Survival among women diagnosed with screen-detected or interval breast cancer classified as true, minimal signs, or missed through an informed radiological review

Abstract

Objectives “True” breast cancers, defined as not being visible on prior screening mammograms, are expected to be more aggressive than “missed” cancers, which are visible in retrospect. However, the evidence to support this hypothesis is limited. We compared the risk of death from any cause for women with true, minimal signs, and missed invasive screen-detected (SDC) and interval breast cancers (IC). Methods This nation-wide study included 1022 SDC and 788 IC diagnosed through BreastScreen Norway during 2005–2016. Cancers were classified as true, minimal signs, or missed by five breast radiologists in a consensus-based informed review of prior screening and diagnostic images. We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of death from any cause associated with true, minimal signs, and missed breast cancers, adjusting for age at diagnosis, histopathologic tumour diameter and grade, and subtype. Separate models were created for SDC and IC. Results Among SDC, 463 (44%) were classified as true and 242 (23%) as missed; among IC, 325 (39%) were classified as true and 235 (32%) missed. Missed SDC were associated with a similar risk of death as true SDC (HR = 1.20, 95% CI (0.49, 2.46)). Similar results were observed for missed versus true IC (HR = 1.31, 95% CI (0.77, 2.23)). Conclusions We did not observe a statistical difference in the risk of death for women diagnosed with true or missed SDC or IC; however, the number of cases reviewed and follow-up time limited the precision of our estimates. Key Points • An informed radiological review classified screen-detected and interval cancers as true, minimal signs, or missed based on prior screening and diagnostic mammograms. • It has been hypothesised that true cancers, not visible on the prior screening examination, may be more aggressive than missed cancers. • We did not observe a statistical difference in the risk of death from any cause for women with missed versus true screen-detected or interval breast cancers.

True and Missed Interval Cancer in Organized Mammographic Screening: A Retrospective Review Study of Diagnostic and Prior Screening Mammograms

“…Further, studies have identified genetic or molecular differences between the screen-detected and interval cancer, though these differences have been less marked or disappeared after adjusting for confounders as age, mammographic density and histologic type and grade (192,213,214). The worse survival for interval cancer persists even after adjustment for histopathological tumor characteristics (195,196,215,216). Thus, to improve detection of "killing cancers" and hence the mortality rates from breast cancer, a focus on reduction of interval cancer rates seems reasonable.…”

Risk Factors and Mortality Among Women With Interval Breast Cancer vs Screen-Detected Breast Cancer

“… 5 , 13 , 34 , 35 However, recent studies have not reported differences in long-term survival between SBCs and IBCs. 36 One study reported that except for the slightly larger size of IBC, the tumor characteristics of SBC and IBC were comparable. 37 Because our population-based screening study could not compare the tumor characteristics of IBC and SBC, further hospital-based studies with available tumor information should be conducted.…”

“…The reasons for lower survival rates of IBC (<1 year) compared with SBC have been suggested to be greater tumor size, more aggressive nature (eg, more lymph node involvement), and a higher proportion of lobular histologic characteristics . However, recent studies have not reported differences in long-term survival between SBCs and IBCs . One study reported that except for the slightly larger size of IBC, the tumor characteristics of SBC and IBC were comparable .…”

Evaluating cancer screening programs using survival analysis

“…Parametric models can be used to correct for lead time bias (Abrahamsson et al., 2020; Chen et al., 2012; Duffy et al., 2008; Lee et al., 2018; Mahnken et al., 2008; Walter & Stitt, 1987; Wu et al., 2007) and to reduce length time bias (Chen et al., 2012; Cucchetti et al., 2016; Hofvind et al., 2016; Mahnken et al., 2008). Some authors tried to reduce length time bias by using other control groups (Allgood et al., 2011; Kalager et al., 2009; Lawrence et al., 2009; Tsuruda et al., 2021; Walter & Stitt, 1987). However, to our knowledge, no existing approach can fully avoid the three biases.…”