Return-to-Work Coordinators' Perceptions of Their Roles Relative to Workers: A Discourse Analysis.

PURPOSE: This paper describes how Canadian Return to Work coordinators (RTWC) framed their job roles relative to workers in ways that went beyond the usual professional norms of helping worker recovery. METHODS: In-depth interviews were conducted with 47 RTWCs across Canada in 2018-2019. We used critical discourse analysis to analyze the way coordinators viewed workers in the complex, multi-stakeholder system of RTW. RESULTS: We identified four ways that RTWCs positioned themselves relative to workers: as trust builders, experts, detectives and motivators. These roles reflected RTWCs position within the system; however, their discourse also contributed to the construction of a moral hierarchy that valued worker motivation and framed some workers as attempting to exploit the RTW system. CONCLUSIONS: RTWCs' positions of power in the coordination process warrant further investigation of how they exercise judgement and discretion, particularly when the process depends on their ability to weigh evidence and manage cases in what might be seen as an objective and fair manner.

The effect of size and sex ratio experiences on reproductive competition in Nicrophorus vespilloides burying beetles in the wild.

Male parents face a choice: should they invest more in caring for offspring or in attempting to mate with other females? The most profitable course depends on the intensity of competition for mates, which is likely to vary with the population sex ratio. However, the balance of pay-offs may vary among individual males depending on their competitive prowess or attractiveness. We tested the prediction that sex ratio and size of the resource holding male provide cues regarding the level of mating competition prior to breeding and therefore influence the duration of a male's biparental caring in association with a female. Male burying beetles, Nicrophorus vespilloides were reared, post-eclosion, in groups that differed in sex ratio. Experimental males were subsequently translocated to the wild, provided with a breeding resource (carcass) and filmed. We found no evidence that sex ratio cues prior to breeding affected future parental care behaviour but males that experienced male-biased sex ratios took longer to attract wild mating partners. Smaller males attracted a higher proportion of females than did larger males, securing significantly more monogamous breeding associations as a result. Smaller males thus avoided competitive male-male encounters more often than larger males. This has potential benefits for their female partners who avoid both intrasexual competition and direct costs of higher mating frequency associated with competing males.

Do female Nicrophorus vespilloides reduce direct costs by choosing males that mate less frequently?

Sexual conflict occurs when selection to maximize fitness in one sex does so at the expense of the other sex. In the burying beetle Nicrophorus vespilloides, repeated mating provides assurance of paternity at a direct cost to female reproductive productivity. To reduce this cost, females could choose males with low repeated mating rates or smaller, servile males. We tested this by offering females a dichotomous choice between males from lines selected for high or low mating rate. Each female was then allocated her preferred or non-preferred male to breed. Females showed no preference for males based on whether they came from lines selected for high or low mating rates. Pairs containing males from high mating rate lines copulated more often than those with low line males but there was a negative relationship between female size and number of times she mated with a non-preferred male. When females bred with their preferred male the number of offspring reared increased with female size but there was no such increase when breeding with non-preferred males. Females thus benefited from being choosy, but this was not directly attributable to avoidance of costly male repeated mating.

Learning from the QUEST multicentre feasibility randomization trials in breast reconstruction after mastectomy.

BACKGROUND: Breast reconstruction aims to improve health-related quality of life after mastectomy. However, evidence guiding patients and surgeons in shared decision-making concerning the optimal type or timing of surgery is lacking. METHODS: QUEST comprised two parallel feasibility phase III randomized multicentre trials to assess the impact of the type and timing of latissimus dorsi breast reconstruction on health-related quality of life when postmastectomy radiotherapy is unlikely (QUEST A) or highly probable (QUEST B). The primary endpoint for the feasibility phase was the proportion of women who accepted randomization, and it would be considered feasible if patient acceptability rates exceeded 25 per cent of women approached. A companion QUEST Perspectives Study (QPS) of patients (both accepting and declining trial participation) and healthcare professionals assessed trial acceptability. RESULTS: The QUEST trials opened in 15 UK centres. After 18 months of recruitment, 17 patients were randomized to QUEST A and eight to QUEST B, with overall acceptance rates of 19 per cent (17 of 88) and 22 per cent (8 of 36) respectively. The QPS recruited 56 patients and 51 healthcare professionals. Patient preference was the predominant reason for declining trial entry, given by 47 (53 per cent) of the 88 patients approached for QUEST A and 22 (61 per cent) of the 36 approached for QUEST B. Both trials closed to recruitment in December 2012, acknowledging the challenges of achieving satisfactory patient accrual. CONCLUSION: Despite extensive efforts to overcome recruitment barriers, it was not feasible to reach timely recruitment targets within a feasibility study. Patient preferences for breast reconstruction types and timings were common, rendering patients unwilling to enter the trial.

Male burying beetles extend, not reduce, parental care duration when reproductive competition is high.

Male parents spend less time caring than females in many species with biparental care. The traditional explanation for this pattern is that males have lower confidence of parentage, so they desert earlier in favour of pursuing other mating opportunities. However, one recent alternative hypothesis is that prolonged male parental care might also evolve if staying to care actively improves paternity. If this is the case, an increase in reproductive competition should be associated with increased paternal care. To test this prediction, we manipulated the level of reproductive competition experienced by burying beetles, Nicrophorus vespilloides (Herbst, 1783). We found that caregiving males stayed for longer and mated more frequently with their partner when reproductive competition was greater. Reproductive productivity did not increase when males extended care. Our findings provide support for the increased paternity hypothesis. Extended duration of parental care may be a male tactic both protecting investment (in the current brood) and maximizing paternity (in subsequent brood(s) via female stored sperm) even if this fails to maximize current reproductive productivity and creates conflict of interest with their mate via costs associated with increased mating frequency.

Menopausal symptoms and bone health in women undertaking risk reducing bilateral salpingo-oophorectomy: significant bone health issues in those not taking HRT.

BACKGROUND: Women at high ovarian cancer risk, especially those with mutations in BRCA1/BRCA2, are encouraged to undergo bilateral risk-reducing salpingo-oophorectomy (BRRSPO) prior to the natural menopause. The decision to use HRT to cover the period of oestrogen deprivation up to 50 years of age is difficult because of balancing the considerations of breast cancer risk, bone and cardiovascular health. METHODS: We reviewed by questionnaire 289 women after BRRSPO aged ≤48 years because of high ovarian cancer risk; 212 (73%) of women responded. RESULTS: Previous HRT users (n=67) had significantly worse endocrine symptom scores than 67 current users (P=0.006). A total of 123 (58%) of women had ≥24 months of oestrogen deprivation <50 years with 78 (37%) never taking HRT. Bone density (DXA) evaluations were available on 119 (56%) women: bone loss with a T score of ≤-1.0 was present in 5 out of 31 (16%) women with no period of oestrogen deprivation <50 years compared with 37 out of 78 (47%) of those with ≥24 months of oestrogen deprivation (P=0.03). INTERPRETATION: Women undergoing BRRSPO <50 years should be counselled concerning the risks/benefits of HRT, taking into consideration the benefits on symptoms, bone health and cardiovascular health, and that the risks of breast cancer from oestrogen-only HRT appear to be relatively small.

Risk reducing mastectomy: outcomes in 10 European centres.

BACKGROUND: Increasingly women at high risk of breast cancer are opting for risk reducing surgery. The aim of this study was to assess the effectiveness of this approach in women at high risk in both carriers and non-carriers of BRCA1/2. METHODS: Data from 10 European centres that offer a genetic counselling and screening service to women at risk were obtained prospectively from 1995. Breast cancer risks were estimated from life tables and a control group of women at risk who did not undergo surgery. RESULTS: The combined centres have data on 550 women who have undergone risk reducing mastectomy with greater than 3334 women years of follow-up. Operations were carried out on women with lifetime risks of 25-80%, with an average expected incidence rate of 1% per year. No breast cancers have occurred in this cohort in the "at risk" unaffected breast, whereas >34 would have been expected. A high rate (2-3.6%) of occult disease was identified in the at risk breast at the time of surgery. INTERPRETATION: We conclude that risk reducing surgery is highly effective.

The UK national breast cancer screening programme for survivors of Hodgkin lymphoma detects breast cancer at an early stage.

BACKGROUND: Supradiaphragmatic radiotherapy (SRT) to treat Hodgkin's lymphoma (HL) at a young age increases the risk of breast cancer (BC). A national notification risk assessment and screening programme (NRASP) for women who were treated with SRT before the age of 36 years was instituted in the United Kingdom in 2003. In this study, we report the implementation and screening results from the largest English Cancer Network. METHODS: A total of 417 eligible women were identified through cancer registry/hospital databases and from follow-up (FU) clinics. Screening results were collated retrospectively, and registry searches were used to capture BC cases. RESULTS: Of the 417 women invited for clinical review, 243 (58%) attended. Of these 417 women, 23 (5.5%) have been diagnosed with BC, a standardised incidence ratio of 2.9 compared with the age-matched general population. Of five invasive BCs diagnosed within the NRASP, none involved axillary lymph nodes compared with 7 of 13 (54%) diagnosed outside the programme (P<0.10). The mean latency for BC cases was 19.5+/-8.35 years and the mean FU duration for those unaffected by BC was 14.6+/-9.11 years (P<0.01), suggesting that those unaffected by BC remain at high risk. Recall and negative biopsy rates were acceptable (10.5 and 0.8%, respectively). CONCLUSIONS: The NRASP appears to detect BC at an early stage with acceptable biopsy rates, although numbers are small. Determination of NRASP results on a national basis is required for the accurate evaluation of screening efficacy in women previously treated with SRT.

The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for early breast cancer delivers 50 Gy in 25 fractions of 2.0 Gy over 5 weeks, but there is a long history of non-standard regimens delivering a lower total dose using fewer, larger fractions (hypofractionation). We aimed to test the benefits of radiotherapy schedules using fraction sizes larger than 2.0 Gy in terms of local-regional tumour control, normal tissue responses, quality of life, and economic consequences in women prescribed post-operative radiotherapy. METHODS: Between 1999 and 2001, 2215 women with early breast cancer (pT1-3a pN0-1 M0) at 23 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy over 5 weeks or 40 Gy in 15 fractions of 2.67 Gy over 3 weeks. Women were eligible for the trial if they were aged over 18 years, did not have an immediate reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 1105 women were assigned to the 50 Gy group and 1110 to the 40 Gy group. After a median follow up of 6.0 years (IQR 5.0-6.2) the rate of local-regional tumour relapse at 5 years was 2.2% (95% CI 1.3-3.1) in the 40 Gy group and 3.3% (95% CI 2.2 to 4.5) in the 50 Gy group, representing an absolute difference of -0.7% (95% CI -1.7% to 0.9%)--ie, the absolute difference in local-regional relapse could be up to 1.7% better and at most 1% worse after 40 Gy than after 50 Gy. Photographic and patient self-assessments indicated lower rates of late adverse effects after 40 Gy than after 50 Gy. INTERPRETATION: A radiation schedule delivering 40 Gy in 15 fractions seems to offer rates of local-regional tumour relapse and late adverse effects at least as favourable as the standard schedule of 50 Gy in 25 fractions.

Comparison of proactive and usual approaches to offering predictive testing for BRCA1/2 mutations in unaffected relatives.

There have been few studies addressing uptake of predictive testing for BRCA1/2, only one comparing a proactive with usual family networking approach to dissemination. We report uptake of predictive genetic testing after directly offering BRCA1 presymptomatic genetic testing to 100 individuals in two generations of 5 large BRCA1 families compared with service testing of 196 families since that time. Uptake was significantly higher in the first generation (group 1), who were directly offered testing, and much higher in females. Seventy-four percent of unaffected women in the first generation proceeded to testing, 42% of men. This decreased to 44% of women in the second generation (group 2) and 9% males (p = 0.0003). Uptake in unaffected individuals in the final group (group 3) with no proactive approach was significantly lower than that in the first group. Overall uptake after 10 years was 56% (95% confidence interval, CI, 50-62%) for group 1 and 36% (95% CI 34.3-37.7%) for 1084 group 3 individuals (p = 0.0003). Among women, uptake was 74% (95% CI 67-81%) in group 1 at 10 years compared with 51.5% (95% CI 49-54%) in 552 group 3 women (p = 0.023). In men, uptake was 42% (95% CI 33-52%) in group 1 and 21.1% (95% CI 18.1-23.1%) among 532 men in group 3 (p = 0.0098). Although these results are not from a randomized trial, they show particularly among men a substantially higher uptake of genetic services with a direct approach. Importance should be given to more proactive approaches to ensure that men in BRCA1/2-positive families receive the appropriate information.

Health-related quality of life assessment after breast reconstruction.

BACKGROUND: Health-related quality of life (HRQL) is an important outcome following breast reconstruction. This study evaluated current methods of HRQL assessment in patients undergoing latissimus dorsi breast reconstruction, hypothesizing that early surgical morbidity would be reflected by poorer HRQL scores. METHODS: Patients completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and breast module (QLQ-BR23), the Functional Assessment of Cancer Therapy (FACT) general measure, and breast module and arm subscale (FACT-B + 4), and the Body Image Scale and Hospital Anxiety and Depression Scale (HADS) 3 months after surgery. They also reported additional HRQL problems not included in the questionnaires. HRQL scores were compared between patients with and without early surgical morbidity. RESULTS: Sixty women completed the questionnaires, of whom 25 (42 per cent) experienced complications. All EORTC and FACT subscale and HADS scores were similar in patients with or without morbidity. Women with complications were twice as likely to report feeling less feminine and dissatisfied with the appearance of their scar than those without problems. Thirty-two women (53 per cent) complained of problems not covered by the questionnaires, most commonly donor-site morbidity. CONCLUSION: Existing HRQL instruments are not sufficiently sensitive to detect clinically relevant problems following breast reconstruction.

The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses (fractions). However, a lower total dose delivered in fewer, larger fractions (hypofractionation) is hypothesised to be at least as safe and effective as the standard treatment. We tested two dose levels of a 13-fraction schedule against the standard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size. METHODS: Between 1998 and 2002, 2236 women with early breast cancer (pT1-3a pN0-1 M0) at 17 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy versus 41.6 Gy or 39 Gy in 13 fractions of 3.2 Gy or 3.0 Gy over 5 weeks. Women were eligible if they were aged over 18 years, did not have an immediate surgical reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 749 women were assigned to the 50 Gy group, 750 to the 41.6 Gy group, and 737 to the 39 Gy group. After a median follow up of 5.1 years (IQR 4.4-6.0) the rate of local-regional tumour relapse at 5 years was 3.6% (95% CI 2.2-5.1) after 50 Gy, 3.5% (95% CI 2.1-4.3) after 41.6 Gy, and 5.2% (95% CI 3.5-6.9) after 39 Gy. The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0.2% (95% CI -1.3% to 2.6%) after 41.6 Gy and 0.9% (95% CI -0.8% to 3.7%) after 39 Gy. Photographic and patient self-assessments suggested lower rates of late adverse effects after 39 Gy than with 50 Gy, with an HR for late change in breast appearance (photographic) of 0.69 (95% CI 0.52-0.91, p=0.01). From a planned meta-analysis with the pilot trial, the adjusted estimates of alpha/beta value for tumour control was 4.6 Gy (95% CI 1.1-8.1) and for late change in breast appearance (photographic) was 3.4 Gy (95% CI 2.3-4.5). INTERPRETATION: The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size. 41.6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractions in terms of local-regional tumour control and late normal tissue effects, a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international standard fractionation schedule of 50 Gy in 25 fractions.

Women's Free-text Comments on their Quality of Life: An Exploratory Analysis from the UK Standardisation of Breast Radiotherapy (START) Trials for Early Breast Cancer.

AIMS: Exploratory analysis of patients' unsolicited written comments in the first 2 years of the Standardisation of Breast Radiotherapy (START) trial quality of life study highlighted a potential effect of non-treatment-related problems on the ratings and interpretation of patient self-reported questionnaires. At 5 years of follow-up all eligible subjects were invited to write comments to further explore these findings. MATERIALS AND METHODS: Using inductive qualitative methods informed by the exploratory analysis, comments were allocated to relevant themes. Key patient-reported outcome measures (PROMs), clinical and demographic factors were collated for patients who did and did not comment at 5 years and comparisons between the groups explored. RESULTS: Of 2208 women completing baseline PROMs, 482 proffered comments from 0 to 24 months, forming nine distinct themes, including chronic conditions, life events and psychosocial concerns. At 5 years, 1041/1727 (60.3%) women contributed comments, of whom 500 randomly selected participants formed the sample for analysis. Findings revealed comorbidity, impaired physical functioning and psychosocial problems as key themes, with prevalent adverse effects from local and systemic treatments. Eight new themes emerged at 5 years, including ageing, concerns about future cancer and positive aspects of care. Women commenting were better educated, slightly older and more likely to have had chemotherapy compared with non-commenters. They had significantly worse PROM scores for global health and key quality of life domains relevant to the difficulties they revealed. CONCLUSIONS: Difficult personal circumstances and other health concerns affected many women's PROM ratings at 5 years of follow-up, in addition to ongoing cancer treatment effects. Greater attention to multiple sources of distress and adversity could facilitate personalised care and aid interpretation of PROMs.

Do Patient-reported Outcome Measures Agree with Clinical and Photographic Assessments of Normal Tissue Effects after Breast Radiotherapy? The Experience of the Standardisation of Breast Radiotherapy (START) Trials in Early Breast Cancer.

AIMS: In radiotherapy trials, normal tissue effects (NTE) are important end points and it is pertinent to ask whether patient-reported outcome measures (PROMs) could replace clinical and/or photographic assessments. Data from the Standardisation of Breast Radiotherapy (START) trials are examined. MATERIALS AND METHODS: NTEs in the treated breast were recorded by (i) annual clinical assessments, (ii) photographs at 2 and 5 years, (iii) PROMs at 6 months, 1, 2 and 5 years after radiotherapy. Hazard ratios for the radiotherapy schedules were compared. Measures of agreement of assessments at 2 and 5 years tested concordance. RESULTS: PROMs were available at 2 and/or 5 years for 1939 women, of whom 1870 had clinical and 1444 had photographic assessments. All methods were sensitive to the dose difference between schedules. Patients reported a higher prevalence for all NTE end points than clinicians or photographs (P < 0.001 for most NTEs). Concordance was generally poor; weighted kappa at 2 years ranged from 0.05 (telangiectasia) to 0.21 (shrinkage and oedema). The percentage agreement was lowest between PROMs and photographic assessments of change in breast appearance (38%). CONCLUSIONS: All three methods produced similar conclusions for the comparison of trial schedules, despite low concordance between the methods on an individual patient basis. Careful consideration should be given to the different contributions of the measures of NTE in future radiotherapy trials.

Epstein-Barr virus latent membrane protein does not inhibit differentiation and induces tumorigenicity of human epithelial cells.

Latent membrane protein (LMP) is a latent Epstein-Barr virus (EBV) protein expressed in the EBV associated malignancy, nasopharyngeal carcinoma (NPC). Properties ascribed to this protein include inhibition of epithelial cell differentiation and deregulation of epithelial cellular gene expression, and are believed to contribute to the development of NPC. Studies to evaluate the oncogenic potential of LMP in epithelial cells have not been conclusive. We carried out studies to determine the tumorigenic activity of LMP in two human epithelial cell lines, SCC12F and HaCaT; while SCC12F LMP transfectants were non-tumorigenic in severe combined immunodeficient mice, HaCaT LMP transfectants were strongly oncogenic. The tumours produced were well differentiated, keratinising squamous cell carcinomas suggesting that LMP does not inhibit epithelial cell differentiation which conflicts with a previous report by Dawson et al. (1990). To resolve this discrepancy we examined the ability of HaCaT and SCC12F LMP transfectants to differentiate in a suspension culture assay. Both lines were able to differentiate to a similar extent as parental lines and control transfectants. Our results indicate that LMP is strongly oncogenic in human epithelial cells but that inhibition of differentiation is not necessarily a mechanism by which LMP contributes to the pathogenesis of NPC.

Depression in patients with lung cancer: prevalence and risk factors derived from quality-of-life data.

PURPOSE: To evaluate self-reported depression rates in patients with inoperable lung cancer and to explore demographic, clinical, and quality-of-life (QOL) factors associated with depression and thus identify patients at risk. PATIENTS AND METHODS: Nine hundred eighty-seven patients from three palliative treatment trials conducted by the Medical Research Council Lung Cancer Working Party formed the study sample. 526 patients (53%) had poor prognosis small-cell lung cancer (SCLC) and 461 patients (47%) had good prognosis non-small-cell lung cancer (NSCLC). Hospital Anxiety and Depression Scale data and QOL items from the Rotterdam Symptom Checklist were analyzed, together with relevant demographic and clinical factors. RESULTS: Depression was self-rated in 322 patients (33%) before treatment and persisted in more than 50% of patients. SCLC patients had a three-fold greater prevalence of case depression than those with NSCLC (25% v 9%; P <.0001). An increased rate for women was found for good performance status (PS) patients (PS of 0 or 1) but the sex difference reduced for poor PS patients (PS of 3 or 4) because of increased depression rates for men (chi(2) for trend, P <.0001). Multivariate analysis showed that functional impairment was the most important risk factor; depression increased by 41% for each increment on the impairment scale. Pretreatment physical symptom burden, fatigue, and clinician-rated PS were also independent predictors, but cell type was not. CONCLUSION: Depression is common and persistent in lung cancer patients, especially those with more severe symptoms or functional limitations. Psychologic screening and appropriate intervention is an essential part of palliative care.

Improving survival without reducing quality of life in small-cell lung cancer patients by increasing the dose-intensity of chemotherapy with granulocyte colony-stimulating factor support: results of a British Medical Research Council Multicenter Randomized Trial. Medical Research Council Lung Cancer Working Party.

PURPOSE: The treatment of small-cell lung cancer patients with good performance status aims to improve survival. Dose-intensification could be a way to achieve improved survival but can be limited by neutropenia and thrombocytopenia. Preliminary, nonrandomized feasibility studies showed that doxorubicin, cyclophosphamide, and etoposide (ACE) could be given every 2 (instead of the usual 3) weeks with granulocyte colony-stimulating factor (G-CSF) (lenograstim; Chugai-Rh¿one-Poulenc, Tokyo, Japan) support. The present multicenter randomized trial was designed to examine whether such dose-intensification improves survival while maintaining acceptable toxicity levels. PATIENTS AND METHODS: All patients were randomized to receive six cycles of ACE either every 3 weeks (control [C] group) or every 2 weeks with G-CSF (G group). The standard dose-intensity of ACE was increased by 50% in group G. RESULTS: Four hundred and three patients (G group: n = 201; C group: n = 202) were randomized. The received dose-intensity was 34% higher in the G group than in the C group. Complete response rates were 40% for the G group and 28% for the C group (P =.02), and overall rates were 78% for the G group and 79% for the C group. Survival was longer in the G group (hazard ratio = 0.80; 95% confidence interval, 0.65 to 0.99; P =.04), survival rates for the G and C groups being 47% and 39% at 12 months and 13% and 8% at 24 months, respectively. Metastasis-free survival, nonhematologic toxicity, and quality of life were similar in the two groups. In the G group, there was less neutropenia but more thrombocytopenia and more frequent blood and platelet transfusions. CONCLUSION: Increasing the dose-intensity of ACE with G-CSF support improved survival while maintaining acceptable toxicity.

The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: first results from a three-country field study.

PURPOSE: To construct a breast cancer-specific quality-of-life questionnaire (QLQ) module to be used in conjunction with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and to test its reliability and validity cross-culturally. PATIENTS AND METHODS: Module construction took place after the EORTC guidelines for module development. The module--the QLQ-BR23--consists of 23 items covering symptoms and side effects related to different treatment modalities, body image, sexuality, and future perspective. This module was tested in 170 Dutch, 168 Spanish, and 158 American cancer patients at two points in time. The timing for the Dutch and Spanish patients was before and during treatment with radiotherapy or chemotherapy. For the American patients, the questionnaire was administered at admission at the breast clinic and 3 months after the first assessment. RESULTS: Multitrait scaling analysis confirmed the hypothesized structure of four of the five scales. Cronbach's alpha coefficients were, in general, lowest in Spain (range; .46 to .94) and highest in the United States (range; .70 to .91). On the basis of known-groups comparisons, selective scales distinguished clearly between patients differing in disease stage, previous surgery, performance status, and treatment modality, according to expectation. Additionally, selective scales detected change over time as a function of changes in performance status and treatment-induced change. CONCLUSION: These results lend support to the clinical and cross-cultural validity of the QLQ-BR23 as a supplementary questionnaire for assessing specific quality-of-life issues relevant to patients with breast cancer.

Surgical decisions made by 158 women with hereditary breast cancer aged <50 years.

AIM: To establish the uptake of contralateral risk reducing mastectomy in women informed of their risks and options at time of diagnosis of their primary unilateral breast cancer. METHODS: We have assessed the surgical choices of 70 women diagnosed with breast cancer <50 years as part of a family history surveillance program and fully informed about their contralateral risks and surgical options. We have compared this to women from other surgical clinics who were subsequently found to harbour a pathogenic BRCA1/2 mutation. RESULTS: Sixty-five percent (13/20) of BRCA1/2 mutation carriers and 59% (n=20/34) of those at the highest level of risk pre-diagnosis (33+% lifetime risk) opted for contra-lateral mastectomy in the study sample. In contrast only 10% (n=9/88) women identified as mutation carriers from other clinics opted for such surgery. CONCLUSIONS: We would suggest that women with a significant family history and therefore a high contra-lateral breast cancer risk, should have these risks and management options discussed at the time of diagnosis of breast cancer.

United Kingdom Cancer Research Campaign approach to quality-of-life research in cancer clinical trials.

Clinical trials of new anticancer therapies form an important part of the research activity of the Cancer Research Campaign (United Kingdom), and quality-of-life (QOL) end points are being increasingly used in the evaluation of new treatment approaches. The Campaign has a unique policy of supporting a broad range of scientific and clinical research, including psychosocial studies, and thus QOL research is generated in a variety of clinical settings. The focus of interest for the Cancer Research Campaign lies in QOL design and assessment rather than the routine application of QOL protocols. Clinical investigators are free to adopt in individual approach, but the Campaign operates a strict peer-review system in protocol assessment. Some standardization of approach is being achieved through consensus of opinion and wide collaboration, both nationally and internationally.