Highlight
– Missing the mammography screening immediately prior to breast cancer diagnosis leads to larger, more advanced tumors and worse breast cancer-specific survival.
– Nonparticipation in the immediate past screening correlates with increased risk of lymph node involvement and distant metastases.
– Tumor receptor profiles differ minimally except for a lower likelihood of estrogen receptor-negative tumors in nonparticipants.
– The association between past screening nonattendance and survival is mediated by tumor characteristics, underscoring delayed detection as a critical factor.
– Advancing mammography invitation dates may be a strategy to improve early detection and outcomes in this population.
Study Background and Disease Burden
Breast cancer is the most commonly diagnosed cancer among women globally and a leading cause of cancer mortality. Mammography screening programs have demonstrated significant impact in reducing breast cancer mortality by enabling the detection of malignancies at earlier, more treatable stages. However, the extent to which nonparticipation in mammography screening impacts the characteristics of screen-detected breast cancers (SDBCs) and subsequent survival remains understudied. Specifically, whether women who missed the screening round immediately before diagnosis experience clinically meaningful delays in detection, resulting in more advanced disease and poorer outcomes, is a critical knowledge gap that this study addresses.
Study Design
This is a prospective, register-based cohort study conducted in Stockholm, Sweden, encompassing all women diagnosed with screen-detected breast cancer between January 1, 1995, and February 28, 2020, with follow-up until December 31, 2022. The analysis was performed from November 5, 2023, to May 27, 2024. The exposure under investigation was nonparticipation in the mammography screening immediately prior to the diagnostic screening round that detected cancer. The main outcomes measured included tumor characteristics—tumor size, lymph node involvement, metastasis, receptor status (estrogen receptor [ER], progesterone receptor [PR], ERBB2/HER2 status)—and breast cancer-specific survival.
Key Findings
The study population consisted of 8602 women with SDBC with a median age of 61 years (IQR 55-66). Of these, 1482 women (17.2%) had not attended the immediate past screening prior to the diagnostic round.
Compared with women who participated in the prior screening, nonparticipants had significantly larger tumors (≥20 mm) with an adjusted odds ratio (AOR) of 1.55 (95% CI, 1.37-1.76). They also demonstrated increased lymph node involvement (AOR 1.28, 95% CI, 1.12-1.45) and markedly higher likelihood of distant metastasis (AOR 4.64, 95% CI, 2.10-10.29). Regarding receptor status, nonparticipants were less likely to have ER-negative tumors (AOR 0.74, 95% CI, 0.60-0.92), while PR and ERBB2 status showed no significant differences.
Survival analysis revealed poorer breast cancer-specific survival in women who missed the immediate past screening with an adjusted hazard ratio (AHR) of 1.33 (95% CI, 1.08-1.65). Notably, when adjusting for tumor characteristics, the survival difference was no longer significant (AHR 1.11, 95% CI, 0.89-1.38), indicating that the worse outcome is primarily attributable to delayed tumor detection and progression rather than intrinsic tumor biology.
No significant associations were observed between nonparticipation in the second-to-last screening and tumor characteristics or advanced stage tumors, implying the critical influence of the most recent screening round prior to diagnosis.
Expert Commentary
This robust, long-term cohort study leverages comprehensive registry data to underscore the clinically relevant impact of screening adherence on breast cancer outcomes. The findings reinforce that missing mammography screening leads to delayed detection, larger tumor burden, and increased metastasis, which subsequently worsen prognosis. The observation that survival differences dissipate after adjustment for tumor characteristics strengthens the case for early detection being key to improved outcomes.
These results are congruent with established breast cancer screening evidence, yet highlight the nuanced impact of missing just one screening interval in an organized program. Limitations include potential unmeasured confounding variables such as comorbidities or socio-economic determinants affecting participation and outcomes. The findings may primarily apply to settings with systematic screening programs similar to Sweden.
Given the magnitude of tumor advancement associated with missing a single screening, practical interventions to enhance participation or reduce screening intervals for those who missed the prior round warrant consideration. Translational research efforts may also investigate personalized screening schedules or alternate imaging modalities for high-risk nonparticipants.
Conclusion
This study provides compelling evidence that nonparticipation in the mammography screening immediately prior to breast cancer diagnosis leads to delayed detection, resulting in more advanced tumor characteristics and worse breast cancer-specific survival. These findings emphasize the imperative of maintaining consistent screening attendance to achieve optimal early detection. Future investigations should focus on identifying effective strategies to engage nonparticipants and evaluate whether advancing the timing of subsequent screening invitations could mitigate delays and improve clinical outcomes. Tailored interventions targeting screening adherence could substantially reduce breast cancer morbidity and mortality within population screening programs.
References
1. Mao X, He W, Tapia J, Holowko N, Bergqvist J, Humphreys K, Czene K. Screen-Detected Breast Cancer Outcomes by Mammography Participation in Immediate Past Screening. JAMA Netw Open. 2025 Oct 1;8(10):e2535330. doi:10.1001/jamanetworkopen.2025.35330. PMID: 41042510.
2. Duffy SW, Agbaje OF, Teh R, et al. Mammographic screening reduces rates of advanced and fatal breast cancers: results in 549,091 women. Cancer. 2020;126(16):3729-3735.
3. Broeders M, Moss S, Nyström L, et al. The impact of mammographic screening on breast cancer mortality in Europe: a review of observational studies. J Med Screen. 2012;19 Suppl 1:14-25.
4. Pace LE, Keating NL. A systematic assessment of benefits and risks to guide breast cancer screening decisions. JAMA. 2014;311(13):1327-1335.