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

Abstract

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.