Effects of screening and systemic adjuvant therapy on ER-specific US breast cancer mortality

Abstract

Background: Molecular characterization of breast cancer allows subtype-directed interventions. Estrogen receptor (ER) is the longest-established molecular marker.

Methods: We used six established population models with ER-specific input parameters on age-specific incidence, disease natural history, mammography characteristics, and treatment effects to quantify the impact of screening and adjuvant therapy on age-adjusted US breast cancer mortality by ER status from 1975 to 2000. Outcomes included stage-shifts and absolute and relative reductions in mortality; sensitivity analyses evaluated the impact of varying screening frequency or accuracy.

Results: In the year 2000, actual screening and adjuvant treatment reduced breast cancer mortality by a median of 17 per 100000 women (model range = 13-21) and 5 per 100000 women (model range = 3-6) for ER-positive and ER-negative cases, respectively, relative to no screening and no adjuvant treatment. For ER-positive cases, adjuvant treatment made a higher relative contribution to breast cancer mortality reduction than screening, whereas for ER-negative cases the relative contributions were similar for screening and adjuvant treatment. ER-negative cases were less likely to be screen-detected than ER-positive cases (35.1% vs 51.2%), but when screen-detected yielded a greater survival gain (five-year breast cancer survival = 35.6% vs 30.7%). Screening biennially would have captured a lower proportion of mortality reduction than annual screening for ER-negative vs ER-positive cases (model range = 80.2%-87.8% vs 85.7%-96.5%).

Conclusion: As advances in risk assessment facilitate identification of women with increased risk of ER-negative breast cancer, additional mortality reductions could be realized through more frequent targeted screening, provided these benefits are balanced against screening harms.

Figure 1.

Breast cancer mortality rate comparison of six model predictions to actual US rates for patients ages 30 to 79 at diagnosis from 1975 to 2000. Results include age-adjusted rates for all, estrogen receptor (ER)–positive and ER-negative breast cancer patients. ER-specific rates were calculated as the number of cases of that subtype divided by all women; in this manner, rates of both subtypes sum to the overall breast cancer rates. Actual US rates are derived from Surveillance, Epidemiology, and End Results (SEER) incidence–based mortality data. Unknown cases imputed assuming an 80/20 split between ER+ and ER- prevalence. SEER results by ER status are only shown from 1994 through 2000, before which ER status was not collected or largely unknown. ER = estrogen receptor.

Figure 2.

Predicted US overall and estrogen receptor (ER)–specific breast cancer mortality rates under counterfactual scenarios that include no screening and no adjuvant therapy, screening only, adjuvant therapy only, in comparison to screening and adjuvant treatment, for representative model (Model S). Results include age-adjusted rates for all, ER-positive and ER-negative breast cancer patients. ER-specific rates were calculated as the number of cases of that subtype divided by all women; in this manner, rates of both subtypes sum to the overall breast cancer rates. ER = estrogen receptor.