Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

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Breast density predicts endocrine treatment outcome in the adjuvant setting

PMCID: PMC3680935See related research article by Kim et al., http://breast-cancer-research.com/content/14/4/R10

Risk Models for Breast Cancer and Their Validation.

Strategies to prevent cancer and diagnose it early when it is most treatable are needed to reduce the public health burden from rising disease incidence. Risk assessment is playing an increasingly important role in targeting individuals in need of such interventions. For breast cancer many individual risk factors have been well understood for a long time, but the development of a fully comprehensive risk model has not been straightforward, in part because there have been limited data where joint effects of an extensive set of risk factors may be estimated with precision. In this article we first review the approach taken to develop the IBIS (Tyrer-Cuzick) model, and describe recent updates. We then review and develop methods to assess calibration of models such as this one, where the risk of disease allowing for competing mortality over a long follow-up time or lifetime is estimated. The breast cancer risk model model and calibration assessment methods are demonstrated using a cohort of 132,139 women attending mammography screening in the State of Washington, USA

Use of the concordance index for predictors of censored survival data.

The concordance index is often used to measure how well a biomarker predicts the time to an event. Estimators of the concordance index for predictors of right-censored data are reviewed, including those based on censored pairs, inverse probability weighting and a proportional-hazards model. Predictive and prognostic biomarkers often lose strength with time, and in this case the aforementioned statistics depend on the length of follow up. A semi-parametric estimator of the concordance index is developed that accommodates converging hazards through a single parameter in a Pareto model. Concordance index estimators are assessed through simulations, which demonstrate substantial bias of classical censored-pairs and proportional-hazards model estimators. Prognostic biomarkers in a cohort of women diagnosed with breast cancer are evaluated using new and classical estimators of the concordance index.This work was funded by Cancer Research UK (grant number C569/A16891)

Early participant-reported symptoms as predictors of adherence to anastrozole in the International Breast Cancer Intervention Studies II

Background: Anastrozole reduces breast cancer risk in women at high risk, but implementing preventive therapy in clinical practice is difficult. Here, we evaluate adherence to anastrozole in the International Breast Cancer Intervention Study (IBIS) II prevention and Ductal Carcinoma in Situ (DCIS) trials, and its association with early symptoms. Patients and methods: In the prevention trial, 3864 postmenopausal women were randomized to placebo vs. anastrozole. 2980 postmenopausal women with DCIS were randomized to tamoxifen vs. anastrozole. Adherence to trial medication was calculated using the Kaplan-Meier method and all Pvalues were two-sided. Results: In the prevention trial, adherence was 65.8% (anastrozole (65.7%) vs. placebo (65.9%); HR=0.97 (0.87-1.09), p=0.6). Adherence was lower for those reporting arthralgia in the placebo group (p=0.02) or gynecological symptoms in the anastrozole group (P=0.003), compared with those not reporting these symptoms at 6 months. In the DCIS study, adherence was 66.7% (anastrozole (67.5%) vs. tamoxifen (65.8%); HR=1.06 (0.94-1.20), p=0.4). Hot flashes were associated with greater adherence in the anastrozole arm (p=0.02). In both studies, symptoms were mostly mild or moderately severe, and adherence decreased with increasing severity for most symptoms. Dropouts were highest in the first 1.5 years of therapy in both trials. Conclusions: In the IBIS-II prevention and DCIS trials, over two-thirds of women were adherent to therapy, with no differences by treatment groups. Participants who reported specific symptoms in the IBIS-II prevention trial had a small but significant effect on adherence, which strengthened as severity increased. Strategies to promote adherence should target the first year of preventive therapy