Living with metastatic breast cancer (LIMBER): experiences, quality of life, gaps in information, care and support of patients in the UK.

PURPOSE: To determine the experiences, information, support needs and quality of life of women in the UK living with metastatic breast cancer (MBC) to provide content for educational materials. METHODS: An online survey, hosted for 3 months on a UK MBC charity website, comprised sections covering issues such as communication about MBC treatment and management, helpful and less helpful things that healthcare professionals, family and friends did or said and completion of the Patient Roles and Responsibilities Scale (PRRS). RESULTS: A total of 143 patients participated; 48/143(33%) presented de novo; 54/143(38%) had been living with MBC > 2 years. PRRS analysis revealed that MBC imposed a serious impact upon most respondents' own caring abilities and social lives. A majority 98/139 (71%) wished they had known more about MBC before their diagnosis; 63/134(47%) indicated that they still did not fully understand their illness; merely 78/139(56%) had access to a specialist nurse and only 69/135(51%) had been offered any additional support. Respondents reported little consideration given to their lifestyle/culture during consultations and inconsistent information, support services, continuity of care or access to clinical trials. They commented upon things health care professionals/friends and family did or said that were useful and cited other behaviours that were especially unhelpful. CONCLUSIONS: MBC exerted a deleterious impact upon patients' activities of daily living which were exacerbated in part by significant gaps in support, communication and information. IMPLICATIONS FOR CANCER SURVIVORS: LIMBER results are informing the content of educational materials currently being developed for patients' formal and informal carers.

A structured review of quality of life in advanced and high-risk cutaneous squamous cell carcinoma shows the need for more studies and better measures.

Background: Cutaneous squamous cell carcinoma (cSCC) accounts for nearly a quarter of non-melanoma skin cancers. Studies reporting Quality of Life (QoL) in this group focus on early stage disease. A small proportion of cSCC patients have high-risk or advanced disease, with potentially significant QoL impacts, yet are largely overlooked. Aims: This structured review appraises measures and published QoL outcomes in this group. Materials & Methods: We conducted searches in MEDLINE, EMBASE, CINAHLplus and PsycInfo in June 2020 (updated in October) to identify publications specifically reporting QoL outcomes in this cohort. Returns were reviewed against a strict set of eligibility criteria. Results: We identified seven publications for inclusion; three relating to high-risk cSCC, three to metastatic disease and one to unresectable disease. Publications were appraised for quality using the Mixed Methods Appraisal Tool. Only one fulfilled more than two of the five quality criteria. Studies employed a range of patient reported outcome measures to assess QoL, both generic and disease specific. Discussion: All studies with multiple time-points reported stable or improving QoL, however extrapolation of these findings to the cSCC population is not warranted due to study limitations including mixed populations, incomplete data sets or single measurements. We set out to review the QoL literature for high-risk and advanced cSCC and found a small and disparate body of evidence. Studies varied significantly in terms of study population, design and quality. While the identified studies suggested stable or improving QoL, we question the choice of measures used and highlight the need for further work in this area. Conclusion: While there are some published reports about quality of life for patients with early stage cutaneous squamous cell carcinoma, these impacts for the high-risk or advanced cohort are largely unexplored. We conducted a structured review of published measures and outcomes used in this cohort and found a demonstrable need for further, targeted, exploration of patient needs in this area.

Do drugs offering only PFS maintain quality of life sufficiently from a patient's perspective? Results from AVALPROFS (Assessing the 'VALue' to patients of PROgression Free Survival) study.

PURPOSE: Trials of novel drugs used in advanced disease often show only progression-free survival or modest overall survival benefits. Hypothetical studies suggest that stabilisation of metastatic disease and/or symptom burden are worth treatment-related side effects. We examined this premise contemporaneously using qualitative and quantitative methods. METHODS: Patients with metastatic cancers expected to live > 6 months and prescribed drugs aimed at cancer control were interviewed: at baseline, at 6 weeks, at progression, and if treatment was stopped for toxicity. They also completed Functional Assessment of Cancer Therapy (FACT-G) plus Anti-Angiogenesis (AA) subscale questionnaires at baseline then monthly for 6 months. RESULTS: Ninety out of 120 (75%) eligible patients participated: 41 (45%) remained on study for 6 months, 36 progressed or died, 4 had treatment breaks, and 9 withdrew due to toxicity. By 6 weeks, 66/69 (96%) patients were experiencing side effects which impacted their activities. Low QoL scores at baseline did not predict a higher risk of death or dropout. At 6-week interviews, as the side effect severity increased, patients were significantly less inclined to view the benefit of cancer control as worthwhile (X2 = 50.7, P < 0.001). Emotional well-being initially improved from baseline by 10 weeks, then gradually returned to baseline levels. CONCLUSION: Maintaining QoL is vital to most patients with advanced cancer so minimising treatment-related side effects is essential. As side effect severity increased, drugs that controlled cancer for short periods were not viewed as worthwhile. Patients need to have the therapeutic aims of further anti-cancer treatment explained honestly and sensitively.

Therapeutic aims of drugs offering only progression-free survival are misunderstood by patients, and oncologists may be overly optimistic about likely benefits.

PURPOSE: The use of novel and often expensive drugs offering limited survival benefit in advanced disease is controversial. Treatment recommendations are influenced by patient characteristics and trial data showing overall response rates (ORR), progression-free survival (PFS) and overall survival (OS). PFS is frequently the primary outcome in licencing studies. PATIENTS AND METHODS: As part of a longitudinal study Assessing the 'VALue' to patients of PROgression Free Survival (AVALPROFS), oncologists completed checklists at baseline following consultations with patients. Questions probed perceived clinical benefits of the drugs to populations in general. Patients completed study-specific interview schedules at baseline, 6 weeks into treatment, and at withdrawal due to toxicity or progression. Patients also completed tumour- and treatment-specific quality of life questionnaires monthly for their time in the study. Only baseline results are reported here. RESULTS: Thirty-two UK oncologists discussed management options with 90 patients with heterogeneous advanced cancers. Oncologists' estimates of medical benefit in general from treatment varied between 10 and 80 %. They expected 46/90 (51 %) of their patients to derive some clinical benefit from the prescribed treatment but were either unsure or expected none for 44/90 (49 %). Predictions of life expectancy were variable but 62 % (56/90) of patients were expected to survive longer with treatment. A majority of patients 51/90 (57 %) had 'no idea' or were 'unclear' what PFS meant and 45/90 (50 %) thought extension of life was the primary therapeutic aim of treatment. CONCLUSION: Discussions between doctors and patients with metastatic disease about future management plans and likely therapeutic gains are challenging. Factors influencing decisions about putative benefits of novel drugs are often applied inconsistently can be overly optimistic and may even contradict published data.

A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer.

The neuropsychological performance of 85 women with early stage breast cancer scheduled for chemotherapy, 43 women scheduled for endocrine therapy and/or radiotherapy and 49 healthy control subjects was assessed at baseline (T1), postchemotherapy (or 6 months) (T2) and at 18 months (T3). Repeated measures analysis found no significant interactions or main effect of group after controlling for age and intelligence. Using a calculation to examine performance at an individual level, reliable decline on multiple tasks was seen in 20% of chemotherapy patients, 26% of nonchemotherapy patients and 18% of controls at T2 (18%, 14 and 11%, respectively, at T3). Patients who had experienced a treatment-induced menopause were more likely to show reliable decline on multiple measures at T2 (OR=2.6, 95% confidence interval (CI) 0.823-8.266 P=0.086). Psychological distress, quality of life measures and self-reported cognitive failures did not impact on objective tests of cognitive function, but were significantly associated with each other. The results show that a few women experienced objective measurable change in their concentration and memory following standard adjuvant therapy, but the majority were either unaffected or even improve over time.

The effects of adjuvant chemotherapy on cognition in women with breast cancer--preliminary results of an observational longitudinal study.

Several studies have reported that chemotherapy-treated patients have impaired cognition function relative to control groups. We are conducting a longitudinal study with cognitive assessments at baseline, 6 and 18 months. A planned preliminary analysis of data from 50 chemotherapy patients and 43 healthy controls at baseline and post-treatment found a significant group by time interaction on three measures of verbal and working memory. Chemotherapy patients were more likely to show cognitive decline than controls (OR 2.25). Patients were significantly more likely to have GHQ(12) scores indicative of possible psychological morbidity and showed significant increases in endocrine symptoms and fatigue post-treatment however neither GHQ(12) nor quality-of-life variables were related to cognitive performance.

The effects of oestrogens and anti-oestrogens on cognition.

Recent research suggests that oestrogen may play an important role in cognition. Epidemiological and experimental studies of hormone replacement therapy in post-menopausal women suggest that oestrogen may be important to verbal memory in particular, as well as other cognitive functions such as attention and processing speed. Some studies have also suggested that HRT may have a beneficial effect for Alzheimer's disease, both in the prevention or delay of onset and that it is also of therapeutic benefit to patients in whom the disease is established. The use of selective oestrogen receptor modulators (SERMs) and other hormonal therapies for the treatment of breast cancer is common, yet few studies have examined the possible cognitive effects of this form of treatment. Several studies have shown cognitive decline in women receiving treatment for breast cancer, but the focus has been on the effects of chemotherapy. Further confusion has resulted from the diverse methodologies used in the existing literature. A pilot study to develop a suitable cognitive battery of tests for the evaluation of cognitive function in women receiving hormonal therapy for the treatment or prevention of breast cancer is introduced.

Possible autocrine growth stimulation of cholesteatoma epithelium by transforming growth factor alpha.

INTRODUCTION: Transforming growth factor alpha (TGF-alpha) is known to be produced by normal human keratinocytes and to stimulate their proliferation. The squamous epithelium of middle ear cholesteatoma is believed to exhibit hyperproliferative characteristics. This study was undertaken to determine if growth factors can be identified in cholesteatoma. MATERIALS AND METHODS: Cholesteatoma samples (n = 6) and retroauricular skin (n = 9) were obtained during surgery. Monoclonal antibody against epidermal growth factor (EGF) and TGF-alpha were evaluated in these specimens using immunohistochemical techniques. RESULTS: Epidermal growth factor receptor (EGF-R) was highly expressed in the basal layer of the epidermis, hair follicles, eccrine sweat glands, and the capillary system of normal skin. In the majority of cholesteatoma samples, expression of EGF-R was not confined to the basal layer but persisted in suprabasal cells of the stratum spinosum and stratum granulosum. In two cases, heterogenous standing was found in different parts of the same cryosection. Staining for TGF-alpha was consistently stronger in cholesteatoma than in normal skin, and encompassed all epithelial cell layers. Immune cells infiltrating the stroma of cholesteatoma stained positively for TGF-alpha. CONCLUSION: These data are consistent with autocrine stimulation of the squamous epithelium of cholesteatoma by TGF-alpha contributing to its unrestrained growth in the middle ear cavity.