IMPACT OF TUMOR GROWTH RATE AND BREAST DENSITY ON MAMMOGRAPHIC SCREENING OUTCOMES IN WOMEN AGES 40 TO 49 YEARS

PURPOSE

To evaluate the impact of the tumor growth rate and breast density on the lowered performance of screening mammography in young women compared to older women.

METHODS

We estimated age-specific tumor volume doubling times (TVDT) and mammographic tumor size detection thresholds (DT). DT served as a measure of breast density. Age-specific DT and TVDT estimates were derived using a computer screening model that was calibrated to SEER breast cancer incidence and tumor sizes data from Breast Cancer Surveillance Consortium (BCSC). We simulated a 1960 birth cohort wherein women ages 50 to 69 years undergo annual screening and women ages 40 to 49 undergo one of three screening schedules: no screening, annual screening and biennial screening. We considered four scenarios for the TVDT and DT assigned to women ages 40-49 years. By evaluating the relative differences in the program sensitivity across these scenarios, we were able to quantify the relative contributions of TVDT and DT on the lowered screening performance for younger women compared to older women. We also computed the excess odds in each scenario of a woman having an interval cancer associated with being screened between the ages of 40-49 years compared with being screened between the ages of 50-69 years.

RESULTS

The relative contributions of DT and TVDT in annual screening to the lowered program sensitivity in women 40 to 49 years, compared to women 50 to 69 years, are 77% and 20%, respectively. Greater breast density explained 83.8% of the excess odds while rapid tumor growth explained only 5.1%. For biennial screening, the estimated relative contributions of DT and TVDT are 75% and 26%. Greater breast density and rapid tumor growth explained 77.5% and 30.6% of the excess odds, respectively.

CONCLUSIONS

Greater breast density is the dominant factor in annual and biennial screening for the lowered performance of screening among women 40 to 49 years old, compared to women 50 to 69 years old. Rapid tumor growth makes a larger contribution to the lower program sensitivity in biennial screening than it makes in annual screening. These results underscore the importance of continued efforts to improve imaging performance in young women with mammographically dense breast tissue. Such technological improvements should yield a greater increase in mammography sensitivity when comparing annual to biennial screening in younger women.