Incidence, Characteristics, and Outcomes of Interval Breast Cancers Compared With Screening-Detected Breast Cancers

Importance: Breast cancer comprises a highly heterogeneous group of diseases. Many breast cancers, particularly the more lethal ones, may not satisfy the assumptions about biology and natural history of breast cancer necessary for screening mammography to be effective. Objectives: To compare tumor characteristics of breast cancers diagnosed within 2 years of a normal screening mammogram (interval breast cancer IBC) with those of screen-detected breast cancers (SBC) and to compare breast cancer-specific mortality of IBC with SBC. Design, Setting, and Participants: In this registry-based cohort study, we collected data about relevant tumor- and patient-related variables on women diagnosed with breast cancer between January 2004 and June 2010 who participated in the population-based screening program in Manitoba, Canada, and those diagnosed with breast cancer outside the screening program in the province. We performed multinomial logistic regression analysis to assess tumor and patient characteristics associated with a diagnosis of IBC compared with SBC. Competing risk analysis was performed to examine risk of death by cancer detection method. Exposures: Breast cancer diagnosis. Main Outcomes and Measures: Differences in tumor characteristics and breast cancer-specific mortality. Results: A total of 69 025 women aged 50 to 64 years had 212 screening mammograms during the study period. There were 1687 breast cancer diagnoses (705 SBC, 206 IBC, 275 were noncompliant, and 501 were detected outside the screening program), and 225 deaths (170 breast cancer-specific deaths). Interval cancers were more likely than SBC to be of high grade and estrogen receptor negative (odds ratio OR, 6.33; 95% CI, 3.73-10.75; P < .001; and OR, 2.88; 95% CI, 2.01-4.13; P < .001, respectively). After a median follow-up of 7 years, breast cancer-specific mortality was significantly higher for IBC compared with SBC cancers (hazard ratio HR 3.55; 95% CI, 2.01-6.28; P < .001), for a sojorn time of 2 years. Non-breast cancer mortality was similar between IBC and SBC (HR, 1.33; 95% CI, 0.43-4.15). Conclusions and Relevance: In this cohort study, interval cancers were highly prevalent in women participating in population screening, represented a worse biology, and had a hazard for breast cancer death more than 3-fold that for SBC. Strategies beyond current mammographic screening practices are needed to reduce incidence, improve detection, and reduce deaths from these potentially lethal breast cancers.