a variety of markers, especially those associated with a stem cell phenotype. This dilemma is especially relevant in breast cancer, where therapy is based on traditional classification schemes, including histological criteria, differentiation status, and classical receptor markers. However, not all patients respond in a similar manner to standard-of-care therapy, thereby necessitating the need to identify and evaluate novel biomarkers associated with the difficult-to-target stem cell phenotype and drug resistance. Findings related to the convergence of embryonic and tumorigenic signaling pathways have identified the embryonic morphogen Nodal as a promising new oncofetal target that is reactivated only in aggressive cancers, but not in normal tissues. The work presented in this paper confirms previous studies demonstrating the importance of Nodal as a cancer stem cell molecule associated with aggressive breast cancer, and advances the field by providing new findings showing that Nodal is not targeted by standard-of-care therapy in breast cancer patients. Most noteworthy is the linkage found between Nodal expression and the drug resistance marker ATP-binding cassette member 1 (ABCA1), which may provide new insights into developing combinatorial approaches to overcome drug resistance and disease recurrence

The Stem Cell Phenotype of Aggressive Breast Cancer Cells

Aggressive cancer cells are characterized by their capacity to proliferate indefinitely and to propagate a heterogeneous tumor comprised of subpopulations with varying degrees of metastatic propensity and drug resistance properties. Particularly daunting is the challenge we face in the field of oncology of effectively targeting heterogeneous tumor cells expressing a variety of markers, especially those associated with a stem cell phenotype. This dilemma is especially relevant in breast cancer, where therapy is based on traditional classification schemes, including histological criteria, differentiation status, and classical receptor markers. However, not all patients respond in a similar manner to standard-of-care therapy, thereby necessitating the need to identify and evaluate novel biomarkers associated with the difficult-to-target stem cell phenotype and drug resistance. Findings related to the convergence of embryonic and tumorigenic signaling pathways have identified the embryonic morphogen Nodal as a promising new oncofetal target that is reactivated only in aggressive cancers, but not in normal tissues. The work presented in this paper confirms previous studies demonstrating the importance of Nodal as a cancer stem cell molecule associated with aggressive breast cancer, and advances the field by providing new findings showing that Nodal is not targeted by standard-of-care therapy in breast cancer patients. Most noteworthy is the linkage found between Nodal expression and the drug resistance marker ATP-binding cassette member 1 (ABCA1), which may provide new insights into developing combinatorial approaches to overcome drug resistance and disease recurrence

Breast Cancer Pathology, Receptor Status, and Patterns of Metastasis in a Rural Appalachian Population

Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with more triple-negative phenotypes. We reviewed clinical records for tumor receptor status and time to distant metastasis. Body mass index, tumor size, grade, nodal status, and receptor status were related to metastatic patterns. For 687 patients, 13.8% developed metastases to bone (n=42) or visceral sites (n=53). Metastases to viscera occurred within five years, a latent period which was shorter than that for bone (P=0.042). More women with visceral metastasis presented with grade 3 tumors compared with the bone and nonmetastatic groups (P=0.0002). There were 135/574 women (23.5%) with triple-negative breast cancer, who presented with lymph node involvement and visceral metastases (68.2% versus 24.3%; P=0.033). Triple-negative tumors that metastasized to visceral sites were larger (P=0.007). Developing a visceral metastasis within 10 years was higher among women with triple-negative tumors. Across all breast cancer receptor subtypes, the probability of remaining distant metastasis-free was greater for brain and liver than for lung. The excess risk of metastatic spread to visceral organs in triple-negative breast cancers, even in the absence of positive nodes, was combined with the burden of larger and more advanced tumors

How COVID-19 Highlights an Ongoing Pandemic of Neglect and Oppression When It Comes to Women's Reproductive Rights.

The coronavirus disease-19 (COVID-19) pandemic has exposed an underlying pandemic of neglect affecting women's reproductive rights, particularly in the provision of abortion services and maternity care. The systemic neglect in the Australian context has resulted in a rise in demand for the services provided by privately practising midwives (PPMs) that is not matched by systemic support for, nor recognition of, women choosing to birth at home. As a result, PPMs are unable to meet the rise in demand, which in itself reflects decades of limited State support for the choice to birth at home and opposition by incumbent stakeholders in the provision of maternity care to healthy women with low-risk pregnancies. We discuss the historical backdrop to these currently erupting issues, along with the real reasons for the opposition to PPMs in Australia. Finally, we offer solutions to this ongoing issue

How COVID-19 highlights an ongoing pandemic of neglect and oppression when it comes to women's reproductive rights

The coronavirus disease-19 (COVID-19) pandemic has exposed an underlying pandemic of neglect affecting women's reproductive rights, particularly in the provision of abortion services and maternity care. The systemic neglect in the Australian context has resulted in a rise in demand for the services provided by privately practising midwives (PPMs) that is not matched by systemic support for, nor recognition of, women choosing to birth at home. As a result, PPMs are unable to meet the rise in demand, which in itself reflects decades of limited State support for the choice to birth at home and opposition by incumbent stakeholders in the provision of maternity care to healthy women with low-risk pregnancies. We discuss the historical backdrop to these currently erupting issues, along with the real reasons for the opposition to PPMs in Australia. Finally, we offer solutions to this ongoing issue

Breast Cancer Survivors’ Perceptions of Prevention versus Control of Future Cancer Recurrence

Background. The Institute of Medicine has established Survivorship Care Planning as a critical component of cancer care to ensure that cancer survivors receive the appropriate follow-up care in a timely manner and support cancer survivors in dealing with the risk of recurrence, yet little is known about how cancer survivors think about preventing or controlling future cancer recurrence. This study sought to assess breast cancer women’s perceived prevention and perceived control of future cancer recurrence. Methods. Women with a history of breast cancer (n=114) were surveyed, and data were analyzed using concurrent mixed methods. Binary logistic regression models examined predictors of perceived prevention and perceived control of cancer recurrence. Results. Most women perceived that they could control cancer recurrence (89%); few (30%) perceived that they could prevent cancer recurrence. Women reported components of the timeline (e.g., early diagnosis), identity (e.g., cancer in body), causes (e.g., hereditary), consequences (e.g., witness success), and cure/control (e.g., exercise) or lack of cure/control. Women who reported lack of control were less likely to perceive that they could control cancer recurrence. Women who reported causes were less likely to perceive that they could prevent or control cancer recurrence. Conclusions. Women’s perceptions about the prevention and control of cancer recurrence are important and different factors in the minds of women with breast cancer. Most women believed they could control cancer recurrence; however, few believed they could prevent cancer recurrence. Interventions to focus on control of cancer recurrence, focusing on evidence-based clinical and lifestyle interventions, are needed