Predictors of competing mortality to invasive breast cancer incidence in the Canadian National Breast Screening study

AbstractBACKGROUNDThe benefits of mammography screening have been controversial, with conflicting findings from various studies.METHODSWe hypothesize that unmeasured heterogeneity in tumor aggressiveness underlies these conflicting results. Based on published data from the Canadian National Breast Screening Study (CNBSS), we develop and parameterize an individual-based mechanistic model for breast cancer incidence and mortality that tracks five stages of breast cancer progression and incorporates the effects of age on breast cancer incidence and all-cause mortality.RESULTSThe model accurately reproduces the reported outcomes of the CNBSS. By varying parameters, we predict that the benefits of mammography depend on the effectiveness of cancer treatment and tumor.CONCLUSIONSIn particular, patients with the most rapidly growing or potentially largest tumors have the highest benefit and least harm from the screening, with only a relatively small effect of age. However, the model predicts that confining mammography populations with a high risk of acquiring breast cancer increases the screening benefit only slightly compared with the full population.

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The randomized trial of mammography screening that was not—A cautionary tale

Journal of Medical Screening ◽

10.1177/09691413211059461 ◽

2021 ◽

pp. 096914132110594

Author(s):

Martin J Yaffe ◽

Jean M. Seely ◽

Paula B. Gordon ◽

Shushiela Appavoo ◽

Daniel B. Kopans

Keyword(s):

Breast Cancer ◽

Breast Screening ◽

Clinical Breast Examination ◽

Control Group ◽

Multiple Indicators ◽

National Breast ◽

Breast Examination ◽

Screening Study ◽

Clinical Breast ◽

And Performance

Two randomized trials were conducted in Canada in the 1980s to test the efficacy of breast cancer screening. Neither of the trials demonstrated benefit. Concerns were raised regarding serious errors in trial design and conduct. Here we describe the conditions that could allow subversion of randomization to occur and the inclusion of many symptomatic women in a screening trial. We examine anomalies in data where the balance would be expected between trial arms. “Open book” randomization and performance of clinical breast examination on all women before allocation to a trial arm allowed women with palpable findings to be mis-randomized into the mammography arm. Multiple indicators raising suspicion of subversion are present including a large excess in poor-prognosis cancers in the mammography trial arm at prevalence screen. Personnel described shifting of women from the control group into the mammography group. There is compelling evidence of subversion of randomization in Canadian National Breast Screening Study. Mis-randomization of even a few women with advanced breast cancer could markedly affect measured screening efficacy. The Canadian National Breast Screening Study trials should not influence breast screening policies.

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