Association of Screening and Treatment With Breast Cancer Mortality by Molecular Subtype in US Women, 2000‒2012
All six simulation modeling groups for breast cancer participated in a project to determine the associations of screening and adjuvant treatment with reductions in US breast cancer mortality rates by molecular subtype (Plevritis et al., 2018). The results suggest that for women aged 30 to 79 years, advances in treatment (such as the use of new adjuvant therapies) were associated with greater estimated reductions in overall breast cancer mortality from 2000 to 2012 compared with advances in screening. The models attributed 63% (model range: 49‒74%) of the overall breast cancer mortality reduction to treatment, with only 37% (model range: 26‒51%) of the reduction associated with screening. Of this 63% associated with treatment, 31% was associated with chemotherapy; 27% with hormone therapy; and 4% with trastuzumab. These results varied by breast cancer molecular subtype.
Contribution of Screening and Treatment on Breast Cancer Trends
Prior model-based analyses published in the New England Journal of Medicine (Berry et al., 2005) and described as a landmark study, quantified the relative effects of screening mammography and adjuvant treatment at a population level. However, these effects had not been quantified by estrogen receptor (ER) status. Breast cancer is a heterogeneous disease defined by molecular subtypes that predict treatment response and clinical outcomes and ER is the longest-established molecular marker in use for breast cancer treatment planning. To quantify the effects of screening and adjuvant treatment on US breast cancer mortality trends by ER status from 1975 to 2000, the CISNET Breast Working Group updated the landmark analysis using ER-specific model inputs (Munoz et al., 2014). All six modeling groups projected greater absolute mortality declines in ER-positive cancers than among ER-negative cancers, consistent with observed trends. 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 cancers were less likely to be screen-detected than ER-positive cancers (35.1% vs. 51.2%), but when screen-detected, yielded a greater survival gain (five-year breast cancer survival = 35.6% vs. 30.7%).
A manuscript with analyses for 2000-2010 using ER and HER2-specific inputs and modeling newer adjuvant treatments including anthracycline-based regimens and taxanes, aromatase inhibitors for ER-positive breast cancers, and trastuzumab for HER-2 positive tumors, is currently under review.