Risk and Mortality of Recurrent Breast Cancer in Stockholm 1985-2005

The purpose of this study was to estimate the risk and mortality of breast cancer recurrences in Swedish women, and to analyse changes over time and variations between patients in different risk groups. Such estimates are of key importance for modelling the cost-effectiveness of different strategies for adjuvant treatment of breast cancer. The study was based on all women diagnosed with breast cancer in Stockholm County between 1985 and 2005. Information about dates for locoregional recurrences, metastatic relapses, new contralateral tumours and death was collected. Cox proportional hazard and Weibull regression models were used to estimate survival functions, where year of diagnosis (dived into 5-year intervals), were included as explanatory variables in the models. The risk of recurrences has decreased during the last 20 years for all three types of recurrence; for metastatic relapse the 5-year risk was reduced from 12.9% to 6.0% from 1985-90 to 2000-2005 . Mortality has also been reduced, resulting in an increased 5-year survival from 52.6% to 64.1% after locoregional recurrence and from 10.4% to 15.5% for metastatic relapse. For contralateral tumours, with a 5-year survival rate of 74.6% in 1985-1990 and 78% 2000-2005, no significant increase was observed. Analysis of risk groups according to TNM classification showed large difference in the risk of metastatic breast cancer between the three defined groups, but small differences for the risk of locoregional recurrences and new contralateral tumours. The findings indicate that the early detection and new treatments have been successful in improving outcome for breast cancer patients and that it is important to use up-to-date information, when assessing the value of new treatment options.Breast cancer; Mortality; Survival; Recurrence; Sweden

Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background:Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods:The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results:A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P < .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions:Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors

Risk of hospitalization and death due to bone fractures after breast cancer: a registry-based cohort study

BACKGROUND: Bone fractures may have an impact on prognosis of breast cancer. The long-term risks of bone fracture in breast cancer patients have not been thoroughly studied. METHODS: Poisson regression was used to investigate the incidence of hospitalisation due to bone fracture comparing women with and without breast cancer based on Swedish National registers. Cox regression was used to investigate the risk of being hospitalised with bone fracture, and subsequent risk of death, in a regional cohort of breast cancer patients. RESULTS: For breast cancer patients, the 5-year risk of bone fracture hospitalisation was 4.8% and the 30-day risk of death following a bone fracture hospitalisation was 2.0%. Compared with the general population, breast cancer patients had incidence rate ratios of 1.25 (95% CI: 1.23-1.28) and 1.18 (95% CI: 1.14-1.22) for hospitalisation due to any bone fracture and hip fracture, respectively. These ratios remained significantly increased for 10 years. Comorbidities (Charlson Comorbidity Index 1) were associated with the risk of being hospitalised with bone fracture. Women taking aromatase inhibitors were at an increased risk as compared with women taking tamoxifen (HR=1.48; 95% CI: 0.98-2.22). Breast cancer patients hospitalised for a bone fracture showed a higher risk of death (HR=1.83; 95% CI: 1.50-2.22) compared with those without bone fracture. CONCLUSIONS: Women with a previous breast cancer diagnosis are at an increased risk of hospitalisation due to a bone fracture, particularly if they have other comorbidities.Swedish Research CouncilSwedish Cancer SocietyFORTEAccepte