Breast cancer subtype and screening sensitivity in the Quebec Mammography Screening Program

Abstract

Objective In mammography screening, interval cancers present a problem. The metric ‘screening sensitivity’ monitors both how well a programme detects cancers and avoids interval cancers. To our knowledge, the effect of breast cancer surrogate molecular subtypes on screening sensitivity has never been evaluated. We aimed to measure the 2-year screening sensitivity according to breast cancer subtypes. Methods We studied 734 women with an invasive breast cancer diagnosed between 2003 and 2007 after participating in one regional division of Quebec’s Mammography Screening Program. They represented 83% of all participating women with an invasive BC diagnosis in that region for that period. Tumours were categorized into ‘luminal A-like’, ‘luminal B-like’, ‘triple-negative’ and ‘HER2-positive’ subtypes. We used logistic regression and marginal standardization to estimate screening sensitivity, sensitivity ratios (SR) and sensitivity differences. We also assessed the mediating effect of grade. Results Adjusted 2-year screening sensitivity was 75.4% in luminal A-like, 66.1% in luminal B-like, 52.9% in triple-negative and 45.3% in HER2-positive, translating into sensitivity ratios of 0.88 (95% confidence interval [CI] = 0.78–0.98) for luminal B-like, 0.70 (CI = 0.56–0.88) for triple-negative and 0.60 (CI = 0.39–0.93) for HER2-positive, when compared with luminal A-like. Grade entirely mediated the subtype-sensitivity association for triple negative and mediated it partly for HER2-positive. Screening round (prevalent vs. incident) did not modify results. Conclusion There was substantial variation in screening sensitivity according to breast cancer subtypes. Aggressive phenotypes showed the lowest sensitivity, an effect that was mediated by grade. Tailoring screening according to women’s subtype risk factors might eventually lead to more efficient programs.

An analysis of screen-detected invasive cancers by grade in the English breast cancer screening programme: are we failing to detect sufficient small grade 3 cancers?

“…Crucially, this validation suggests that our assumptions are reasonable. Similar results relating to biomarkers are reported from a 2-year Canadian screening programme [9]. For prevalent screen data, we are suggesting that the rate of undetected (if we had the same sensitivity as for grade 1) small (< 15 mm) grade 3 invasive cancers is 1900 from 2,295,016 women which is 0.83 per 1000.…”

“…Relative sensitivity for small (< 15 mm) grade 2 and 3 cancers is lower at 42% and 26% respectively. Table 3 shows our estimation of relative sensitivity along with estimations of relative sensitivity from published information adapted from Porter et al [8] and Perron et al [9] showing some agreement and therefore that such an approach could be useful. [10].…”

“…Porter [8] found that most interval cancers (those clinically presenting between screens) are grade 3 or grade 2 and that only a small proportion of interval cancers are grade 1. Perron [9] has similarly shown that the sensitivity of screening in Quebec is lowest for the most aggressive phenotypes and that this effect is mediated by grade. This reinforces the STC message that at least 30% of the screen-detected grade 3 invasive cancers should be < 15 mm in diameter [10] when they are less likely to have nodal involvement.…”

Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation (PERSPECTIVE I&I)

“…To address these needs, we are conducting a pre-implementation study in >5000 women from Québec and Ontario, Canada. This study leverages the resources available through the existing screening programs including infrastructure, databases, links to primary care genetic clinics, and cancer registries [15,53,54]. Figure 3 provides an overview of data collection and follow-up, also described below.…”

MRI versus mammography plus ultrasound in women at intermediate breast cancer risk: study design and protocol of the MRIB multicentre randomized controlled trial

“…However, even for women who regularly adhere to a screening program, risk reduction brought about by Mx screening remains approximately 40% [3]. Such limited efficacy has been attributed not only to the intrinsic limitations of Mx but also to the highly variable biological characteristics of BC [4], as well as to women's individual characteristics such as age and breast density (BD). A high BD is not only an independent BC risk factor for both premenopausal and postmenopausal women [5,6], but also reduces Mx sensitivity (masking effect), resulting in an increased interval cancer rate [7][8][9].…”