**1. Introduction**

Early detection of breast cancer through screening mammography and advances in technology and treatments have led to improved breast cancer (BC) survival [1]. Technology improvements such as breast ultrasound and magnetic resonance imaging have also markedly improved the ability of radiologists to diagnose breast cancer and profound changes in treatment have contributed to a 46% reduction in breast cancer mortality since screening mammography began in 1989 in Canada [2]. Treatment advances for breast cancer may raise questions about the relative importance of screening. Yet despite these advances, BC is still expected to be responsible for a quarter of all new cancer diagnoses in Canadian women and 14% of all cancer deaths in women in 2022 [3]. BC is the leading cause of non-accidental death in women younger than 50, and 30% of life years lost to BC are among women diagnosed in their 40s [4].

Mammographic screening for women in their 40s is contentious. The Canadian Task Force on Preventive Health Care (CTFPHC) recommended against routine screening of women aged 40–49 in their 2011 and 2018 guidelines and suggested that care providers should engage in discussion with these patients around screening [5,6]. The eight randomised controlled trials (RCTs) considered in these guidelines were performed between

**Citation:** Wilkinson, A.N.; Billette, J.-M.; Ellison, L.F.; Killip, M.A.; Islam, N.; Seely, J.M. The Impact of Organised Screening Programs on Breast Cancer Stage at Diagnosis for Canadian Women Aged 40–49 and 50–59. *Curr. Oncol.* **2022**, *29*, 5627–5643. https://doi.org/10.3390/ curroncol29080444

Received: 23 June 2022 Accepted: 3 August 2022 Published: 9 August 2022

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1963 and 1991, prior to advances such as digital mammography and trastuzumab, and had screening intervals of up to 33 months [7–14]. Meta-analysis of these eight trials showed a BC mortality reduction of 15–18% for women 40–49 [15]. The Canadian National Breast Screening Study was the only trial that did not show a significant mortality reduction with screening [16]; however, the validity of randomisation and image quality in this trial have since been called into question [17,18]. A meta-analysis of the remaining seven trials showed a BC mortality reduction of 24% for the number of women invited to screen [19], and 29% for the combined five Swedish RCTs for women aged 40–49 at entry into screening [15].

Several observational studies exist which contribute valuable population-level insight and more accurately reflect actual screening practices, such as a yearly screening interval. The Pan Canadian trial involved 2.8 million women in Canadian screening programs over a 20-year period and showed a 44% BC mortality reduction in women aged 40–49 who were screened with mammography [20]. A similar rate of 41% reduction in mortality was seen in Sweden in 550,000 women after 10 years of participation in an organised screening program, as well as a 25% reduction in the rate of advanced cancers [21,22].

The goal of BC screening is to detect earlier, more treatable stages of BC. Although some studies postulate that the rate of advanced stage BC has not changed since the introduction of screening in the late 1980s [23–25], these studies have been criticised because tumor registry data were not linked to exposure to screening, and the annual increase in BC incidence of 1% from 1950 until 2001 was not accounted for [26–28]. It is clear that women in organised breast screening programs are more likely to have a lowerstage disease at diagnosis [29]. Early stage BC typically involves treatments with lower morbidity, including the decreased need for mastectomy, axillary dissection, chemotherapy, and radiation therapy, ultimately providing cost savings [30]. Stage-shift with screen detection has been shown to translate into survival benefits and is not merely a reflection of lead-time bias [31,32].

The relationship between breast cancer screening and overdiagnosis has garnered increasing attention, particularly given the improvements in treatments for breast cancer [33]. A recent review by Yaffe and Mainprize demonstrated that overdiagnosis is better-termed overdetection and may occur in the context of screening when cancers that are slow growing or indolent are detected and would not have surfaced clinically or caused the patient's death [34]. This may be an important harm from screening if treatment is not tailored to the affected individual. Using Canadian modelling data, Yaffe and Mainprize found that rates of overdetection were much lower than estimated by the CTFPHC and were more likely to occur in older women than younger women due to competing causes of death [34]. A very recent Belgian modelling study similarly confirmed that overdiagnosis was much more likely in older women and found that estimates of overdiagnosis were much more accurate with a follow-up of 10 years or more [35].

BC screening programs for women aged 40–49 are considered most effective when they are organised, (i.e., population-based) and when they include annual reminders [4,36]. Active recruitment is generally employed to achieve a target participation rate of 70%. Opportunistic programs where women are required to take an active role in arranging their screening have been shown to have significantly lower screening rates [37]. Annual screening is important as the growth of BC in premenopausal women is more rapid [38]. Younger women aged 40–49 are more likely to have dense breasts, which among other factors increase the risk of BC [39]. It has been shown that mammography in women with extremely dense breasts is more effective if it is performed yearly [40,41].

This study assesses the relationship between Canadian mammography screening practices for women aged 40–49 on the stage of BC at diagnosis in women aged 40–49 and 50–59 years using incidence data from the Canadian Cancer Registry (CCR) and screening information from the Canadian Community Health Survey (CCHS) as well as provincial and territorial screening practices. Variations in jurisdictional screening policies in Canada allow this unique opportunity to evaluate the impact of different programmatic screening policies on the stages of breast cancer at diagnosis in women 40–49 and 50–59 years old. To our knowledge, this work has not been performed before in Canada or elsewhere in another country.
