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Background While knowledge and risk perception have been associated with screening for second primary cancer (SPC), there are no clinically useful indicators to identify who is at risk of not being properly screened for SPC. We investigated whether the mode of primary cancer detection (i.e. screen-detected vs. non-screen-detected) is associated with subsequent completion of all appropriate SPC screening in cancer survivors. Methods Data were collected from cancer patients treated at the National Cancer Center and nine regional cancer centers across Korea. A total of 512 cancer survivors older than 40, time since diagnosis more than 2 years, and whose first primary cancer was not advanced or metastasized were selected. Multivariate logistic regression was used to examine factors, including mode of primary cancer detection, associated with completion of all appropriate SPC screening according to national cancer screening guidelines. Results Being screen-detected for their first primary cancer was found to be significantly associated with completion of all appropriate SPC screening (adjusted odds ratio, 2.13; 95% confidence interval, 1.36–3.33), after controlling for demographic and clinical variables. Screen-detected cancer survivors were significantly more likely to have higher household income, have other comorbidities, and be within 5 years since diagnosis. Conclusions The mode of primary cancer detection, a readily available clinical information, can be used as an indicator for screening practice for SPC in cancer survivors. Education about the importance of SPC screening will be helpful particularly for cancer survivors whose primary cancer was not screen-detected.

Background Breast magnetic resonance imaging (MRI) is the most sensitive imaging method for breast cancer detection and is therefore offered as a screening technique to women at increased risk of developing breast cancer. However, mammography is currently added from the age of 30 without proven benefits. The purpose of this study is to investigate the added cancer detection of mammography when breast MRI is available, focusing on the value in women with and without BRCA mutation, and in the age groups above and below 50 years. Methods This retrospective single-center study evaluated 6553 screening rounds in 2026 women at increased risk of breast cancer (1 January 2003 to 1 January 2014). Risk category ( BRCA mutation versus others at increased risk of breast cancer), age at examination, recall, biopsy, and histopathological diagnosis were recorded. Cancer yield, false positive recall rate (FPR), and false positive biopsy rate (FPB) were calculated using generalized estimating equations for separate age categories (< 40, 40–50, 50–60, ≥ 60 years). Numbers of screens needed to detect an additional breast cancer with mammography (NSN) were calculated for the subgroups. Results Of a total of 125 screen-detected breast cancers, 112 were detected by MRI and 66 by mammography: 13 cancers were solely detected by mammography, including 8 cases of ductal carcinoma in situ. In BRCA mutation carriers, 3 of 61 cancers were detected only on mammography, while in other women 10 of 64 cases were detected with mammography alone. While 77% of mammography-detected-only cancers were detected in women ≥ 50 years of age, mammography also added more to the FPR in these women. Below 50 years the number of mammographic examinations needed to find an MRI-occult cancer was 1427. Conclusions Mammography is of limited added value in terms of cancer detection when breast MRI is available for women of all ages who are at increased risk. While the benefit appears slightly larger in women over 50 years of age without BRCA mutation, there is also a substantial increase in false positive findings in these women.

Background BreastScreen Australia, the population mammographic screening program for breast cancer, uses two-view digital screening mammography ± ultrasound followed by percutaneous biopsy to detect breast cancer. Secondary breast imaging for further local staging, not performed at BreastScreen, may identify additional clinically significant breast lesions. Staging options include further mammography, bilateral ultrasound, and/or contrast-based imaging (CBI) [magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM)]. CBI for local staging of screen-detected cancer was introduced at an academic hospital breast service in Melbourne, VIC, Australia. We report findings for otherwise occult disease and resulting treatment changes. Material and methods Patients staged using CEM between November 2018 and April 2022 were identified from hospital records. Data were extracted from radiology, pathology, and breast unit databases. CEM-detected abnormalities were documented as true positive (TP) for invasive cancer or ductal carcinoma in situ (DCIS), or otherwise false positive (FP). The impact on surgical decisions was assessed. Results Of 202 patients aged 44–84 years, 60 (30%) had 74 additional findings [34 (46%) TP, 40 (54%) FP]. These were malignant in 29/202 (14%) patients (79% invasive cancers, 21% DCIS). CEM resulted in surgical changes in 43/202 (21%) patients: wider resection (24/43), conversion to mastectomy (6/43), contralateral breast surgery (6/43), additional ipsilateral excision (5/43), and bracketing (2/43). Additional findings were more common for patients with larger index lesions and for invasive cancer, but there was no significant variation by age, breast density, or index lesion grade. Conclusions CEM for local staging of screen-detected breast cancers identified occult malignancy in 14% of patients. CEM improves local staging and may facilitate appropriate management of screen-detected breast cancers.

The faecal immunochemical test (FIT) has been increasingly used for organised colorectal cancer (CRC) screening. We assessed the impact of a six-year existing FIT screening programme in Flanders (Belgium) on CRC incidence, mortality and survival. The Flemish CRC screening programme started in 2013, targeting individuals aged 50–74 years. Joinpoint regression was used to investigate trends of age-standardised CRC incidence and mortality among individuals aged 50–79 years (2004–2019). Their 5-year relative survival was calculated using the Ederer II method. We found that FIT screening significantly reduced CRC incidence, especially that of advanced-stage CRCs (69.8/100,000 in 2012 vs. 51.1/100,000 in 2019), with a greater impact in men. Mortality started to decline in men two years after organised screening implementation (annual reduction of 9.3% after 2015 vs. 2.2% before 2015). The 5-year relative survival was significantly higher in screen-detected (93.8%) and lower in FIT non-participant CRCs (61.9%) vs. FIT interval cancers and CRCs in never-invited cases (67.6% and 66.7%, respectively). Organised FIT screening in Flanders clearly reduced CRC incidence (especially advanced-stage) and mortality (in men, but not yet in women). Survival is significantly better in screen-detected cases vs. CRCs in unscreened people. Our findings support the implementation of FIT organised screening and the continued effort to increase uptake.

Purpose Screen-detected unilateral non-palpable breast cancer (NPBC) shows favorable prognosis, whereas bilateral breast cancer (BBC), especially synchronous BBC (SBBC) manifests worse survival than unilateral breast cancer (BC). It remains unclear whether screen-detected bilateral NPBC has compromised survival and requires intensified treatment or favorable prognosis and needs de-escalating therapy. Methods From 2003 to 2017, 1,075 consecutive NPBC patients were retrospectively reviewed. There were 988 patients with unilateral NPBC (UniNPBC), and 87 patients with ipsilateral NPBC + any contralateral BC [(N + AnyContra) PBC], including 32 patients with bilateral NPBC (BiNPBC) and 55 patients with ipsilateral NPBC + contralateral palpable cancer [(N + Contra) PBC]. Median follow-up time was 91 (48–227) months. Clinicopathological characteristics were compared between UniNPBC and BBC, whereas relapse-free survival (RFS) and overall survival (OS) among BBC subgroups. RFS and OS factors of BBC were identified. Results Compared to UniNPBC, patients with screen-detected bilateral BC had more invasive (85.1%, 74.8%), ER negative (26.4%, 17.1%), PR negative (36.8%, 23.5%), triple-negative (21.6%, 8.5%) BC as well as less breast conserving surgery (17.2%, 32.4%), radiotherapy (13.8%, 32.0%) and endocrine therapy (71.3%, 83.9%). 10 year RFS and OS rates of (N + AnyContra) PBC (72.8%, 81.5%), (N + Contra) PBC (60.6%, 73.9%), and synchronous (N + Contra) PBC (58.1%, 70.1%) were significantly compromised compared to UniNPBC (91.0%, 97.2%). RFS factors of BBC included pN3 ( p  = 0.048), lymphovascular invasion ( p  = 0.008) and existence of contralateral palpable interval BC ( p  = 0.008), while the OS relevant factor was pN3 ( p  = 0.018). Conclusion Screen-detected bilateral NPBC including SynBiNPBC and MetaBiNPBC showed good prognosis as UniNPBC so that the therapy of BiNPBC could be de-escalated and optimized according to UniNPBC. Contrarily, screen-detected ipsilateral NPBC with contralateral palpable BC [(N + Contra) PBC] manifested unfavorable survival worse than UniNPBC and synchronous (N + Contra) PBC had the worst survival among all subgroups, implying that these were actually bilateral interval BC and required intensified treatment.

PurposeStudies have shown that screen detection by national screening programs is independently associated with better prognosis of breast cancer. The aim of this study is to evaluate the association between tumor biology according to the 70-gene signature (70-GS) and survival of patients with screen-detected and interval breast cancers.MethodsAll Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041/BIG3-04) accrued 2007–2011, who participated in the national screening program (biennial screening, ages 50–75) were included (n = 1102). Distant Metastasis-Free Interval (DMFI) was evaluated according to the 70-GS for patients with screen-detected (n = 754) and interval cancers (n = 348).ResultsPatients with screen-detected cancers had 8-year DMFI rates of 98.2% for 70-GS ultralow-, 94.6% for low-, and 93.8% for high-risk tumors (p = 0.4). For interval cancers, there was a significantly lower 8-year DMFI rate for patients with 70-GS high-risk tumors (85.2%) compared to low- (92.2%) and ultralow-risk tumors (97.4%, p = 0.0023). Among patients with 70-GS high-risk tumors, a significant difference in 8-year DMFI rate was observed between interval (85.2%, n = 166) versus screen-detected cancers (93.8%, n = 238; p = 0.002) with a HR of 2.3 (95%CI 1.2–4.4, p = 0.010) adjusted for clinical-pathological characteristics and adjuvant systemic treatment.ConclusionAmong patients with 70-GS high-risk tumors, a significant difference in DMFI was observed between screen-detected and interval cancers, suggesting that method of detection is an additional prognostic factor in this subgroup and should be taken into account when deciding on adjuvant treatment strategies.

Background Case–control studies show that mammographic density is a better risk factor when defined at higher than conventional pixel-brightness thresholds. We asked if this applied to interval and/or screen-detected cancers. Method We conducted a nested case–control study within the prospective Melbourne Collaborative Cohort Study including 168 women with interval and 422 with screen-detected breast cancers, and 498 and 1197 matched controls, respectively. We measured absolute and percent mammographic density using the Cumulus software at the conventional threshold ( Cumulus ) and two increasingly higher thresholds ( Altocumulus and Cirrocumulus , respectively). Measures were transformed and adjusted for age and body mass index (BMI). Using conditional logistic regression and adjusting for BMI by age at mammogram, we estimated risk discrimination by the odds ratio per adjusted standard deviation (OPERA), calculated the area under the receiver operating characteristic curve (AUC) and compared nested models using the likelihood ratio criterion and models with the same number of parameters using the difference in Bayesian information criterion (ΔBIC). Results For interval cancer, there was very strong evidence that the association was best predicted by Cumulus as a percentage (OPERA = 2.33 (95% confidence interval (CI) 1.85–2.92); all ΔBIC > 14), and the association with BMI was independent of age at mammogram. After adjusting for percent Cumulus , no other measure was associated with risk (all P  > 0.1). For screen-detected cancer, however, the associations were strongest for the absolute and percent Cirrocumulus measures (all ΔBIC > 6), and after adjusting for Cirrocumulus , no other measure was associated with risk (all P  > 0.07). Conclusion The amount of brighter areas is the best mammogram-based measure of screen-detected breast cancer risk, while the percentage of the breast covered by white or bright areas is the best mammogram-based measure of interval breast cancer risk, irrespective of BMI. Therefore, there are different features of mammographic images that give clinically important information about different outcomes.

Objective Breast cancer screening aims to identify cancers in early stages when prognosis is better and treatments less invasive. We describe inter- and intra-provincial variation in the percentage of screen-detected cases under publicly funded healthcare systems and factors related to having screen- vs non-screen-detected breast cancer across five Canadian provinces. Methods Women aged 40+ diagnosed with incident breast cancer from 2007 to 2012 in five Canadian provinces were identified from their respective provincial cancer registries. Standardized provincial datasets were created linking screening, health administrative, and claims data. Province-specific logistic regression models were used to evaluate the association of demographic and healthcare utilization factors in each province with the odds of screen-detected cancer. Results There was significant inter- and intra-provincial variation by age. Screen detection ranged from 42% to 52% in ages 50–69 but women aged 50–59 had approximately 4–8% lower screen detection than those aged 60–69 in all provinces. Screening associations with income quintile and rurality varied across provinces. Those least likely to be screen-detected within a province were consistently in the lowest income quintile; OR ranged from 0.62–0.89 relative to highest income quintile/urban patients aged 50–69. Lack of visits to primary care 30 months prior to diagnosis was also consistently associated with lower odds of screen detection (OR range, 0.37–0.76). Conclusion Breast cancer screen detection rates in the Canadian provinces examined are relatively high. Associations with income-rurality indicate a need for greater attention and/or targeted outreach to specific communities and/or provincial regions to improve access to breast cancer screening services intra-provincially.

Background BRCA mutation carriers have an elevated lifetime breast cancer risk and remain at risk for interval cancer development. We sought to compare BRCA mutation carriers with screen-detected versus interval breast cancers. Methods Women with a known BRCA mutation prior to a breast cancer diagnosis were identified. Clinical and pathologic factors, and imaging within 18 months of diagnosis were compared among screen-detected versus interval cancers. Interval cancers were those detected by physical exam among women undergoing regular screening. Results Of 124 breast cancers, 92 were screen and 22 clinically detected, of which 11 were interval cancers among regular screeners, and 10 were incidentally found on prophylactic mastectomy. Women with interval cancers were younger, had lower body mass indexes, and were more likely to be Black than those with screen-detected cancers ( p  < 0.05). Interval cancers were all invasive, larger, more likely to be node positive, and more likely to require axillary lymph node dissection and chemotherapy ( p  < 0.05). No significant differences were seen by BRCA mutation, mammographic density, MRI background parenchymal enhancement, tumor grade, or receptor status between cohorts. Women screened with both mammogram and MRI had significantly lower proportions of interval cancers compared to women screened with only mammogram or MRI alone ( p  < 0.05). Conclusions Interval breast cancers among BRCA mutation carriers have worse clinicopathologic features than screen-detected tumors, and require more-aggressive medical and surgical therapy. Imaging with mammogram and MRI is associated with lower interval cancer development and should be utilized among this high-risk population.

ObjectivesThe randomized controlled trial comparing digital breast tomosynthesis and synthetic 2D mammograms (DBT + SM) versus digital mammography (DM) (the To-Be 1 trial), 2016–2017, did not result in higher cancer detection for DBT + SM. We aimed to determine if negative cases prior to interval and consecutive screen-detected cancers from DBT + SM were due to interpretive error.MethodsFive external breast radiologists performed the individual blinded review of 239 screening examinations (90 true negative, 39 false positive, 19 prior to interval cancer, and 91 prior to consecutive screen-detected cancer) and the informed consensus review of examinations prior to interval and screen-detected cancers (n = 110). The reviewers marked suspicious findings with a score of 1–5 (probability of malignancy). A case was false negative if ≥ 2 radiologists assigned the cancer site with a score of ≥ 2 in the blinded review and if the case was assigned as false negative by a consensus in the informed review.ResultsIn the informed review, 5.3% of examinations prior to interval cancer and 18.7% prior to consecutive round screen-detected cancer were considered false negative. In the blinded review, 10.6% of examinations prior to interval cancer and 42.9% prior to consecutive round screen-detected cancer were scored ≥ 2. A score of ≥ 2 was assigned to 47.8% of negative and 89.7% of false positive examinations.ConclusionsThe false negative rates were consistent with those of prior DM reviews, indicating that the lack of higher cancer detection for DBT + SM versus DM in the To-Be 1 trial is complex and not due to interpretive error alone.Critical relevance statementThe randomized controlled trial on digital breast tomosynthesis and synthetic 2D mammograms (DBT) and digital mammography (DM), 2016–2017, showed no difference in cancer detection for the two techniques. The rates of false negative screening examinations prior to interval and consecutive screen-detected cancer for DBT were consistent with the rates in prior DM reviews, indicating that the non-superior DBT performance in the trial might not be due to interpretive error alone.Key points• Screening with digital breast tomosynthesis (DBT) did not result in a higher breast cancer detection rate compared to screening with digital mammography (DM) in the To-Be 1 trial.• The false negative rates for examinations prior to interval and consecutive screen-detected cancer for DBT were determined in the trial to test if the lack of differences was due to interpretive error.• The false negative rates were consistent with those of prior DM reviews, indicating that the lack of higher cancer detection for DBT versus DM was complex and not due to interpretive error alone.