Predictors of competing mortality to invasive breast cancer incidence in the Canadian National Breast Screening study.

BACKGROUND: Evaluating the cost-effectiveness of breast cancer screening requires estimates of the absolute risk of breast cancer, which is modified by various risk factors. Breast cancer incidence, and thus mortality, is altered by the occurrence of competing events. More accurate estimates of competing risks should improve the estimation of absolute risk of breast cancer and benefit from breast cancer screening, leading to more effective preventive, diagnostic, and treatment policies. We have previously described the effect of breast cancer risk factors on breast cancer incidence in the presence of competing risks. In this study, we investigate the association of the same risk factors with mortality as a competing event with breast cancer incidence. METHODS: We use data from the Canadian National Breast Screening Study, consisting of two randomized controlled trials, which included data on 39 risk factors for breast cancer. The participants were followed up for the incidence of breast cancer and mortality due to breast cancer and other causes. We stratified all-cause mortality into death from other types of cancer and death from non-cancer causes. We conducted separate analyses for cause-specific mortalities. RESULTS: We found that "age at entry" is a significant factor for all-cause mortality, and cancer-specific and non-cancer mortality. "Menstruation length" and "number of live births" are significant factors for all-cause mortality, and cancer-specific mortality. "Ever noted lumps in right/left breasts" is a factor associated with all-cause mortality, and non-cancer mortality. CONCLUSIONS: For proper estimation of absolute risk of the main event of interest common risk factors associated with competing events should be identified and considered.

Incidence of invasive breast cancer in the presence of competing mortality: the Canadian National Breast Screening Study.

Mortality due to causes other than breast cancer is a potential competing risk which may alter the incidence probability of breast cancer and as such should be taken into account in predictive modelling. We used data from the Canadian National Breast Screening Study (CNBSS), which consist of two randomized controlled trials designed to evaluate the efficacy of mammography among women aged 40-59. The participants in the CNBSS were followed up for incidence of breast cancer and mortality due to breast cancer and other causes; this allowed us to construct a breast cancer risk prediction model while taking into account mortality for the same study population. In this study, we use 1980-1989 as the study period. We exclude the prevalent cancers from the CNBSS to estimate the probability of developing breast cancer, given the fact that women were cancer-free at the beginning of the follow-up. By the end of 1989, from 89,434 women, 944 (1.1 %) were diagnosed with invasive breast cancer, 922 (1.0 %) died from causes other than breast cancer, and 87,568 (97.9 %) were alive and not diagnosed with invasive breast cancer. We constructed a risk prediction model for invasive breast cancer based on 39 risk factors collected at the time of enrolment or the initial physical examination of the breasts. Age at entry (HR 1.07, 95 % CI 1.05-1.10), lumps ever found in left or right breast (HR 1.92, 95 % CI 1.19-3.10), abnormality in the left breast (HR 1.26, 95 % CI 1.07-1.48), history of other breast disease, family history of breast cancer score (HR 1.01, 95 % CI 1.00-1.01), years menstruating (HR 1.02, 95 % CI 1.01-1.03) and nulliparity (HR 1.70, 95 % CI 1.23-2.36) are the model's predictors. We investigated the effects of time-dependent factors. The model is well calibrated with a moderate discriminatory power (c-index 0.61, 95 % CI 0.59-0.63); we use it to predict the 9-year risk of developing breast cancer for women of different age groups. As an example, we estimated the probability of invasive cancer at 5 years after enrolment to be 0.00448, 0.00556, 0.00691, 0.00863, and 0.01034, respectively, for women aged 40, 45, 50, 55, and 59, all of whom had never noted lumps in their breasts, had 32 years of menstruating, 1-2 live births, no other types of breast disease and no abnormality found in their left breasts. The results of this study can be used by clinicians to identify women at high risk of breast cancer for screening intervention and to recommend a personalized intervention plan. The model can be also utilized by a woman as a breast cancer risk prediction tool.

Optimizing Canadian breast cancer screening strategies: a perspective for action.

While controversies regarding optimal breast cancer screening modalities, screening start and end ages, and screening frequencies continue to exist, additional population-based randomized trials are unlikely to be initiated to examine these concerns. Simulation models have been used to evaluate the efficacy and effectiveness of various breast cancer screening strategies, however these models were all developed using US data. Currently, there is a need to examine the optimal screening and treatment policies in the Canadian context. In this commentary, we discuss the current controversies pertaining to breast cancer screening, and describe the fundamental components of a simulation model, which can be used to inform breast cancer screening and treatment policies.