Breast density composition
Prevalence of dense breast among Korean women who participated in the KNCSP in 2009 were shown in Table 1. About half of Korean women (53.9%) had dense breast. Prevalence of dense breast were 72.4%, 45.9%, 21.7% and 9.2% for women in forties, fifties, sixties and seventies, respectively. Table 1 showed the number of interval cancers and screen-detected cancer according to women’s age groups and status of breast density, with the ratio from interval cancer to screen-detected cancer (I/S). In total, the I/S ratio was higher among women with dense breasts (0.64) compared to women with non-dense breasts (0.46). However, the higher I/S ratio was not detected among women aged 40-49 years, which might be caused by high recall rates reported among the corresponding age group (Table 1).
Cases of screen-detected and interval cancers in the KNCSP screening rounds
Cases detected in the three rounds of screenings were summarized in Table 2. At first screening round (prevalence screen), 337 and 219 invasive cancers were diagnosed as screen-detected and interval cancers. From in situ cancers, 71 and 26 screen-detected and clinical cancer were diagnosed. At second round (first incident screening round), 193 and 114 invasive breast cancer, and 37 and 16 in situ breast cancers were screen-detected and interval cancers, respectively. 120 and 63 invasive breast cancer, and 24 and 13 in situ breast cancers were screen-detected and interval cancers, respectively, at second incident screen. When examined by age groups, women aged 40-49 years indicated the highest number of breast cancers detectable at screening or within screening-intervals in all screening rounds. Women aged 70 years and older demonstrated the lowest incidence of breast cancer.
Estimated parameters
The rate of transition from healthy to preclinical state, λ1, was 0.0018 (95% CI; 0.0017-0.0019) for total women aged 40-69 years (Table 3). Compared with women in sixties, younger women in forties and fifties demonstrated higher rate transitioning from healthy to preclinical state, estimated to be 0.0019 (95% CI; 0.0017-0.0021) and 0.0020 (95% CI; 0.0017-0.0022), respectively. As the λ1 reflects the incidence level of breast cancer among a population, our results also align with the fact that younger women aged 45-54 years have the highest breast cancer incidence in Korea [20].
In Table 3, the MST, the inverse of λ2, was 2.39 years (95% CI, 2.09 to 2.74) among total women. Higher transition rate from preclinical to clinical state (λ2) among younger women generated shorter MST, 1.98 (95% CI ,1.67 to 2.34), 2.49 (95% CI, 1.93 to 3.23) and 3.07 (95% C, 2.11 to 4.47) years for women aged 40-49, 50-59 and 60-69 years.
The sensitivity of the mammographic screening was estimated to be 0.67 (95% CI, 0.62 to 0.72) for total women, and to be higher among older women, shown as 0.70 (95% CI, 0.62 to 0.77), 0.65 (95% CI, 0.59 to 0.77) and 0.61 (95% CI, 0.54 to 0.61) for women in sixties, fifties and forties, respectively (Table 3).
Hazard of breast density on transition rates
Overall, having 2 to 4 levels of BI-RADS was significantly associated with 1.96 to 2.35-fold accelerated transition from healthy to preclinical state, compared with women with level 1 BI-RADS (Table 3). In addition, women with heterogeneously dense tissue (level 3) and extremely dense tissue (level 4) showed 2.02- and 1.94-times higher hazard on transition to clinical cancer, compared to women with level 1 of BI-RADS. These observations are translated into the significantly shorter MSTs among women with heterogeneously dense breast (1.92 years, 95% CI, 1.64 to 2.27) and extremely dense breast (2.01 years, 95% CI, 1.62 to 2.50). Compared to the current biennial screening protocol from the KNCSP, women with predominantly fatty (Level 1) and scattered fibroglandular tissues (Level 2) have longer-than-2-year MSTs with 3.89 years (95% CI, 2.60 to 5.80) and 2.54 (95% CI, 2.05 to 3.15), respectively.
According to women’s age groups, consistent results were shown that having higher levels of BI-RADS was associated with significantly greater risk of transition from healthy to preclinical state. However, transition from preclinical to clinical cancer was not significantly different by breast density levels among women aged 40-49 and 50-59 years, thus showing overlapped confidence intervals in MSTs across four BI-RADS levels, indicating that breast density as a masking factor did not significantly reduce mammographic screening sensitivity (Table 3). Moreover, the MSTs across all BI-RADS levels among women aged 40 to 59 years included 2-year threshold that the current KNCSP provides mammographic screening.
Women aged 60-69 years with extremely dense breast (Level 4) had significantly higher hazard of transitioning to clinical state, compared to those with predominantly fatty breast (Level 1). The MSTs among women in sixties with non-dense breasts were 4.23 years (95% CI, 2.39 to 7.46) and 2.88 years (95% CI, 2.02 to 4.11), respectively for Level 1 and Level 2, which are longer than the current 2-year KNCSP protocol.
The values of MSTs for women with extremely dense breast tissue were estimated as 2.17 (95% CI, 1.67 to 2.82), 1.71 (95% CI, 1.10 to 2.67) and 1.34 years (95% CI, 0.64 to 2.80) for women in their 40s, 50s and 60s, but the MSTs for older women were modeled by the small number of cancer cases and showed the widest range of confidence intervals (Table 3).