W. van de Water

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.

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

BACKGROUNDnIn 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.nnnPATIENTS AND METHODSnPatients 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.nnnRESULTSnOverall, 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).nnnCONCLUSIONnWhen 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.

Postoperative complications and survival of elderly breast cancer patients: a FOCUS study analysis

Old age is associated with comorbidity and decreased functioning which influences treatment decisions in elderly breast cancer patients. The purpose of this study was to identify risk factors for complications after breast cancer surgery in elderly patients, and to assess mortality in patients with postoperative complications. The FOCUS cohort is a detailed retrospective cohort of all breast cancer patients aged 65xa0years and older who were diagnosed between 1997 and 2004 in the South-West of the Netherlands. Risk factors for postoperative complications were assessed using univariable and multivariable logistic regression models. One-year survival and overall survival were calculated using univariable and multivariable Cox Regression models, and relative survival was calculated according to the Ederer II method. 3179 patients received surgery, of whom 19xa0% (nxa0=xa0618) developed 1 or more postoperative complication(s). The odds ratio of having postoperative complications increased with age [OR 1.85 (95xa0% confidence interval (CI) 1.37–2.50, pxa0=xa00.001) in patients >85xa0years] and number of concomitant diseases [OR 1.71 (95xa0% CI 1.30–2.24, pxa0≤xa00.001) for 4 or more concomitant diseases]. One-year overall survival, overall survival, and relative survival were worse in patients with postoperative complications [multivariable HR 1.49 (95xa0% CI 1.05–2.11), pxa0=xa00.025. HR 1.21, (95xa0% CI 1.07–1.36), pxa0=xa00.002 and RER 1.19 (95xa0% CI 1.05–1.34), pxa0=xa00.006 respectively]. Stratified for comorbidity, relative survival was lower in patients without comorbidity only. Increasing number of concomitant disease increased the risk of postoperative complications. Although elderly patients with comorbidity did have a higher risk of postoperative complications, relative mortality was not higher in this group. This suggests that postoperative complications in itself did not lead to higher relative mortality, but that the high relative mortality was most likely due to geriatric parameters such as comorbidity or poor physical function.

Contralateral breast cancer risk in relation to tumor morphology and age—in which patients is preoperative MRI justified?

AbstractnIdentification of patients who are at increased risk for contralateral breast cancer is essential to determine which patients should be routinely screened for contralateral breast cancer using MRI. The aim of this study was to assess the association of age and tumor morphology with contralateral breast cancer incidence in a large, nationwide population-based study in the Netherlands. All patients with breast cancer stage I–III, diagnosed between 1989 and 2009, were selected from the Netherlands Cancer Registry. The association between contralateral breast cancer risk with tumor morphology and age was assessed using competing-risk regression according to Fine & Gray. Overall, 194,898 patients were included. In multivariable analyses, lobular tumors were significantly associated with an increased risk of contralateral breast cancer within 6xa0months (cumulative incidence 1.9xa0%, subdistribution hazard ratio (SHR) 1.17, 95xa0% confidence interval (CI) 1.06–1.30 compared with 1.3xa0% in ductal tumors, pxa0=xa00.002). Age was also associated with an increased risk of contralateral breast cancer within 6xa0months (SHR 2.34, 95xa0% CI 2.08–2.62, pxa0<xa00.002 for patients over the age of 75 as compared to patients younger than 50xa0years). The absolute risk of contralateral breast cancer within 6xa0months is only slightly increased in patients with a lobular tumor and older patients. In our view, this small increased risk does not justify standard use of preoperative MRI based on tumor morphology or age alone. We propose a more personalized strategy in which additional risk factors (family history, prognosis of primary tumor, and others) may play a role.

Impact of age on breast cancer mortality and competing causes of death at 10 years follow-up in the adjuvant TEAM trial

AIMnDue to increasing life expectancy, patients with breast cancer remain at risk of dying due to breast cancer over a long time. This study aims to assess the impact of age on breast cancer mortality and other cause mortality 10 years after diagnosis.nnnMETHODSnPostmenopausal patients with hormone-receptor positive breast cancer were included in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial between 2001 and 2006. Age at diagnosis was categorised as <65 years (nxa0=xa03369), 65-74 years (nxa0=xa01896) and ≥75 years (nxa0=xa0854). Breast cancer mortality was assessed considering other cause mortality as competing event using competing risk analysis.nnnRESULTSnAfter a median follow-up of 9.8 years (interquartile range 8.0-10.3), cumulative incidence of breast cancer mortality increased with increasing age (age <65 years, 11.7% [95% confidence interval {CI}: 10.2-13.2]; 65-74 years, 12.7% (11.2-14.2) and ≥75 years, 15.6% (13.1-18.0)). Univariate subdistribution hazard ratio (sHR) increased with increasing age (age: 65-74 years, sHR: 1.08, 95% CI: 0.92-1.27 and ≥75 years sHR: 1.30, 95% CI: 1.06-1.58, Pxa0=xa00.013). Multivariable sHR adjusted for tumour and treatment characteristics increased with age but did not reach significance (age 65-74 years, sHR: 1.11, 95% CI: 0.94-1.31; ≥75 years, sHR: 1.18, 95% CI: 0.94-1.48, Pxa0=xa00.055).nnnCONCLUSIONnTen years after diagnosis, older age at diagnosis is associated with increasing breast cancer mortality in univariate analysis, but it did not reach significance in multivariable analysis. This is not outweighed by a substantially higher other cause mortality with older age. This underlines the need to improve the balance between undertreatment and overtreatment in older patients with breast cancer. The trial was registered in International Trial Databases (ClinicalTrials.govNCT00279448, NCT00032136, and NCT00036270; the Netherlands Trial Registry NTR267).

Letter to the editor - author's response.

The authors would like to thank Dr. Montemurro for his important comments. It is indeed important to shed light on our primary hypothesis and not ignore these results. Numerous reports have addressed the differences between lobular and ductal breast cancer, especially with respect to chemosensitivity and tumour biology, thereby implying that different treatment approaches may, in time, become necessary. A retrospective analysis of the BIG 1-98 trial showed a differential efficacy of endocrine therapy for ductal and lobular breast cancer. In the latter study, patients were randomised to 5 years of tamoxifen versus 5 years of letrozole treatment. The question arose whether the lack of a treatment by histological subtype interaction in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) study may have been diluted by the switchdesign; in lobular cancer, the switch to exemestane after 2.5 years of tamoxifen may have triggered a recovery from the original risk reduction in favour of exemestane. To explore this valuable hypothesis, we tested for the proportionality of the hazard ratios. Fig. 1 shows the cumulative incidence of overall recurrence by treatment, stratified by histological subtype. Both in ductal and lobular cancer, the proportional hazard assumption holds (Schoenfeld residuals test p = 0.33; p = 0.43, respectively). In addition, we investigated treatment effect in the first 2.5 years of follow up, as indicated with the dotted line in the figure, i.e. the time period before the switch. Survival analysis revealed similar results to the primary