In Reply Dr Jatoi suggests that a reduction in the incidence of ER-negative breast cancer over the past decades could have contributed to the decline in breast cancer mortality observed in SEER between 1975 and 2019. Indeed, a decline in cancer incidence can have a primary role in decline of cancer-specific mortality, as in the case of lung cancer.¹ Similarly, a change in the composition of molecular subtypes among people diagnosed with incident breast cancer could affect mortality rates and even decrease mortality if the subtype with the higher mortality rate became less prevalent.

As Jatoi notes, in our study² we did not estimate what proportion of the decline in breast cancer mortality over time was attributable to changes in breast cancer incidence. Our objective was to quantify the relative changes in mortality reduction attributable to screening and treatment interventions while controlling for changes in mortality rates that could be attributed to changes in incidence rates. The CISNET models estimated annual breast cancer age-adjusted mortality rates in the absence and presence of modeled interventions by subtype and by calendar year. The reported 58% reduction in age-adjusted breast cancer mortality in 2019 is relative to the estimated mortality in 2019 had there been no screening or treatment improvements since 1975.

Each CISNET model differs in its approach to modeling incidence in the absence of screening, but all are designed to match observed overall SEER incidence curves and generate outputs approximating observed subtype-specific incidence data (Figure). While the extent to which the models reproduce a potential decline in ER-negative breast cancer incidence differs, each model found comparable estimates of overall and subtype-specific mortality reduction in 2019 (Table 1 in the article²).

Mortality reduction can be described with different measures. The 58% reduction in breast cancer mortality we report reflects the difference between 2 modeled scenarios in 2019, one with screening and treatment advances since 1975 and one without. Jatoi is interested in mortality reduction over time, and this observed reduction is 44% (from 48 deaths per 100 000 women in 1975 to 27 deaths per 100 000 in 2019, age-adjusted to the 2000 population). The change in mortality over time is affected by factors other than screening and treatment improvements, likely including changes in subtype-specific incidence. We agree that leveraging the models to decipher the factors that affect the absolute breast cancer mortality rates over time, in addition to a given calendar year as reported in our study, would be a worthy pursuit.

Corresponding Author: Sylvia K. Plevritis, PhD, Stanford University School of Medicine, James H. Clark Center, 318 Campus Dr, Stanford, CA 94305-5405 (sylvia.plevritis@stanford.edu).

Published Online: April 25, 2024. doi:10.1001/jama.2024.5482

Conflict of Interest Disclosures: Dr Caswell-Jin reported receiving grants from the National Cancer Institute during the conduct of the study and grants from Effector Therapeutics, Novartis, and QED Therapeutics. Dr Plevritis reported receiving grants from the National Institutes of Health during the conduct of the study. No other disclosures were reported.