IMPARTER, Phase 1 of an intervention to improve patients' understanding of gene expression profiling tests in breast cancer.

PURPOSE: To compare participants' knowledge about gene expression profiling (GEP) tests and recurrence risks after reading an information leaflet with that following viewing of an information film. METHODS: Using a randomised cross-over design, at time-point one (T1), women aged 45-75 years without breast cancer either read leaflets or watched information films about Oncotype DX or Prosigna tests. Participants answered nine questions assessing knowledge (maximum score 18). Next-day information in the opposite modality was provided and knowledge re-assessed. Additional questions probed which format was easiest to understand, participants' preferences for film or leaflet and their reasons for these. RESULTS: 120 women participated (60 received OncotypeDX films and leaflets; 60 received the Prosigna versions). T1 mean knowledge scores were higher following film viewing (13.37) compared with that after reading leaflets (9.25) (mean difference 4.1; p < 0.0001; 95% CI 3.2, 5.0). When participants read leaflets first and subsequently viewed films, all increased their scores (mean + 6.08, from T1 of 9.25, p < 0.0001; 95% CI 5.44, 6.72). When films were viewed first, followed by leaflets, (36/60, 60%), participants' scores declined (mean-1.55 from T1 of 13.37, p < 0.001; 95% CI -2.32, -0.78). A majority of participants expressed preferences for the films (88/120, 73.3%) irrespective as to whether they described OncotypeDX or Prosigna. Reasons included the clarity, ease of understanding, visual material and reassuring voice-over. CONCLUSION: Discussions between oncologists and patients about recurrence risk results can be challenging. Information leaflets may aid understanding but often employ complex language. Information films significantly improved knowledge and were preferred by participants.

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.

No man's land: information needs and resources of men with metastatic castrate resistant prostate cancer.

The majority of men treated for prostate cancer will eventually develop castrate-resistant disease (CRPC) with metastases (mCRPC). There are several options for further treatment: chemotherapy, third-line hormone therapy, radium, immunotherapy, and palliation. Current ASCO guidelines for survivors of prostate cancer recommend that an individual's information needs at all stages of disease are assessed and that patients are provided with or referred to the appropriate sources for information and support. Earlier reviews have highlighted the dearth of such services and we wished to see if the situation had improved more recently. Unfortunately, we conclude that there is still a lack of good-quality congruent information easily accessible specifically for men with mCRPC and insufficient data regarding the risks, harms, and benefits of different management plans. More research providing a clear evidence base about treatment consequences using patient reported outcome measures is required.

Adjuvant chemotherapy in elderly women with breast cancer (AChEW): an observational study identifying MDT perceptions and barriers to decision making.

BACKGROUND: As few older women with breast cancer receive adjuvant chemotherapy, we examined the barriers and perceptions of 24 UK NHS multidisciplinary breast cancer teams to offering this treatment to women ≥70 years. PATIENTS AND METHODS: Questionnaires regarding 803 patients with newly diagnosed breast cancer were completed by specialist teams following discussion or outpatient consultation. RESULTS: Of 803 patients, 116 (14%), all <85 years, were offered chemotherapy and 66 (8%) received it. Only 94 of 309 (30%) of women with high-risk disease were offered chemotherapy, and 53 (17%) received it. The most common reasons for not offering chemotherapy were 'other treatments more appropriate' (usually patients with ER-positive tumours) or 'benefits too small' (63% and 54% of patients, respectively). Co-morbidities and frailty were less common reasons but became more frequent with increasing age. Recommendations regarding chemotherapy were made in the absence of documented HER2 and performance status in 29% and 33%, respectively. Treatment offered varied considerably between cancer centres. CONCLUSIONS: National guidelines need development describing the minimally acceptable data for decision making, incorporating objective fitness measures and specific treatment recommendations. Such guidelines will require educational support for implementation but should standardise care and improve chemotherapy uptake in this increasing population of older patients.

Long-term assessment of quality of life in the Intergroup Exemestane Study: 5 years post-randomisation.

BACKGROUND: The Intergroup Exemestane Study (IES) (ISRCTN11883920) demonstrated improved survival for postmenopausal women with ER-positive/unknown primary breast cancer who switched to exemestane after 2-3 years tamoxifen, compared with those continuing on tamoxifen to complete 5 years therapy. This was achieved without detriment to on-treatment quality-of-life (QoL). We report on- and post-treatment QoL impact in IES. METHODS: A total of 582 patients from 8 countries participated in the QoL substudy. Functional Assessment of Cancer Therapy-Breast (FACT-B) and endocrine symptom subscale (ES) were completed at baseline, 3, 6, 9, 12, 18, 24, 30, 36, 48 and 60 months. The primary endpoint was FACT-B Trial Outcome Index (TOI); secondary endpoints included severity of individual endocrine symptoms. RESULTS: Both the groups showed gradual improvement in overall QoL and lessening of total endocrine symptoms post treatment compared with baseline (P<0.002). There was no evidence of any between-group differences in TOI. Vasomotor complaints remained high on treatment. Vaginal discharge was more frequent (P<0.01) with tamoxifen up to 24 months from baseline. In both the groups, post-treatment libido did not recover to baseline levels. CONCLUSION: Clinical benefits of switching to exemestane are accompanied by good overall QoL. Although some symptoms persist, the majority of endocrine symptoms improve after treatment completion.

Clinical benefit in patients with metastatic bone disease: results of a phase 3 study of denosumab versus zoledronic acid.

BACKGROUND: Patients with metastatic bone disease are living longer in the metastatic stage due to improvements in cancer therapy, making strategies to prevent the aggravation of bone disease and its complications, such as skeletal-related events (SREs) and pain, increasingly important. PATIENTS AND RESULTS: In this phase 3 trial in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma, denosumab reduced the risk of radiation to bone by 22% relative to zoledronic acid (P = 0.026), prevented worsening of pain and pain interference (2-point increase in Brief Pain Inventory score; P < 0.05 versus zoledronic acid), and reduced the frequency of a shift from no/weak opioid analgesic use to strong opioids (P < 0.05 versus zoledronic acid at months 3-5). Denosumab delayed the time to moderate-to-severe pain compared with zoledronic acid in patients with mild or no pain at the baseline (P = 0.04), supporting early treatment. Health-related quality-of-life scores were similar in both groups. The number needed to treat to avoid one SRE for denosumab was 3 patient-years versus placebo and 10 patient-years versus zoledronic acid. CONCLUSION: The use of denosumab was associated with better prevention of the complications of metastatic bone disease secondary to solid tumors or multiple myeloma versus zoledronic acid.

Quality of life and patient-reported outcomes in the older breast cancer patient.

As the world population ages, the incidence of cancer will probably also increase as it is a disease predominantly affecting older people. However, those aged 70 years or more have largely been excluded from clinical trials. This review focuses on breast cancer. Increasingly there is recognition that many older breast cancer patients are being undertreated and could and should be offered the same treatments as younger patients. Comprehensive assessment of the quality of any survival benefit from treatments is also needed to ensure that in the future older patients can make fully informed decisions about their treatment options. The aim of this overview is two-fold: first to describe methods by which to assess quality of life; and second to review the recent surgical, radiotherapy, chemotherapy and other studies that include such assessment with older breast cancer patients. Current studies are also outlined, including quality of life assessments, and recommendations are made for future research in this area.

Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial.

BACKGROUND: Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival. METHODS: 4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period. The primary endpoint was disease-free survival; overall survival was a secondary endpoint. Efficacy analyses were intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN11883920. RESULTS: After a median follow-up of 55.7 months (range 0-89.7), 809 events contributing to the analysis of disease-free survival had been reported (354 exemestane, 455 tamoxifen); unadjusted hazard ratio 0.76 (95% CI 0.66-0.88, p=0.0001) in favour of exemestane, absolute benefit 3.3% (95% CI 1.6-4.9) by end of treatment (ie, 2.5 years after randomisation). 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted hazard ratio 0.85 (95% CI 0.71-1.02, p=0.08), 0.83 (0.69-1.00, p=0.05) when 122 patients with oestrogen-receptor-negative disease were excluded. CONCLUSIONS: Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival.

Treatment decision-making in breast cancer: the patient-doctor relationship.

A diagnosis of breast cancer, whether the disease is early or advanced, can be devastating. With this in mind, constructive patient-physician relationships are essential to minimizing disease-related stress and anxiety, as patients undergo treatment and learn to cope with their diagnosis. Good communication skills are vital, and achieve measurable benefits, yet doctors receive very little training in communication. Patients may find it difficult to process large amounts of information, may not understand medical terminology, and can become confused or scared during discussions. They may need time to absorb information, and discuss it with friends and family, before treatment decisions are made. Patient awareness of treatment options is greater than ever, largely because of media exposure and the internet. Consequently, patients' expectations and desire to be involved in treatment choice are increasing, although some patients still prefer to leave decision-making to their doctor. Information about potential side-effects and other treatment burdens is vital, if patients are to make truly informed choices. Knowing in advance what side effects may be encountered, and how to manage them, can also help to improve adherence to treatment, which is necessary for patients to gain the maximum benefit. Side effects that patients find most problematic often differ from those that most concern doctors. Individual patients have different needs and expectations that must be respected, but ensuring that they understand their diagnosis, and the expected benefits and potential risks of treatment, is the key to establishing a good therapeutic relationship and providing the best possible care.

Behavioural interventions and psychological aspects of care during chemotherapy.

Numerous studies have reported the deleterious impact that the side effects of cytotoxic chemotherapy can exert on the quality of life in patients with cancer. Nausea and vomiting consistently feature as the most distressing aspects of cancer therapy. Uncontrolled emesis can cause patients to abandon treatment and the poor public image of chemotherapy may lead others to refuse treatment altogether. Anticipatory nausea and vomiting can also develop in patients and this may persist for many years after successful completion of treatment. There are several behavioural interventions that are effective in ameliorating or preventing these unpleasant side effects. Consequently, psychological support should be provided as an integral part of good patient management, alongside appropriate antiemetic and anxiolytic drugs. As we can identify the characteristics of those patients more at risk from severe emesis and the development of anticipatory problems, there are good arguments for the most effective drug therapy (rather than the cheapest) being given to them prophylactically, together with relaxation techniques.

How do doctors explain randomised clinical trials to their patients?

As part of a larger study designed to improve doctor-patient communication in randomised clinical trials (RCT), we audiotaped the discussions between doctor and patient in which consent was being obtained for a RCT. This paper reports on 82 discussions conducted by 5 clinical oncologists in both District General and University Hospital outpatient departments. When introducing the subject of trials, uncertainty about treatment decisions was expressed by the doctors in the majority of cases (79, 96.3%). This was most often stated in a general sense (78, 95.1%), but some mentioned personal uncertainty (12, 14.6%), an approach which helps to maintain a trusting doctor-patient relationship. The word randomization was mentioned in 51 (62.2%) consultations, although the process itself was usually described implicitly (78, 95.1%), e.g. by telling the patient that they would be allocated either one or other treatment. Analogies were used in 28 (34.1%) cases to describe the randomisation process. In addition, although treatments and side-effects were described frequently, (68, 82.9%) and (72, 87.8%) respectively, information leaflets about the trials were not given to 23 (28%) patients. The study shows that U.K. clinicians adopt individual methods when providing information and eliciting consent to trials.

Attitudes of patients to randomised clinical trials of cancer therapy.

The aim of this study was to test an instrument which might be useful for doctors in explaining the randomisation procedure to an individual patient. The sample comprised 323 patients with cancer attending for out-patient appointments and/or chemotherapy treatment in two major cancer centres in the U.K. 315 patients completed a self-report questionnaire--The Attitudes to Randomised Trials Questionnaire (ARTQ). The results show that the majority of subjects 287 (91.1%) believe that patients should be asked to take part in medical research, but only 242 (76.8%) would be prepared to take part in a study comparing two treatments. If treatment was randomised, only 141 (44.8%) would agree to participate. When given further information about the randomisation procedure, 119 (68.4%) of the 174 (55.2%) who initially said 'no' to randomisation or who were unsure, would change their minds and take part in a trial. The ARTQ discriminated between three categories of patient with the following prevailing attitudes: (a) those who seem comfortable with the concept of randomisation; (b) those with some concerns, who with fuller explanation are prepared to consider randomisation; and (c) those firmly against randomisation and participation in trials whatever information is provided. Prior knowledge of patients' attitudes might assist communication about trials and encourage more doctors to approach eligible patients.

The impact of endocrine therapy on patients with breast cancer: a review of the literature.

This paper reviews studies which have examined the impact of endocrine therapy on the quality of life (QOL) of patients with breast cancer. In patients with primary disease, published studies suggest that endocrine therapies, such as tamoxifen, significantly increase both gynaecological and vasomotor symptoms. However, few studies have been able to demonstrate the impact which these symptoms have on patients' QOL. This failure can be partially attributed to a range of methodological problems. Psychosocial research in advanced disease has largely consisted of randomized controlled studies with QOL as one of several study endpoints. Second generation treatments, such as aromatase inhibitors, have frequently been compared with older treatments, such as progestin therapies. Unfortunately, QOL data reported in these studies have tended to be fairly limited. Problems with existing QOL research in endocrine treatment are discussed and recommendations are made for further work.

The psychological impact of post-operative arm morbidity following axillary surgery for breast cancer: a critical review.

In this paper we review the published research that has investigated the psychological impact of arm morbidity associated with axillary dissection for early breast cancer. This critique is particularly timely given the drive towards minimally invasive techniques, such as sentinel node biopsy, which aim to reduce the incidence and severity of post-operative arm problems. Reported symptoms are multifactorial and include numbness, pain, swelling, weakness/stiffness, and restricted shoulder mobility of the affected arm. Conclusions from the few studies that have investigated the severity, incidence, duration and psychological impact of such disability are often limited by methodological problems. We identify these limitations and examine assessment tools used to determine the psychological impact of lymphoedema. The paper highlights the need for methodological rigor in study design, and the careful selection of appropriate, sensitive, reliable and clinically meaningful outcome measures to evaluate the impact of post-operative arm morbidity.

A qualitative study looking at the psychosocial implications of bilateral prophylactic mastectomy.

The study objective was to explore the attitudes and beliefs of women at high risk of developing breast cancer who accepted or declined bilateral prophylactic mastectomy (BPM). This qualitative study employed semi-structured interviews of 60 women who opted for BPM and 20 women who declined. Interviews took place in the women's own homes. Qualitative analysis led to the generation of a number of categories that provided conceptualisation of the women's primary experiences. These categories included: anxiety; surgery; sexual impact; information; gene testing; reconstruction and support. The study revealed that there is a clear need for information to be written specifically for this patient group and that emotional support for high-risk women offered BPM should be provided.

Psychosocial adjustment after treatment for early breast cancer.

Psychosocial and sexual disturbances are common sequelae to a diagnosis of breast cancer and its treatment. The hope that the development of breast-conserving techniques would protect women from the psychological distress experienced after mastectomy has not been realized. Studies comparing the psychosocial outcome of mastectomy with lumpectomy and radiotherapy reveal an advantage of the breast-conservation groups in terms of body image, but little difference in terms of psychiatric morbidity. Whatever the primary therapy, women still have to confront the fact that they have had cancer, a life-threatening disease which may recur. It is therefore most important that, irrespective of the treatment offered, we improve our understanding of the premorbid personality characteristics and sociodemographic factors that may predispose certain women to failure of adjustment following a diagnosis of breast cancer.

Are members of multidisciplinary teams in breast cancer aware of each other's informational roles?

AIM: To conduct a commissioned survey of multidisciplinary breast team members' expectations of their own and each other's roles in providing different kinds of information to women with breast cancer. DESIGN: Questionnaire based survey. SETTING AND PARTICIPANTS: Health professionals from five multidisciplinary breast care centres within a Sussex health authority. MAIN OUTCOME MEASURES: Interdisciplinary awareness of informational roles played by different team members. RESULTS AND CONCLUSIONS: The results of the team survey suggest that, in most cases, health professionals fulfilled the roles expected of them by the team, with two or three individuals identified as the main providers of information for each topic. However, many more professionals were involved in major discussions without the team's knowledge. The professional consistently playing a major "unseen" role was the breast nurse specialist.

Quality of life measurement in breast cancer.

Appropriate assessment of quality of life parameters should be a mandatory requirement when determining the outcome of different treatments for breast cancer. Such measures provide useful, sometimes counterintuitive information concerning treatment costs and benefits and can help guide the clinician with management decisions. It is important to choose well-validated measures of quality of life to enable comparison between studies assessing the impact of different therapeutic modalities and psychosocial interventions.