The impact of Oncotype DX testing on adjuvant chemotherapy decision making in 1-3 node positive breast cancer.

BACKGROUND: Oncotype DX testing has reduced the use of adjuvant chemotherapy in node-negative early breast cancer but less is known about its impact in node positive patients. AIM: This study aimed to investigate the impact of Oncotype DX gene assay testing on the decision to offer adjuvant chemotherapy in oestrogen positive, human epidermal growth factor receptor 2 negative, 1-3 lymph node positive patients. METHODS: Retrospective review of all node positive patients who underwent Oncotype DX testing at a single centre. Clinicopathological data, as well as estimated survival benefit data (from the PREDICT tool), was evaluated by a multidisciplinary group of surgeons and oncologists. Treatment decisions based on clinicopathological data were compared to recurrence scores (RS). A cut off RS > 30 was used to offer adjuvant chemotherapy. RESULTS: The 69 patients were identified, of which 9 (13%) had an RS > 30 and assigned a high-genomic risk of recurrence. The 32 patients (46.4%) were offered adjuvant chemotherapy. Overall based on the use of the RS, the decision to offer adjuvant chemotherapy changed in 36% of patients, and ultimately 24 patients (34.7%) would have been spared chemotherapy. CONCLUSION: Using clinicopathological data alone to make decisions regarding adjuvant chemotherapy in node positive breast cancer leads to overtreatment. Additional information on tumour biology as assessed by the Oncotype DX RS helps to select those patients who will benefit from adjuvant chemotherapy and spare patients from unnecessary chemotherapy.

The impact of a supranetwork multidisciplinary team (SMDT) on decision-making in testicular cancers: a 10-year overview of the Anglian Germ Cell Cancer Collaborative Group (AGCCCG).

BACKGROUND: The germ cell supranetwork multidisciplinary team (SMDT) for the Anglian Network covers a population of 7.5 million. METHODS: We reviewed 10 years of SMDT discussion and categorised them into five domains ((1) overall outcome, (2) chemotherapy regimens-untreated disease and salvage therapy, (3) radiology, (4) pathology and (5) complex cases) to assess the impact of the SMDT. RESULTS: A total of 2892 new cases were reviewed. In the first 5 years, patients with good prognosis disease had poorer survival in low-volume vs high-volume centres (87.8 vs 95.3, p = 0.02), but the difference was no longer significant in the last 5 years (93.3 vs 95.1, p = 0.30). Radiology review of 3206 scans led to rejection of the diagnosis of progression in 26 cases and a further 10 cases were down-staged. There were 790 pathology reviews by two specialised uropathologists, which lead to changes in 75 cases. 18F-fluorodeoxyglucose (18FDG) PET-CT was undertaken during this time period but did not help to predict who would have viable cancer. A total of 26 patients with significant mental health issues who were unable to give informed consent were discussed. CONCLUSION: SMDT working has led to an improvement in outcomes and refining of treatment in patients with germ cell tumours.

Can the Cancer-related Fatigue Case-definition Criteria Be Applied to Chronic Medical Illness? A Comparison between Breast Cancer and Systemic Sclerosis.

OBJECTIVE: Fatigue is a crucial determinant of quality of life across rheumatic diseases, but the lack of agreed-upon standards for identifying clinically significant fatigue hinders research and clinical management. Case definition criteria for cancer-related fatigue were proposed for inclusion in the International Classification of Diseases. The objective was to evaluate whether the cancer-related fatigue case definition performed equivalently in women with breast cancer and systemic sclerosis (SSc) and could be used to identify patients with chronic illness-related fatigue. METHODS: The cancer-related fatigue interview (case definition criteria met if ≥ 5 of 9 fatigue-related symptoms present with functional impairment) was completed by 291 women with SSc and 278 women successfully treated for breast cancer. Differential item functioning was assessed with the multiple indicator multiple cause model. RESULTS: Items 3 (concentration) and 10 (short-term memory) were endorsed significantly less often by women with SSc compared with cancer, controlling for responses on other items. Omitting these 2 items from the case definition and requiring 4 out of the 7 remaining symptoms resulted in a similar overall prevalence of cancer-related fatigue in the cancer sample compared with the original criteria (37.4% vs 37.8%, respectively), with 97.5% of patients diagnosed identically with both definitions. Prevalence of chronic illness-related fatigue was 36.1% in SSc using 4 of 7 symptoms. CONCLUSION: The cancer-related fatigue criteria can be used equivalently to identify patients with chronic illness-related fatigue when 2 cognitive fatigue symptoms are omitted. Harmonized definitions and measurement of clinically significant fatigue will advance research and clinical management of fatigue in rheumatic diseases and other conditions.

Identification of factors associated with cancer related fatigue syndrome in disease-free breast cancer patients after completing primary treatment.

This study is an analysis of variables associated with women who meet the criteria for after completion of successful primary treatment for breast cancer. This analysis was conducted to identify factors independently associated with cancer related fatigue syndrome using a combined dataset from two non-overlapping studies conducted on similar populations. Participants who were clinically (and radiologically) disease-free, between 3 months and 2 years after treatment, were recruited from a single centre. A diagnostic interview was conducted to ascertain whether they met the criteria for cancer related fatigue syndrome. We analysed a number of treatment, laboratory and questionnaire variables between groups. Those that were significantly different were entered into a logistic model. A total of 278 subjects (105 cases of cancer related fatigue syndrome and 173 controls who did not meet the criteria) were analysed. A number of questionnaire responses were significantly different including all of the European Organisation for the Research and Treatment of Cancer core 30 item quality of life questionnaire (EORTC QLQ c30) and Breast questionnaire 23 item subgroup scores. 11 variables were entered into the final model and 5 were independently associated with cancer related fatigue syndrome: Hospital anxiety and depression scale score, EORTC pain and insomnia scales, breast systemic side effects and plasma sodium. There was, however, no association with demographic or treatment variables. As a conclusion, cancer related fatigue syndrome after treatment is linked with sub-clinical mood pain and subjective sleep disturbance and with the side effects of systemic treatment. This study is unable to determine whether these associations are causal, but they provide a potential target for interventions to manage the symptoms of cancer related fatigue syndrome.

Evaluation of central serotonin sensitivity in breast cancer survivors with cancer-related fatigue syndrome.

CONTEXT: Increased central serotonin sensitivity is hypothesized to contribute toward the development of cancer-related fatigue syndrome (CRFS). OBJECTIVES: To compare the responses of breast cancer survivors with or without CRFS to the buspirone challenge test (an index of central serotonin sensitivity). METHODS: Disease-free women who had successfully completed treatment for early-stage breast cancer were assessed. On the basis of the diagnostic interview for CRFS and a structured psychiatric interview, women were classified as either "cases" of CRFS or "controls." Women with comorbid psychiatric diagnoses were excluded. Volunteers underwent a challenge test using buspirone (a serotonin-selective agonist) using a double-blind, randomized, placebo-controlled protocol. Cortisol and prolactin responses were assessed at hourly intervals for the four hours after administration of buspirone. RESULTS: Fourteen cases of CRFS and 28 controls participated in the study. There were no significant differences in baseline or stimulated cortisol release after buspirone challenge. There were differences neither in basal prolactin levels in the two groups nor in the total prolactin response to buspirone (as measured using the area under the curve). In patients with CRFS, peak prolactin response occurred at 120 minutes and sustained until 180 minutes post buspirone. In controls, peak prolactin response occurred at 60 minutes and then began to decline. CONCLUSIONS: This study has demonstrated the utility and acceptability of buspirone as a probe of central serotonin sensitivity in this population. No evidence was found for alterations in central serotonin sensitivity in patients with CRFS. Conclusions are tentative, however, because poor recruitment resulted in a small sample and an underpowered comparison.

Evaluation of screening instruments for depression and anxiety in breast cancer survivors.

Although cases of anxiety and depression post-breast cancer can be reliably identified using a structured psychiatric interview, such interviews are time consuming for both practitioner and patient and effective screening tools would increase detection rates. The purpose of this study was to evaluate the effectiveness of the Edinburgh Depression Scale (EDS) and the Hospital Anxiety and Depression Scale (HADS) in screening for depression and anxiety in a population of breast cancer survivors. For this purpose, The Structured Clinical Interview for the Diagnostic and Statistical Manual of mental disorders was administered to 200 breast cancer survivors to identify those suffering from an anxiety and/or depressive disorder. All study participants also completed the EDS and the HADS. Using the recommended cut-off score of >12 to screen for depression, the sensitivity and specificity of the EDS were found to be 72 and 90%, respectively. Lowering the cut-off score to >9 resulted in a sensitivity of 94% and a specificity of 78%. At the recommended cut-off score of >10, the HADS had a sensitivity of 50% and a specificity of 97% for depression, and a sensitivity of 71% and a specificity of 86% when screening for anxiety. A HADS total score (HADS-T) of >13 and an EDS of >9 had sensitivities of 96 and 91% and specificities of 74 and 84%, respectively, in screening for anxiety and/or depression. In conclusion, the study demonstrated that both the EDS and HADS can be used reliably as screening tests for anxiety and depression in this cohort. In both cases, a lower cut-off score than normally recommended delivers optimal screening properties.

Evaluation of screening instruments for cancer-related fatigue syndrome in breast cancer survivors.

PURPOSE: Cases of cancer-related fatigue syndrome (CRFS) can be reliably indentified using a diagnostic interview combined with a structured psychiatric interview. However, these interviews are time consuming to conduct, require specialist training, and are not suitable for routine clinical use. The purpose of this study was to identify whether a screening questionnaire could identify patients at high risk of clinically significant fatigue who should be considered for a suitable intervention. PATIENTS AND METHODS: The diagnostic interview for CRFS and the structured clinical interview for the diagnostic and statistical manual of mental disorders were used in order to identify breast cancer survivors who fulfilled the criteria for CRFS. Two fatigue questionnaires (the Bidimensional Fatigue Scale [BFS] and the Functional Assessment of Cancer Therapy-Fatigue subscale [FACT-F]) were administered in order to determine their screening properties. RESULTS: Two hundred women were interviewed and 60 women fulfilled the criteria for CRFS. The BFS cutoff score of 11 had a sensitivity of 92%, a specificity of 53%, a positive predictive value (PPV) of 46%, and a negative predictive value (NPV) of 94%. The FACT-F cutoff score of 36 had a sensitivity of 80%, a specificity of 71%, a PPV of 55%, and a NPV of 89%. CONCLUSION: The BFS and FACT-F cutoff scores can be used to identify breast cancer survivors at higher risk of clinically significant ongoing post treatment fatigue. Neither scale can be used as a diagnostic instrument for CRFS.

Investigation of diagnostic criteria for cancer-related fatigue syndrome in patients with advanced cancer: a feasibility study.

The primary aim of this study was to explore the feasibility of applying diagnostic criteria for cancer-related fatigue syndrome (CRFS) in patients with advanced cancer. A secondary aim was to assess the use of screening instruments for fatigue and depression in this population. Patients with advanced cancer (n=16) were interviewed using the Diagnostic Interview for CRFS and a semi-structured psychiatric interview. Subjects also completed the Bi-dimensional Fatigue Scale (BFS) and the Edinburgh Postnatal Depression Scale (EPDS) as screening instruments. The prevalence of psychiatric disorders was 50% (8/16). The EPDS was found to have a sensitivity of 67% and a specificity of 100% for detecting depression. The prevalence of clinically significant fatigue symptoms was 62.5% (10/16). The BFS was found to have a sensitivity of 70% and a specificity of 64% for detecting clinically significant fatigue. The prevalence of CRFS was 12.5% (2/16).