Analysis of Breast Cancer Mortality in the US-1975 to 2019

Abstract

Importance: Breast cancer mortality in the US declined between 1975 and 2019. The association of changes in metastatic breast cancer treatment with improved breast cancer mortality is unclear.

Objective: To simulate the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality.

Design, setting, and participants: Using aggregated observational and clinical trial data on the dissemination and effects of screening and treatment, 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models simulated US breast cancer mortality rates. Death due to breast cancer, overall and by estrogen receptor and ERBB2 (formerly HER2) status, among women aged 30 to 79 years in the US from 1975 to 2019 was simulated.

Exposures: Screening mammography, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer.

Main outcomes and measures: Model-estimated age-adjusted breast cancer mortality rate associated with screening, stage I to III treatment, and metastatic treatment relative to the absence of these exposures was assessed, as was model-estimated median survival after breast cancer metastatic recurrence.

Results: The breast cancer mortality rate in the US (age adjusted) was 48/100 000 women in 1975 and 27/100 000 women in 2019. In 2019, the combination of screening, stage I to III treatment, and metastatic treatment was associated with a 58% reduction (model range, 55%-61%) in breast cancer mortality. Of this reduction, 29% (model range, 19%-33%) was associated with treatment of metastatic breast cancer, 47% (model range, 35%-60%) with treatment of stage I to III breast cancer, and 25% (model range, 21%-33%) with mammography screening. Based on simulations, the greatest change in survival after metastatic recurrence occurred between 2000 and 2019, from 1.9 years (model range, 1.0-2.7 years) to 3.2 years (model range, 2.0-4.9 years). Median survival for estrogen receptor (ER)-positive/ERBB2-positive breast cancer improved by 2.5 years (model range, 2.0-3.4 years), whereas median survival for ER-/ERBB2- breast cancer improved by 0.5 years (model range, 0.3-0.8 years).

Conclusions and relevance: According to 4 simulation models, breast cancer screening and treatment in 2019 were associated with a 58% reduction in US breast cancer mortality compared with interventions in 1975. Simulations suggested that treatment for stage I to III breast cancer was associated with approximately 47% of the mortality reduction, whereas treatment for metastatic breast cancer was associated with 29% of the reduction and screening with 25% of the reduction.

Figure 1.. Modeling Overview of Breast Cancer Diagnosis and Metastatic Recurrence

A, Simulated events and interventions over time of a representative patient with breast cancer and metastatic recurrence. Triangle represents breast cancer diagnosis and diamond, metastatic recurrence. Interventions in blue: circles indicate screening; hexagon, stage I to III treatments; and squares, 4 representative metastatic treatments. B, Illustration of changes in metastatic treatment across multiple lines of therapy by calendar year (eTable 3 in Supplement 1). In 3 of the models (D, S, and W), benefits from multiple lines of metastatic treatments are applied sequentially based on time to progression from prior treatment and treatment options available at progression. When a clinical trial demonstrated an overall survival benefit of one therapy over a control therapy (rather than over placebo), the benefits (hazard ratios of overall survival) of each of those therapies were multiplied to determine the benefit of the new therapy. Model M instead applies a single hazard ratio intended to capture the benefit of all sequential lines of therapy at diagnosis of metastatic disease. AI indicates aromatase inhibitor; CDK4/6, cyclin-dependent kinase 4 and 6; ER, estrogen receptor; and T-DM1, trastuzumab emtansine. Asterisks indicate that the benefits of these treatments are multiplied to determine the benefit of that line of therapy. See the Methods section for an explanation of each of the methods (D, M, S, and W).

Figure 2.. Association of Cancer Control Interventions With US Breast Cancer Mortality Reduction Over Time

A, Model-estimated mean age-adjusted breast cancer mortality among women aged 30 to 79 years under various scenarios compared with observed breast cancer mortality from SEER from 1975 to 2019. The dashed line represents observed mortality (SEER data); solid lines represent model results. Model means are computed across all 4 models, equally weighted; individual model results are shown in eFigure 7 in Supplement 1. B, Model-estimated mean predicted components of cumulative breast cancer mortality reduction associated with screening, metastatic treatments, and stage I to III treatments from 1998 to 2019. All interventions are in addition to standard treatments available in 1975. Because local therapy was part of standard-of-care treatment for stage I to III disease in 1975, the benefit of screening occurs in the presence of standard local therapy. Model means are computed across all 4 models, equally weighted; individual model results are shown in eFigure 10 in Supplement 1. SEER indicates Surveillance, Epidemiology, and End Results Program.

Figure 3.. Estimated Breast Cancer–Specific Survival After Metastatic Recurrence and 5-Year Distant Recurrence-Free Survival by ER/ERBB2 Status

A, Model-estimated median breast cancer–specific survival after metastatic recurrence. Pertuzumab and trastuzumab emtansine were introduced for ERBB2+ subtypes in 2012. Model means are computed across all 4 models, equally weighted; individual model results are shown in eTable 6 in Supplement 1. B, Model-estimated mean 5-year distant recurrence-free survival. Trastuzumab was introduced for ERBB2+ subtypes in 2005. Model means are computed across all 4 models, equally weighted; individual model results are shown in eTable 7 in Supplement 1.