N.A. de Glas

Diabetes in relation to breast cancer relapse and all-cause mortality in elderly breast cancer patients: a FOCUS study analysis

BACKGROUND In developed countries, 40% of breast cancer patients are >65 years of age at diagnosis, of whom 16% additionally suffer from diabetes. The aim of this study was to assess the impact of diabetes on relapse-free period (RFP) and overall mortality in elderly breast cancer patients. PATIENTS AND METHODS Patients were selected from the retrospective FOCUS cohort, which contains detailed information of elderly breast cancer patients. RFP was calculated using Fine and Gray competing risk regression models for patients with diabetes versus patients without diabetes. Overall survival was calculated by Cox regression models, in which patients were divided into four groups: no comorbidity, diabetes only, diabetes and other comorbidity or other comorbidity without diabetes. RESULTS Overall, 3124 patients with non-metastasized breast cancer were included. RFP was better for patients with diabetes compared with patients without diabetes (multivariable HR 0.77, 95% CI 0.59-1.01), irrespective of other comorbidity and most evident in patients aged ≥75 years (HR 0.67, 95% CI 0.45-0.98). The overall survival was similar for patients with diabetes only compared with patients without comorbidity (HR 0.86, 95% CI 0.45-0.98), while patients with diabetes and additional comorbidity had the worst overall survival (HR 1.70, 95% CI 1.44-2.01). CONCLUSION When taking competing mortality into account, RFP was better in elderly breast cancer patients with diabetes compared with patients without diabetes. Moreover, patients with diabetes without other comorbidity had a similar overall survival as patients without any comorbidity. Possibly, unfavourable effects of (complications of) diabetes on overall survival are counterbalanced by beneficial effects of metformin on the occurrence of breast cancer recurrences.

Age and the effect of physical activity on breast cancer survival: A systematic review

The effect of physical activity (PA) on cancer survival is still the topic of debate in oncology research focusing on survivorship, and has been investigated retrospectively in several large clinical trials. PA has been shown to improve quality of life, fitness and strength, and to reduce depression and fatigue. At present, there is a growing body of evidence on the effects of PA interventions for cancer survivors on health outcomes. PA and functional limitations are interrelated in the elderly. However the relationship between breast cancer survival and PA in older breast cancer patients has not yet been fully investigated. Our systematic review of the existing literature on this topic yielded seventeen studies. Most reports demonstrated an improved overall and breast cancer-specific survival. Furthermore, in studies that compared younger women with older or postmenopausal women, it was suggested that the beneficial effect of PA may be even greater in older women. Understanding the interaction between physical functioning and cancer survival in older breast cancer patients is key, and may contribute to successful treatment and survival. In this population of cancer survivors it is therefore imperative to embark on research focused on improving physical functioning in the context of comorbidities and functional limitations.

Validity of the online PREDICT tool in older patients with breast cancer: a population-based study

Background:Predicting breast cancer outcome in older patients is challenging, as it has been shown that the available tools are not accurate in older patients. The PREDICT tool may serve as an alternative tool, as it was developed in a cohort that included almost 1800 women aged 65 years or over. The aim of this study was to assess the validity of the online PREDICT tool in a population-based cohort of unselected older patients with breast cancer.Methods:Patients were included from the population-based FOCUS-cohort. Observed 5- and 10-year overall survival were estimated using the Kaplan–Meier method, and compared with predicted outcomes. Calibration was tested by composing calibration plots and Poisson Regression. Discriminatory accuracy was assessed by composing receiver-operator-curves and corresponding c-indices.Results:In all 2012 included patients, observed and predicted overall survival differed by 1.7%, 95% confidence interval (CI)=−0.3–3.7, for 5-year overall survival, and 4.5%, 95% CI=2.3–6.6, for 10-year overall survival. Poisson regression showed that 5-year overall survival did not significantly differ from the ideal line (standardised mortality ratio (SMR)=1.07, 95% CI=0.98–1.16, P=0.133), but 10-year overall survival was significantly different from the perfect calibration (SMR=1.12, 95% CI=1.05–1.20, P=0.0004). The c-index for 5-year overall survival was 0.73, 95% CI=0.70–0.75, and 0.74, 95% CI=0.72–0.76, for 10-year overall survival.Conclusions:PREDICT can accurately predict 5-year overall survival in older patients with breast cancer. Ten-year predicted overall survival was, however, slightly overestimated.

Assessing treatment effects in older breast cancer patients: Systematic review of observational research methods

Solid evidence of treatment effects in older women with breast cancer is lacking, as they are generally underrepresented in randomized clinical trials on which guideline recommendations are based. An alternative way to study treatment effects in older patients could be to use data from observational studies. However, using appropriate methods in analyzing observational data is a key condition in order to draw valid conclusions, as directly comparing treatments generally results in biased estimates due to confounding by indication. The aim of this systematic review was to investigate the methods that have been used in observational studies that assessed the effects of breast cancer treatment on survival, breast cancer survival and recurrence in older patients (aged 65 years and older). Studies were identified through systematic review of the literature published between January 1st 2009 and December 13th 2013 in the PubMed database and EMBASe. Finally, 31 studies fulfilled the inclusion criteria. Of these, 22 studies directly compared two treatments. Fifteen out of these 22 studies addressed the problem of confounding by indication, while seven studies did not. Nine studies used some form of instrumental variable analysis. In conclusion, the vast majority of observational studies that investigate treatment effects in older breast cancer patients compared treatments directly. These studies are therefore likely to be biased. Observational research will be essential to improve treatment and outcome of older breast cancer patients, but the use of accurate methods is essential to draw valid conclusions from this type of data.

Survival of older patients with metastasised breast cancer lags behind despite evolving treatment strategies--a population-based study.

BACKGROUND Older women are more likely to be diagnosed with primary metastasised breast cancer than their younger counterparts. Evolving treatment strategies of metastasised breast cancer have resulted in improved survival in younger patients, but it remains unclear if this improvement has occurred in older patients as well. The aim of this study was to assess changes in treatment strategies over time in relation to overall and relative survival of older patients compared to younger patients with primary metastasised breast cancer. METHODS All patients with a breast cancer diagnosis and distant metastases at first presentation (stage IV), between 1990 and 2012, were selected from the Netherlands Cancer Registry. Changes in treatment over time per age-group (<65 years, 65-75 years and >75 years) were assessed using logistic regression. Overall survival over time was calculated using Cox Regression Models and relative survival was assessed using the Ederer II method. RESULTS Overall, 14,310 patients were included. Treatment strategies have strongly changed in the past twenty years; especially the use of chemotherapy has increased (P<0.001 in all age-groups). Overall survival of patients <65 has significantly improved (Hazard Ratio (HR) per year 0.98, 95% Confidence Interval (CI) 0.98-0.99, P<0.001), but the survival of older patients has not improved (HR 1.00, 95% CI 0.99-1.01, P=0.86 for patients aged 65-75 and HR 1.00, 95% CI 1.00-1.01, P=0.46 for patients aged >75). Similarly, relative survival has improved in patients <65 but not in women aged 65-75 and >75. CONCLUSION Overall and relative survival of older patients with metastasised breast cancer at first presentation have not improved in recent years in contrast with the survival of younger patients, despite increased treatment with chemotherapy for women of all ages. Future studies should focus on stratification models that can be used to predict which patients may benefit from specific treatment options.

Targeted therapy in older women with breast cancer – What's the target?

In this review, the results of the FOCUS (Female breast cancer in the elderly: Optimizing Clinical guidelines USing clinico-pathological and molecular data) program are summarized. This study was originally designed with the aim to define guidelines for the treatment of older women with breast cancer. With data from several studies within FOCUS, a prediction model can be constructed. Such a model helps to define individualized treatment for older patients with breast cancer, taking into account tumour characteristics and patient-related factors. At a clinical level, this model can provide the physician and the patient with accurate prediction to assist on the decision making of treatment strategies: this results into individualized treatment, not based on one individual marker, but on different pillars related to the patient, the tumour and the most suitable, appropriate treatment.

Multidisciplinary development of the Geriatric Core Dataset for clinical research in older patients with cancer: A French initiative with international survey

BACKGROUND To define a core set of geriatric data to be methodically collected in clinical cancer trials of older adults, enabling comparison across trials. PATIENTS AND METHODS Following a consensus approach, a panel of 14 geriatricians from oncology clinics identified seven domains of importance in geriatric assessment. Based on the international recommendations, geriatricians selected the mostly commonly used tools/items for geriatric assessment by domain (January-October 2015). The Geriatric Core Dataset (G-CODE) was progressively developed according to RAND appropriateness ratings and feedback during three successive Delphi rounds (July-September 2016). The face validity of the G-CODE was assessed with two large panels of health professionals (55 national and 42 international experts) involved both in clinical practice and cancer trials (March-September 2017). RESULTS AND DISCUSSION After the last Delphi round, the tools/items proposed for the G-CODE were the following: (1) social assessment: living alone or support requested to stay at home; (2) functional autonomy: Activities of Daily Living (ADL) questionnaire and short instrumental ADL questionnaire; (3) mobility: Timed Up and Go test; (4) nutrition: weight loss during the past 6 months and body mass index; (5) cognition: Mini-Cog test; (6) mood: mini-Geriatric Depression Scale and (7) comorbidity: updated Charlson Comorbidity Index. More than 70% of national experts (42 from 20 cities) and international experts (31 from 13 countries) participated. National and international surveys showed good acceptability of the G-CODE. Specific points discussed included age-year cut-off, threshold of each tool/item and information about social support, but no additional item was proposed. CONCLUSION We achieved formal consensus on a set of geriatric data to be collected in cancer trials of older patients. The dissemination and prospective use of the G-CODE is needed to assess its utility.