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

Question What are the differences and similarities in characteristics and outcomes of breast cancers detected by mammographic screening vs those detected between screening mammograms (interval cancers) in women participating in a population-based screening program? Findings In this cohort study of 69025 women, interval breast cancers accounted for one-fourth of breast cancers in routinely screened women, were 6 times more likely to be grade III, and had 3.5 times increased hazards of breast cancer death compared with screen-detected cancers. Meaning Heterogeneity in breast cancer defies assumptions necessary for screening mammography in its current form to be maximally effective; strategies beyond routine screening mammography are needed to prevent, detect, and avert deaths from the more lethal interval breast cancers. This population-based cohort study examines breast cancer-specific mortality rates associated with interval breast cancer compared with those of screen-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 69025 women aged 50 to 64 years had 212579 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.