M. Kiderlen

Surgical treatment of early stage breast cancer in elderly: an international comparison

Over 40% of breast cancer patients are diagnosed above the age of 65. Treatment of these elderly patients will probably vary over countries. The aim of this study was to make an international comparison (several European countries and the US) of surgical and radiation treatment for elderly women with early stage breast cancer. Survival comparisons were also made. Data were obtained from national or regional population-based registries in the Netherlands, Switzerland, Ireland, Belgium, Germany, and Portugal. For the US patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Early stage breast cancer patients aged ≥65 diagnosed between 1995 and 2005 were included. An international comparison was made for breast and axillary surgery, radiotherapy after breast conserving surgery (BCS), and relative or cause-specific survival. Overall, 204.885 patients were included. The proportion of patients not receiving any surgery increased with age in many countries; however, differences between countries were large. In most countries more than half of all elderly patients received breast conserving surgery (BCS), with the highest percentage in Switzerland. The proportion of elderly patients that received radiotherapy after BCS decreased with age in all countries. Moreover, in all countries the proportion of patients who do not receive axillary surgery increased with age. No large differences in survival between countries were recorded. International comparisons of surgical treatment for elderly women with early stage breast cancer are scarce. This study showed large international differences in treatment of elderly early stage breast cancer patients, with the most striking result the large proportion of elderly who did not undergo surgery at all. Despite large treatment differences, survival does not seem to be affected in a major way.

External Validity of a Trial Comprised of Elderly Patients With Hormone Receptor–Positive Breast Cancer

BACKGROUND Inclusion in trials is selective, and thus results may not be generalizable to the general population. The aim of this study was to investigate the external validity of randomized clinical trial outcomes for elderly breast cancer patients. METHODS We compared characteristics and outcomes of breast cancer patients (n = 1325) who participated in a randomized clinical trial (Tamoxifen Exemestane Adjuvant Multinational trial) with unselected breast cancer patients of corresponding age from the general population (n = 1056). Dutch patients aged 65 years or older at diagnosis of hormone receptor-positive breast cancer without distant metastases, with either nodal involvement, a tumor greater than 3cm, or a 1 to 3cm histological grade III tumor, who completed local therapy were included. Analyses were stratified by age (65-74 years; ≥75 years). Primary outcome was overall mortality. Multivariable Cox proportional hazards models were used to assess the association between covariables and overall mortality. All statistical tests were two-sided. RESULTS Irrespective of age, patients who participated in the trial had fewer comorbid diseases, a higher socioeconomic status, and smaller tumors (all P < .001). In patients aged 65 to 74 years, those who participated in the trial had a similar overall mortality to patients from the general population (multivariable hazard ratio [HR] = 1.08; 95% confidence interval [CI] = 0.73 to 1.60). Alternatively, in patients aged 75 years or older, those who participated in the trial had a lower overall mortality (multivariable HR = 0.72; 95% CI = 0.55 to 0.95; P = .02) than patients in the general population. CONCLUSIONS Breast cancer trial participants aged 75 years or older do not represent elderly breast cancer patients of corresponding age from the general population, which hampers the external validity of a trial.

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.

Variations in compliance to quality indicators by age for 41,871 breast cancer patients across Europe: A European Society of Breast Cancer Specialists database analysis

OBJECTIVE The aim of this study is to assess age-specific compliance to quality indicators (QIs) regarding the treatment of breast cancer as defined by European Society of Breast Cancer Specialists (EUSOMA) for patients across Europe. METHODS All patients entered into this study were affected by in situ or invasive breast cancer, diagnosed and treated between 2003 and 2012 at 27 Breast Units across Europe, who were entered into the EUSOMA database. Patients were categorised according to age; compliance to thirteen QIs was assessed for each age group and per time period (2003-2007 and 2008-2012). Compliance to QIs was tested by multivariable logistic regression models adjusted for breast unit, incidence year and tumour characteristics. RESULTS Overall, 41,871 patients with a mean age of 59.6years were available for analysis. The highest compliance was reached for patients aged 55-64years and in the time period 2008-2012, whilst the lowest compliance was observed for women aged over 74 or under 40years and in the earlier time period. In multivariable logistic regression models, a significant difference between age categories was shown for 12 out of 13 QIs (P<0.001). Compliance to the QIs for patients aged ⩾75years was significantly lower when compared to patients aged 55-64years for ten QIs, whilst for patients in the youngest age group this was true for seven QIs. CONCLUSION In conclusion, we found that among the 27 included breast units across Europe, compliance to QIs for breast cancer treatment is often lower in the youngest and oldest breast cancer patients, with a tendency to overtreatment in the youngest patients, and to under-treatment in the elderly.

Treatment Strategies and Survival of Older Breast Cancer Patients – An International Comparison between the Netherlands and Ireland

Objectives Forty percent of breast cancers occur among older patients. Unfortunately, there is a lack of evidence for treatment guidelines for older breast cancer patients. The aim of this study is to compare treatment strategy and relative survival for operable breast cancer in the elderly between The Netherlands and Ireland. Material and Methods From the Dutch and Irish national cancer registries, women aged ≥65 years with non-metastatic breast cancer were included (2001-2009). Proportions of patients receiving guideline-adherent locoregional treatment, endocrine therapy, and chemotherapy were calculated and compared between the countries by stage. Secondly, 5-year relative survival was calculated by stage and compared between countries. Results Overall, 41,055 patients from The Netherlands and 5,826 patients from Ireland were included. Overall, more patients received guideline-adherent locoregional treatment in The Netherlands, overall (80% vs. 68%, adjusted p<0.001), stage I (83% vs. 65%, p<0.001), stage II (80% vs. 74%, p<0.001) and stage III (74% vs. 57%, P<0.001) disease. On the other hand, more systemic treatment was provided in Ireland, where endocrine therapy was prescribed to 92% of hormone receptor-positive patients, compared to 59% in The Netherlands. In The Netherlands, only 6% received chemotherapy, as compared 24% in Ireland. But relative survival was poorer in Ireland (5 years relative survival 89% vs. 83%), especially in stage II (87% vs. 85%) and stage III (61% vs. 58%) patients. Conclusion Treatment for older breast cancer patients differed significantly on all treatment modalities between The Netherlands and Ireland. More locoregional treatment was provided in The Netherlands, and more systemic therapy was provided in Ireland. Relative survival for Irish patients was worse than for their Dutch counterparts. This finding should be a strong recommendation to study breast cancer treatment and survival internationally, with the ultimate goal to equalize the survival rates for breast cancer patients across Europe.

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.

The clinical prognostic value of molecular intrinsic tumor subtypes in older breast cancer patients: A FOCUS study analysis

Introduction: It was recently proposed that the molecular breast tumor subtypes are differently distributed in the elderly breast cancer patients, and also lack prognostic value. Given the limited number of elderly patients in previous studies, the aim of this study was to determine the prognostic effect of the molecular intrinsic subtypes in a large older breast cancer population.

Survival and relapse free period of 2926 unselected older breast cancer patients: A FOCUS cohort study

BACKGROUND Previous studies have shown that breast cancer survival decreases with increasing age among older patients who participate in trials. However, trial participants differ from patients in the general population. Therefore, the aim of this study was to evaluate the association between age and breast cancer outcome in an unselected group of older breast cancer patients. METHODS We included all older (65 years and older) consecutive breast cancer patients, diagnosed between 1997 and 2004 from a geographically defined area in the Netherlands. Primary outcome was relative survival and the secondary endpoint was breast cancer recurrence. These outcomes were compared between two age-categories (65-74 years and ≥75 years). RESULTS Five-year relative survival was 91.9% in patients aged 65-74 years, and 84.3% in patients aged ≥75 years. This corresponded with a higher excess risk of death in patients aged ≥75 years as compared to patients aged 65-74 years (multivariable relative excess risk of death: 1.73 (95% CI 1.20-2.49)). The risks of locoregional recurrence, distant recurrence and contralateral breast cancer were similar in both age-categories. CONCLUSIONS Breast cancer survival deteriorates with increasing age among unselected older breast cancer patients. Of note, this was not accompanied by an increased risk of recurrence. This study shows that not only in relatively healthy patients who participate in a trial, but in all older breast cancer patients, outcome deteriorates with increasing age. These findings urge the need for age-specific breast cancer studies, in order to obtain evidence-based medicine in this large and heterogeneous group of patients.

Survival after lumpectomy and mastectomy for early stage invasive breast cancer: The effect of age and hormone receptor status: Correspondence

Hwang and colleagues have observed that women undergoing mastectomy have a poorer disease-specific survival rate compared with women undergoing lumpectomy. One difference is that the women undergoing mastectomy have higher education/higher income (59% are in the upper socioeconomic quintiles for mastectomy compared with 50% for lumpectomy; 22% are in the lower quintiles for mastectomy compared with 29% for lumpectomy). This difference in income may partially explain the difference in the survival rate. Several studies have demonstrated that higher income women consume more alcohol than lower income women, and it has been well established that alcohol consumption increases the risk of breast cancer. In addition, women with higher income are more likely to have received hormone-replacement therapy.

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.