Exploring the experiences of women living with metastatic breast cancer [MBC]: A systematic review of qualitative evidence.

PURPOSE: Metastatic breast cancer [MBC] is the leading cause of cancer death in women globally with no cure. Women diagnosed with MBC endure a catastrophic upheaval to multiple aspects of their life and a radically transformed future landscape. Evidence suggests that the provision of care for women living with metastatic breast cancer is inadequate, socially isolating and stigmatising. To date, this topic has received little research attention. To increase understanding of the experiences of women living with MBC, a synthesis of current evidence is required. This paper presents a review of qualitative evidence on women's experiences of MBC. METHODS: A qualitative evidence synthesis [QES] was conducted to synthesise primary qualitative research on the experiences of women living with MBC. Searches were performed of electronic databases Medline, Medline Ovid, PsycINFO, Psych articles, PubMED, CINAHL Complete, Scopus and grey literature databases. The methodological quality of the included studies was appraised using a modified version of the Critical Appraisal Skills Programme [CASP]. Title, abstract, and full-text screening were undertaken. A 'best fit' framework approach using the ARC [Adversity, Restoration, Compatibility] framework was used to guide data extraction and synthesis. Confidence in the findings was assessed using the Grading of Recommendations Assessment, Development and Evaluation, Confidence in the Evidence from Reviews of Qualitative research [GRADE-CERQual]. RESULTS: 28 papers from 21 research studies containing 478 women's experiences of living with MBC were deemed suitable for inclusion in this qualitative evidence synthesis. Findings are presented in a new conceptual framework RAAW [adapted from ARC] for women living with MBC under themes: Reality, Adversity, Adjustment and Wellbeing. Findings revealed that a diagnosis of MBC impacted every aspect of women's lives; this is different to a diagnosis of early breast cancer. An overarching theme of lack of support extended across various facets of their lives. A lack of psychological, emotional, and psychosocial support was evident, with a critical finding that models of care were not fit for purpose. Deficits included a lack of information, knowledge, inclusion in shared decision-making and MDT support, specifically the need for palliative care/oncology support access. Some women living with MBC wanted to be identified as having a chronic illness not a life-limiting illness. Culture and socioeconomic standing influenced the availability of various types of support. The impact of treatment and symptoms had an adverse effect on women's quality of life and affected their ability to adjust. CONCLUSION: This review synthesised the qualitative literature on the experiences of women living with MBC. The ARC framework used in the synthesis was adapted to develop a revised conceptual framework titled RAAW to represent the evidence from this review on experiences for women living with MBC; Reality & Adversity: A diagnosis of MBC; Adjustment: Living with MBC; Wellbeing: Awareness, meaning, engagement [RAAW; MBC].

Treatment and Management of the Clinical Manifestations of Advanced Breast Cancer.

OBJECTIVES: People with advanced breast cancer (ABC) experience complex and debilitating physical symptoms of their disease that can have a profound effect on quality of life. This report provides an overview of the clinical manifestations related to different metastatic sites in ABC and potential oncologic emergencies. DATA SOURCES: Date sources include peer-reviewed papers sourced in electronic databases (CINAHL, MEDLINE, Google Scholar) and national and international best practice guidelines. CONCLUSION: People living with ABC experience multiple symptoms of disease that can impact on quality of life and physical functioning. The most common sites of metastatic disease are bone, lung, liver and brain. Clinical manifestations of ABC include pain, pathologic fractures, pleural effusions, and ascites. Potential oncologic emergencies related to these metastatic sites include hypercalcemia, malignant spinal cord compression, superior vena cava obstruction, and raised intracranial pressure. IMPLICATIONS FOR NURSING PRACTICE: It is important for nurses to have informed knowledge and understanding of these clinical manifestations. This will enable them to be vigilant and perform targeted patient evaluation to assess signs and symptoms with a view to identifying potentially life-threatening emergencies and initiating interventions or appropriate referral or follow-up accordingly.

Development and Implementation of an Online Education Program on Advanced Breast Cancer for European Cancer Nurses: ABC4Nurses Project: a Brief Report.

Breast cancer is now the most commonly diagnosed cancer worldwide. Approximately 30% of those who present with early breast cancer later develop advanced breast cancer (ABC). Additionally, approximately 6% have advanced breast cancer at diagnosis. New treatment options result in an extended lifespan dominated by cycles of deterioration and stable disease. Specialist nurse knowledge is key to multidisciplinary care of people with ABC; however, access to education on ABC for nurses is not universally available in Europe. This paper describes the development and implementation of an online bespoke program on ABC care for specialist and generalist nurses in Europe. The project team is affiliated with the European Oncology Nurses Society (EONS) and comprises specialist breast cancer nurses, oncology nurse academics and breast cancer advocates associated with EUROPA DONNA Turkey, an independent non-profit European breast cancer organisation. The program development involved (1) a systematic review of ABC educational resources for cancer nurses; (2) a modified four-round Delphi study to seek agreement on curriculum content and (3) curriculum development, conversion to an interactive online platform and translation into four European languages. The program evaluation will be guided by Kirkpatrick's framework. The phases described in this short report could guide others involved in developing bespoke cancer education programs.

Clinical experiences of using ports and non-coring needles.

The following case studies describe the use of the Smith Medical implanted ports and Gripper huber needles. Smiths Medical produces a range of implanted ports that include the Port-A-Cath and P.A.S. Port Power P.A.C. systems. The ports are easy to implant, maintain and remove. They are lightweight and have features that are designed to reduce complication rates, including a highly compressed septum to increase needle retention, a titanium chamber with a gouge-resistant floor, a bevelled chamber for optimal rinsing, a round shape to avoid overturning and the Ultralock connection. They are available in various configurations, with single and dual lumens. There is also a needle for power-injection of contrast media for certain types of diagnostic imaging scans (Smith Medical 18). The Gripper Plus needle is designed with an emphasis on safety, effectiveness and patient comfort. These non-coring needles have a bevelled tip that sits flush with the back of the port without impeding the flow of fluid; this also prevents holes forming in the septum (Barton et al, 2018). The needle is available in different gauges and lengths, which can be tailored to reflect individual patient needs and the amount of adipose tissue present. It is essential to select the correct size, which will reduce the risk of dislodgement. The Gripper needles are compatible with paclitaxel and lipid solutions, and are recommended by the National Institute for Occupational Safety and Health (NIOSH) (1999). They are compatible with both the Port-a-Cath and P.A.S. Port Power P.A.C. systems, and can be ordered from the same manufacturer, which has the potential to make ordering, training and support more efficient.

The need for national mandatory guidance on CSTDs.

Closed system transfer devices play a vital role in reducing health professionals' risk of exposure to hazardous drugs. Although recommended as a first line of defence against contamination, they are not widely used. Clear mandatory national guidance is needed to address this.

Survivorship care for postmenopausal breast cancer patients in Ireland: What do women want?

PURPOSE: The aim of this study was to identify the concerns of postmenopausal breast cancer patients in Ireland and inform the development of a survivorship care plan. METHOD: A qualitative participatory approach was used. Focus group interviews (n = 6) with 51 women were undertaken. Following analysis of the focus group discussions, two nominal group technique (NGT) (consensus workshops) involving representatives (n = 17) from each of the six focus groups were held. RESULTS: Ten key issues were highlighted by women in the focus groups and these were prioritised at the consensus workshops. The most important issues in survivorship care planning prioritised by the women were as follows: meet the same healthcare professional at each review visit; contact number of a named person that you can contact if you have any concerns between review visits; at each review visit, have a physical examination and blood tests and explanation from health care professional outlining if follow up scans needed and if not, why not; information on signs and symptoms of recurrence; advice on diet, exercise, healthy lifestyle and advice on coping and pacing yourself; information and management of side effects of therapy-long and short term. CONCLUSION: Survivorship care planning for breast cancer is underdeveloped in Ireland. There is a lack of consensus regarding its provision and a lack of structured approach to its implementation. This study demonstrates the role of postmenopausal breast cancer patients' involvement in identifying their needs and reports that continuity of care was their top priority and the need for an adoption of a survivorship care plan was emphasised by participants.

Use of closed-system drug transfer devices in the handling and administration of MABs.

There is a lack of research and consensus on the long-term risks of occupational exposure to monoclonal antibodies. There is, however, some risk to health professionals who are involved in their preparation and administration. This article discusses the use of closed-system drug transfer devices to minimise exposure, and touches on the importance of aseptic techniques, personal protective equipment, and appropriate education and training for health professionals.

Avoiding accidental exposure to intravenous cytotoxic drugs.

Many cytotoxic drugs have been shown to be mutagenic, teratogenic and carcinogenic with second malignancies known to be associated with several specific cancer drugs. Occupational exposure to cytotoxic drugs presents a signification danger to healthcare staff and unwarranted handling of these drugs should be avoided. Guidelines have been established for the safe handling of hazardous drugs but not all professionals are adhering to these recommendations. Recent environmental studies have demonstrated measurable drug contamination on surfaces even when recommended guidelines are followed. It is therefore imperative that healthcare workers are aware of the potential hazards of antineoplastic agents and employ the recommended precautions to minimise exposure. This article outlines the potential risks associated with exposure to cytotoxic drugs for healthcare staff. The safe-handling precautions required in the storage, preparation, transport, administration and waste disposal of cytotoxic drugs are presented.

Early breast cancer: diagnosis, treatment and survivorship.

Breast cancer is the most common female cancer and globally remains a major public health concern. The diagnosis and treatment of breast cancer continues to develop. Diagnosis is now more precise, surgery is less mutilating and women now have the option of breast conserving therapy with better cosmesis, and without sacrificing survival. Radiotherapy is more targeted and the selection of patients for adjuvant chemotherapy is based not only on prognostic and predictive factors, but also on newer molecular profiling that will ensure that chemotherapy is given to the patients who need and respond to it. These developments all provide a more tailored approach to the treatment of breast cancer. Management now involves a multidisciplinary team approach in order to provide the highest standard of care for patients throughout their cancer journey from diagnosis through treatment and into follow-up care.

Young patients' treatment motivation and satisfaction with orthognathic surgery outcomes: the role of "possible selves".

INTRODUCTION: We investigated how young patients' motivation for orthognathic surgery affected their satisfaction with treatment outcomes. The objective was to explore whether patients' "possible selves" (ie, their ideas of what they might become in the future) and their parents' proxy assessments of the patients' possible selves were significantly correlated with the patients' treatment satisfaction. METHODS: Questionnaire data were collected from 115 former patients (ages, 13-21 at time of surgery) and 117 parents (response rates, 41% and 42%, respectively), with responses from 95 patient-parent pairs. The patients' motivations before surgery were assessed by determining how energized they were by thoughts about themselves after the surgery, and how much they had focused on the outcomes. The parents completed a parallel measure of their children's motivation. Patient satisfaction was determined with the postsurgical patient satisfaction questionnaire. RESULTS: The more emotionally energized the patients had been before the surgery, the more satisfied they were with the outcomes (Spearman rho = .54, P <0.001). Similarly, the more these patients had focused on esthetic changes and improved functioning, the more satisfied they were with the outcomes (Spearman rho = .46, P <0.001; rho = .41, P <0.001, respectively). Parents' recalls of their children's motivation before the surgery were consistent with the children's self-reports (all P <0.001) and correlated with the children's satisfaction (P <0.001 in the energized domain; P <0.01 for the esthetic changes domain). CONCLUSIONS: Young patients' recalls of their possible self-based motivation for orthognathic surgery were highly correlated with their treatment satisfaction. Oral surgeons and orthodontists should discuss with young patients and their parents the patient's motivation during the consultation phase before treatment to assess how energized and focused they are on future treatment outcomes.

Apurinic/apyrimidinic endonuclease activity is associated with response to radiation and chemotherapy in medulloblastoma and primitive neuroectodermal tumors.

PURPOSE: Apurinic/apyrimidinic endonuclease (Ap endo) is a key DNA repair activity that confers resistance to radiation- and alkylator-induced cytotoxic abasic sites in human cells. We assayed apurinic/apyrimidinic endonuclease activity in medulloblastomas and primitive neuroectodermal tumors (PNET) to establish correlates with tumor and patient characteristics and with response to adjuvant radiation plus multiagent chemotherapy. EXPERIMENTAL DESIGN: Ap endo activity was assayed in 52 medulloblastomas and 10 PNETs from patients 0.4 to 21 years old. Ape1/Ref-1, the predominant human Ap endo activity, was measured in 42 medulloblastomas by immunostaining. Cox proportional hazards regression models were used to analyze the association of activity with time to tumor progression (TTP). RESULTS: Tumor Ap endo activity varied 180-fold and was significantly associated with age and gender. Tumor Ape1/Ref-1 was detected almost exclusively in nuclei. In a multivariate model, with Ap endo activity entered as a continuous variable, the hazard ratio for progression after adjuvant treatment in 46 medulloblastomas and four PNETs increased by a factor of 1.073 for every 0.01 unit increase in activity (P < or = 0.001) and was independent of age and gender. Suppressing Ap endo activity in a human medulloblastoma cell line significantly increased sensitivity to 1,3-bis(2-chlororethyl)-1-nitrosourea and temozolomide, suggesting that the association of tumor activity with TTP reflected, at least in part, abasic site repair. CONCLUSIONS: Our data (a) suggest that Ap endo activity promotes resistance to radiation plus chemotherapy in medulloblastomas/PNETs, (b) provide a potential marker of treatment outcome, and (c) suggest clinical use of Ap endo inhibitors to overcome resistance.

Apurinic endonuclease activity in adult gliomas and time to tumor progression after alkylating agent-based chemotherapy and after radiotherapy.

PURPOSE: Apurinic/apyrimidinic endonuclease (Ap endo) is a key DNA repair enzyme that cleaves DNA at cytotoxic abasic sites caused by alkylating agents and radiation. We have observed that human glioma cells deficient in Ap endo activity are hypersensitive to clinically used alkylators (Silber et al., Clin Cancer Res 2002;8:3008.). Here we examine the association of glioma Ap endo activity with clinical response after alkylating agent-based chemotherapy or after radiotherapy. EXPERIMENTAL DESIGN: Cox proportional hazards regression models were used to analyze the relationship of Ap endo activity with time to tumor progression (TTP). RESULTS: In a univariate model with Ap endo activity entered as a continuous variable, the hazard ratio (HR) for progression after alkylator therapy in 30 grade III gliomas increased by a factor of 1.061 for every 0.01 increase in activity (P = 0.013). Adjusting for age, gender, extent of resection, and prior treatment strengthened slightly the association (HR = 1.094; P = 0.003). Similarly, the HR for progression after radiotherapy in 44 grade II and III tumors increased by a factor of 1.069 (P = 0.008). Adjusting for the aforementioned variables had little effect on the association. In contrast, we observed no association between activity and TTP in grade IV gliomas after either alkylator therapy in 34 tumors or radiotherapy in 26 tumors. CONCLUSIONS: Our data suggest that Ap endo activity mediates resistance to alkylating agents and radiation and may be a useful predictor of progression after adjuvant therapy in a subset of gliomas.

The Werner syndrome protein confers resistance to the DNA lesions N3-methyladenine and O6-methylguanine: implications for WRN function.

The Werner syndrome (WS) protein (WRN), a DNA helicase/exonuclease, is required for genomic stability and avoidance of cancer. Current evidence suggests that WRN is involved in the resolution of stalled and/or collapsed replication forks. This function is indicated, in part, by replication defects in WS cells and by hypersensitivity to agents causing major structural aberrations in DNA that block replication. We show here that antisense suppression of WRN in two human glioma cell lines reproduces hallmarks of the drug cytotoxicity profile of WS cells, namely, hypersensitivity to 4-nitroquinoline 1-oxide, camptothecin and hydroxyurea. We also show that antisense-treated cells are hypersensitive to methyl-lexitropsin, a site-specific alkylating agent that produces mainly N3-methyladenine, a cytotoxic and replication-blocking lesion. Antisense-treated cells are hypersensitive to O(6)-methylguanine adducts as well, but only when repair by O(6)-methylguanine-DNA methyltransferase is lacking. Our results illustrate the drug sensitivity caused by deficiency of WRN in a uniform genetic background. They extend the WRN DNA damage sensitivity spectrum to methyl base adducts that can result in blocked replication, and suggest that WRN may be required for resumption of processive replication when incomplete repair of DNA damage leaves blocking lesions at forks. The evidence that highly disparate lesions fall within the purview of WRN, and that abrogating DNA repair can reveal dependence on WRN, suggests that WRN may protect the genome from the lethal, mutagenic and carcinogenic effects of widely diverse DNA damage arising from endogenous processes and environmental agents.

Edmonston measles virus prevents increased cell surface expression of peptide-loaded major histocompatibility complex class II proteins in human peripheral monocytes.

Gamma interferon (IFN-gamma) induces expression of the gene products of the major histocompatibility complex (MHC), whereas IFN-alpha/beta can interfere with or suppress class II protein expression. In separate studies, measles virus (MV) was reported to induce IFN-alpha/beta and to up-regulate MHC class II proteins. In an attempt to resolve this paradox, we examined the surface expression of MHC class I and class II proteins in MV-infected peripheral monocytes in the presence and absence of IFN-alpha/beta. Infection of purified monocytes with Edmonston B MV resulted in an apparent increase in cell surface expression of HLA-A, -B, and -C class I proteins, but it had no effect on the expression of HLA-DR class II proteins. MV-infected purified monocytes expressed IFN-alpha/beta, but no measurable IFN-gamma expression was detected in supernatant fluids. Class II protein expression could be enhanced by coculture of purified monocytes with uninfected peripheral blood mononuclear cell (PBMC) supernatant. MV infection of PBMCs also did not affect expression of class II proteins, but the expression of HLA-A, -B, and -C class I proteins was increased two- to threefold in most donor cells. A direct role for IFN-alpha/beta suppression of MHC class II protein expression was not evident in monocytes since MV suppressed class II protein expression in the absence of IFN-alpha/beta. Taken together, these data suggest that MV interferes with the expression of peptide-loaded class II complexes, an effect that may potentially alter CD4(+)-T-cell proliferation and the cell-mediated immune responses that they help to regulate.