Vaccine-associated axillary lymphadenopathy with a focus on COVID-19 vaccines. / Impfassoziierte axilläre Lymphadenopathie mit Fokus auf COVID-19-Impfstoffe.

Axillary lymphadenopathy (LA) after COVID-19 vaccination is now known to be a common side effect. In these cases, malignancy cannot always be excluded on the basis of morphological imaging criteria.Narrative review for decision-making regarding control and follow-up intervals for axillary LA according to currently published research. This article provides a practical overview of the management of vaccine-associated LA using image examples and a flowchart and provides recommendations for follow-up intervals. A particular focus is on patients presenting for diagnostic breast imaging. The diagnostic criteria for pathological lymph nodes (LN) are explained.Axillary LA is a common adverse effect after COVID-19 vaccination (0.3-53%). The average duration of LA is more than 100 days. LA is also known to occur after other vaccinations, such as the seasonal influenza vaccine. Systematic studies on this topic are missing. Other causes of LA after vaccination (infections, autoimmune diseases, malignancies) should be considered for the differential diagnosis. If the LA persists for more than 3 months after COVID-19 vaccination, a primarily sonographic follow-up examination is recommended after another 3 months. A minimally invasive biopsy of the LA is recommended if a clinically suspicious LN persists or progresses. In the case of histologically confirmed breast cancer, a core biopsy without a follow-up interval is recommended regardless of the vaccination, as treatment appropriate to the stage should not be influenced by follow-up intervals. For follow-up after breast cancer, the procedure depends on the duration of the LA and the woman's individual risk of recurrence.Vaccination history should be well documented and taken into account when evaluating suspicious LN. Biopsy of abnormal, persistent, or progressive LNs is recommended. Preoperative staging of breast cancer should not be delayed by follow-up. The risk of false-positive findings is accepted, and the suspicious LNs are histologically examined in a minimally invasive procedure. · The vaccination history must be documented (vaccine, date, place of application).. · If axillary LA persists for more than 3 months after vaccination, a sonographic follow-up examination is recommended after 3 months.. · Enlarged LNs that are persistent, progressive in size, or are suspicious on control sonography should be biopsied.. · Suspicious LNs should be clarified before starting oncological therapy, irrespective of the vaccination status, according to the guidelines and without delaying therapy.. · Wilpert C, Wenkel E, Baltzer PA et al. Vaccine-associated axillary lymphadenopathy with a focus on COVID-19 vaccines. Fortschr Röntgenstr 2024; DOI 10.1055/a-2328-7536.

[Structured screening for sporadic breast cancer]. / Strukturierte Früherkennung des sporadischen Mammakarzinoms.

BACKGROUND: The aim of secondary prevention of breast cancer is to detect the disease at the earliest curable stage and thus to reduce breast cancer-specific mortality. To this end, the nationwide population-based mammography screening program (MSP) was set up in Germany in 2005 in addition to an interdisciplinary prevention project for high-risk groups. OBJECTIVE: Overview of the current state of the MSP, the upcoming age expansion, and potential further developments. MATERIAL AND METHODS: Narrative review article with topic-guided literature and data search. RESULTS: Approximately 50% of the 70,500 new cases of breast cancer that occur each year are related to the age group of the MSP. 10 years after introduction of the MSP, the incidence of advanced breast cancer stages and breast cancer-related mortality of the screening target group have steadily decreased by about one quarter, while no relevant trends were seen in the neighboring age groups at the population level. CONCLUSION: The MSP has effectively contributed to a reduction of breast cancer mortality. With the expansion of the age groups to 45-75 years, more women have access to structured, quality assured screening. With the use of advanced stratifications and diagnostics as well as artificial intelligence, the MSP could be further optimized.

Recommendations of the German Radiological Society's breast imaging working group regarding breast MRI. / Aktualisierung der Empfehlungen der AG Mammadiagnostik der Deutschen Röntgengesellschaft zur Durchführung der Mamma-MRT.

· Breast MRI is an essential part of breast imaging. · The recommendations for performing breast MRI have been updated. · A table provides a compact and quick overview. More detailed comments supplement the table.. · The "classic" breast MRI can be performed based on the recommendations. Tips for special clinical questions, such as implant rupture, mammary duct pathology or local lymph node status, are included.. ZITIERWEISE: · Wenkel E, Wunderlich P, Fallenberg E et al. Aktualisierung der Empfehlungen der AG Mammadiagnostik der Deutschen Röntgengesellschaft zur Durchführung der Mamma-MRT. Fortschr Röntgenstr 2024; DOI: 10.1055/a-2216-0782.

Breast cancer screening with digital breast tomosynthesis: Is independent double reading still required? / Brustkrebs-Screening mit digitaler Brust-Tomosynthese: Ist weiterhin eine unabhängige Doppelbefundung erforderlich?

PURPOSE: The European guidelines recommend independent double reading in mammography screening programs. The prospective randomized controlled trial TOSYMA tested the superiority of digital breast tomosynthesis and synthetic mammography (DBT+SM) over digital mammography (DM) for invasive breast cancer detection. This sub-analysis compares the true-positive readings of screening-detected breast cancers resulting from independent double readings in the two trial arms. MATERIALS AND METHODS: The 1:1 randomized TOSYMA trial was executed in 17 screening units between 07/2018 and 12/2020. This sub-analysis included 49,762 women in the test arm (DBT+SM) and 49,796 women in the control arm (DM). The true-positive reading results (invasive breast cancers and ductal carcinoma in situ) from 83 readers were determined and merged in a double reading result. RESULTS: DBT+SM screening detected 416 women with breast cancer and DM screening detected 306. Double readings of DBT+SM examinations led to a single true-positive together with a single false-negative result in 26.9 % of cancer cases (112/416), and in 22.2 % of cases (68/306) in the DM examinations. The cancer detection rate with discordant reading results was 2.3 per 1,000 women screened with DBT+SM and 1.4 per 1,000 with DM. Discordant reading results occurred most often for invasive breast cancers [DBT+SM 75.9 % (85/112), DM 67.6 % (46/68)], category T1 [DBT+SM 67.9 % (76/112), DM 55.9 % (38/68)], and category 4a [DBT+SM: 67.6 % (73/112); DM: 84.6 % (55/68)]. CONCLUSION: The higher breast cancer detection rate with DBT screening includes a relevant percentage of breast cancers that were only detected by one reader in an independent double reading. As in digital mammography, independent double reading continues to be justified in screening with digital breast tomosynthesis. KEY POINTS: · The percentages of discordant cancer reading results were 26.9 % and 22.2 % for DBT+SM and DM, respectively.. · The single true-positive detection rate was 2.3 ‰ for DBT+ SM and 1.4 ‰ for DM.. · A relevant proportion of screening-detected cancers resulted from a single true-positive reading.. CITATION FORMAT: · Weigel S, Hense HW, Weyer-Elberich V et al. Breast cancer screening with digital breast tomosynthesis: Is independent double reading still required?. Fortschr Röntgenstr 2024; DOI: 10.1055/a-2216-1109.

Digital Breast Tomosynthesis versus Digital Mammography for Detection of Early-Stage Cancers Stratified by Grade: A TOSYMA Subanalysis.

Background Breast cancer screening with digital breast tomosynthesis (DBT) plus synthesized mammography (SM) increases invasive tumor detection compared with digital mammography (DM). However, it is not known how the prognostic characteristics of the cancers detected with the two screening approaches differ. Purpose To compare invasive breast cancers detected with DBT plus SM (test arm) versus DM (control arm) screening with regard to tumor stage, histologic grade, patient age, and breast density. Materials and Methods This exploratory subanalysis of the Tomosynthesis plus Synthesized Mammography (TOSYMA) study, which is a multicenter randomized controlled trial embedded in the German mammography screening program, recruited women aged 50-70 years from July 2018 to December 2020. It compared invasive cancer detection rates (iCDRs), rate differences, and odds ratios (ORs) between the arms stratified by Union for International Cancer Control (UICC) stage (I vs II-IV), histologic grade (1 vs 2 or 3), age group (50-59 vs 60-70 years), and Breast Imaging Reporting and Data System categories of breast density (A or B vs C or D). Results In total, 49 462 (median age, 57 years [IQR, 53-62 years]) and 49 669 (median age, 57 years [IQR, 53-62 years]) participants were allocated to DBT plus SM and DM screening, respectively. The iCDR of stage I tumors with DBT plus SM was 51.6 per 10 000 women (255 of 49 462) and with DM it was 30.0 per 10 000 women (149 of 49 669). DBT plus SM depicted more stage I tumors with grade 2 or 3 (166 of 49 462, 33.7 per 10 000 women) than DM (106 of 49 669, 21.3 per 10 000 women; rate difference, +12.3 per 10 000 women [95% CI: 0.3, 24.9]; OR, 1.6 [95% CI: 0.9, 2.7]). DBT plus SM achieved the highest iCDR of stage I tumors with grade 2 or 3 among women aged 60-70 years with dense breasts (41 of 7364, 55.4 per 10 000 women; rate difference, +21.6 per 10 000 women [95% CI: -21.1, 64.3]; OR, 1.6 [95% CI: 0.6, 4.5]). Conclusion DBT plus SM screening appears to lead to higher detection of early-stage invasive breast cancers of grade 2 or 3 than DM screening, with the highest rate among women aged 60-70 years with dense breasts. Clinical trial registration no. NCT03377036 © RSNA, 2023 See also the editorial by Ha and Chang in this issue.

Preoperative breast MRI positively impacts surgical outcomes of needle biopsy-diagnosed pure DCIS: a patient-matched analysis from the MIPA study.

OBJECTIVES: To investigate the influence of preoperative breast MRI on mastectomy and reoperation rates in patients with pure ductal carcinoma in situ (DCIS). METHODS: The MIPA observational study database (7245 patients) was searched for patients aged 18-80 years with pure unilateral DCIS diagnosed at core needle or vacuum-assisted biopsy (CNB/VAB) and planned for primary surgery. Patients who underwent preoperative MRI (MRI group) were matched (1:1) to those who did not receive MRI (noMRI group) according to 8 confounding covariates that drive referral to MRI (age; hormonal status; familial risk; posterior-to-nipple diameter; BI-RADS category; lesion diameter; lesion presentation; surgical planning at conventional imaging). Surgical outcomes were compared between the matched groups with nonparametric statistics after calculating odds ratios (ORs). RESULTS: Of 1005 women with pure unilateral DCIS at CNB/VAB (507 MRI group, 498 noMRI group), 309 remained in each group after matching. First-line mastectomy rate in the MRI group was 20.1% (62/309 patients, OR 2.03) compared to 11.0% in the noMRI group (34/309 patients, p = 0.003). The reoperation rate was 10.0% in the MRI group (31/309, OR for reoperation 0.40) and 22.0% in the noMRI group (68/309, p < 0.001), with a 2.53 OR of avoiding reoperation in the MRI group. The overall mastectomy rate was 23.3% in the MRI group (72/309, OR 1.40) and 17.8% in the noMRI group (55/309, p = 0.111). CONCLUSIONS: Compared to those going directly to surgery, patients with pure DCIS at CNB/VAB who underwent preoperative MRI had a higher OR for first-line mastectomy but a substantially lower OR for reoperation. CLINICAL RELEVANCE STATEMENT: When confounding factors behind MRI referral are accounted for in the comparison of patients with CNB/VAB-diagnosed pure unilateral DCIS, preoperative MRI yields a reduction of reoperations that is more than twice as high as the increase in overall mastectomies. KEY POINTS: • Confounding factors cause imbalance when investigating the influence of preoperative MRI on surgical outcomes of pure DCIS. • When patient matching is applied to women with pure unilateral DCIS, reoperation rates are significantly reduced in women who underwent preoperative MRI. • The reduction of reoperations brought about by preoperative MRI is more than double the increase in overall mastectomies.

Screening and diagnostic breast MRI: how do they impact surgical treatment? Insights from the MIPA study.

OBJECTIVES: To report mastectomy and reoperation rates in women who had breast MRI for screening (S-MRI subgroup) or diagnostic (D-MRI subgroup) purposes, using multivariable analysis for investigating the role of MRI referral/nonreferral and other covariates in driving surgical outcomes. METHODS: The MIPA observational study enrolled women aged 18-80 years with newly diagnosed breast cancer destined to have surgery as the primary treatment, in 27 centres worldwide. Mastectomy and reoperation rates were compared using non-parametric tests and multivariable analysis. RESULTS: A total of 5828 patients entered analysis, 2763 (47.4%) did not undergo MRI (noMRI subgroup) and 3065 underwent MRI (52.6%); of the latter, 2441/3065 (79.7%) underwent MRI with preoperative intent (P-MRI subgroup), 510/3065 (16.6%) D-MRI, and 114/3065 S-MRI (3.7%). The reoperation rate was 10.5% for S-MRI, 8.2% for D-MRI, and 8.5% for P-MRI, while it was 11.7% for noMRI (p ≤ 0.023 for comparisons with D-MRI and P-MRI). The overall mastectomy rate (first-line mastectomy plus conversions from conserving surgery to mastectomy) was 39.5% for S-MRI, 36.2% for P-MRI, 24.1% for D-MRI, and 18.0% for noMRI. At multivariable analysis, using noMRI as reference, the odds ratios for overall mastectomy were 2.4 (p < 0.001) for S-MRI, 1.0 (p = 0.957) for D-MRI, and 1.9 (p < 0.001) for P-MRI. CONCLUSIONS: Patients from the D-MRI subgroup had the lowest overall mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). This analysis offers an insight into how the initial indication for MRI affects the subsequent surgical treatment of breast cancer. KEY POINTS: • Of 3065 breast MRI examinations, 79.7% were performed with preoperative intent (P-MRI), 16.6% were diagnostic (D-MRI), and 3.7% were screening (S-MRI) examinations. • The D-MRI subgroup had the lowest mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). • The S-MRI subgroup had the highest mastectomy rate (39.5%) which aligns with higher-than-average risk in this subgroup, with a reoperation rate (10.5%) not significantly different to that of all other subgroups.

Artificial Intelligence for Indication of Invasive Assessment of Calcifications in Mammography Screening. / Künstliche Intelligenz zur Indikationsstellung einer invasiven Mikrokalkabklärung im Mammografie-Screening.

PURPOSE: Lesion-related evaluation of the diagnostic performance of an individual artificial intelligence (AI) system to assess mamographically detected and histologically proven calcifications. MATERIALS AND METHODS: This retrospective study included 634 women of one screening unit (July 2012 - June 2018) who completed the invasive assessment of calcifications. For each leasion, the AI-system calculated a score between 0 and 98. Lesions scored > 0 were classified as AI-positive. The performance of the system was evaluated based on its positive predictive value of invasive assessment (PPV3), the false-negative rate and the true-negative rate. RESULTS: The PPV3 increased across the categories (readers: 4a: 21.2 %, 4b: 57.7 %, 5: 100 %, overall 30.3 %; AI: 4a: 20.8 %, 4b: 57.8 %, 5: 100 %, overall: 30.7 %). The AI system yielded a false-negative rate of 7.2 % (95 %-CI: 4.3 %: 11.4 %) and a true-negative rate of 9.1 % (95 %-CI: 6.6 %; 11.9 %). These rates were highest in category 4a, 12.5 % and 10.4 % retrospectively. The lowest median AI score was observed for benign lesions (61, interquartile range (IQR): 45-74). Invasive cancers yielded the highest median AI score (81, IQR: 64-86). Median AI scores for ductal carcinoma in situ were: 74 (IQR: 63-84) for low grade, 70 (IQR: 52-79) for intermediate grade and 74 (IQR: 66-83) for high grade. CONCLUSION: At the lowest threshold, the AI system yielded calcification-related PPV3 values that increased across categories, similar as seen in human evaluation. The strongest loss in AI-based breast cancer detection was observed for invasively assessed calcifications with the lowest suspicion of malignancy, yet with a comparable decrease in the false-positive rate. An AI-score based stratification of malignant lesions could not be determined. KEY POINTS: · The AI-based PPV3 for calcifications is comparable to human assessment.. · AI showed a lower detection performance of screen-positive and screen-negative lesions in category 4a.. · Histological subgroups could not be discriminated by AI scores.. CITATION FORMAT: · Weigel S, Brehl AK, Heindel W et al. Artificial Intelligence for Indication of Invasive Assessment of Calcifications in Mammography Screening. Fortschr Röntgenstr 2023; 195: 38 - 46.

Initial Results of 68Ga-FAPI-46 PET/MRI to Assess Response to Neoadjuvant Chemotherapy in Breast Cancer.

Improving imaging-based response after neoadjuvant chemotherapy (NAC) in breast cancer assessment could obviate histologic confirmation of pathologic complete response (pCR) and facilitate deescalation of chemotherapy or surgery. Fibroblast activation protein inhibitor (FAPI) PET/MRI is a promising novel molecular imaging agent for the tumor microenvironment with intense uptake in breast cancer. We assessed the diagnostic performance of follow-up breast 68Ga-FAPI-46 (68Ga-FAPI) PET/MRI in classifying the response status of local breast cancer and lymph node metastases after completion of NAC and validated this approach immunohistochemically. Methods: In women who completed NAC for invasive breast cancer, follow-up 68Ga-FAPI PET/MRI and corresponding fibroblast activation protein (FAP) immunostainings were retrospectively analyzed. Metrics of 68Ga-FAPI uptake and FAP immunoreactivity in women with or without pCR were compared using the Mann-Whitney U test. Diagnostic performance to detect remnant invasive cancer was calculated for tracer uptake metrics using receiver-operating-characteristic curves and for masked readers' visual assessment categories of PET/MRI and MRI alone. Results: Thirteen women (mean age ± SD, 47 ± 9 y) were evaluated. Seven of the 13 achieved pCR in the breast and 6 in the axilla. FAP immunoreactivity was significantly associated with response status. The 68Ga-FAPI PET/MRI mean breast tumor-to-background ratio was 0.9 (range, 0.6-1.2) for pCR and 2.1 (range, 1.4-3.1) for no pCR (P = 0.001). Integrated PET/MRI could classify breast response correctly in all 13 women based on readers' visual assessment or tumor-to-background ratio. Evaluation of MRI alone resulted in at least 2 false-positives. For lymph nodes, PET/MRI readers had at least 2 false-negative classifications, whereas MRI alone resulted in 2 false-negatives and 1 false-positive. Conclusion: To our knowledge, this was the first analysis of 68Ga-FAPI PET/MRI for response assessment after NAC for breast cancer. The diagnostic performance of PET/MRI in a small study sample trended toward a gain over MRI alone, clearly supporting future prospective studies.

Breast Density and Breast Cancer Screening with Digital Breast Tomosynthesis: A TOSYMA Trial Subanalysis.

Background Digital breast tomosynthesis (DBT) plus synthesized mammography (SM) reduces the diagnostic pitfalls of tissue superimposition, which is a limitation of digital mammography (DM). Purpose To compare the invasive breast cancer detection rate (iCDR) of DBT plus SM versus DM screening for different breast density categories. Materials and Methods An exploratory subanalysis of the TOmosynthesis plus SYnthesized MAmmography (TOSYMA) study, a randomized, controlled, multicenter, parallel-group trial recruited within the German mammography screening program from July 2018 to December 2020. Women aged 50-69 years were randomly assigned (1:1) to DBT plus SM or DM screening examination. Breast density categories A-D were visually assessed according to the Breast Imaging Reporting and Data System Atlas. Exploratory analyses were performed of the iCDR in both study arms and stratified by breast density, and odds ratios and 95% CIs were determined. Results A total of 49 762 women allocated to DBT plus SM and 49 796 allocated to DM (median age, 57 years [IQR, 53-62 years]) were included. In the DM arm, the iCDR was 3.6 per 1000 screening examinations in category A (almost entirely fatty) (16 of 4475 screenings), 4.3 in category B (102 of 23 534 screenings), 6.1 in category C (116 of 19 051 screenings), and 2.3 in category D (extremely dense breasts) (six of 2629 screenings). The iCDR in the DBT plus SM arm was 2.7 per 1000 screening examinations in category A (12 of 4439 screenings), 6.9 in category B (154 of 22 328 screenings), 8.3 in category C (156 of 18 772 screenings), and 8.1 in category D (32 of 3940 screenings). The odds ratio for DM versus DBT plus SM in category D was 3.8 (95% CI: 1.5, 11.1). The invasive cancers detected with DBT plus SM were most often grade 2 tumors; in category C, it was 58% (91 of 156 invasive cancers), and in category D, it was 47% (15 of 32 invasive cancers). Conclusion The TOmosynthesis plus SYnthesized MAmmography trial revealed higher invasive cancer detection rates with digital breast tomosynthesis plus synthesized mammography than digital mammography in dense breasts, relatively and absolutely most marked among women with extremely dense breasts. ClinicalTrials.gov registration no.: NCT03377036 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Lee and Moy in this issue.

Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial.

BACKGROUND: Two dimensional (2D) full-field digital mammography is the current standard of breast cancer screening. Digital breast tomosynthesis generates pseudo-three dimensional datasets of the breast from which synthesised 2D (s2D) mammograms can be reconstructed. This innovative approach reduces the likelihood of overlapping breast tissues that can conceal features of malignancy. We aimed to compare digital breast tomosynthesis plus s2D mammography with digital screening mammography for the detection of invasive breast cancer. METHODS: TOSYMA was a randomised, open-label, superiority trial done at 17 screening units in two federal states of Germany. Eligible participants were women aged 50-69 years who had been invited to participate in a population-wide, quality-controlled mammography screening programme. Women were randomly assigned (1:1) to digital breast tomosynthesis plus s2D mammography or digital mammography alone using block randomisation (block size of 32), stratified by site. The primary endpoints were the detection rate of invasive breast cancer and invasive interval cancer rate at 24 months, analysed in the modified full analysis set, which included all randomly assigned participants who underwent either type of screening examination. Ten examinations, corresponding to a second study participation, were excluded. Analyses were done according to the intention-to-treat principle. Interval cancer rates will be reported in the follow-up study. Safety was assessed in the as-treated population, which included all participants who were randomly assigned. This trial is registered with ClinicalTrials.gov, NCT03377036, and is closed to accrual. FINDINGS: Between July 5, 2018, and Dec 30, 2020, 99 689 women were randomly assigned to digital breast tomosynthesis plus s2D mammography (n=49 804) or digital mammography (n=49 830). Invasive breast cancers were detected in 354 of 49 715 women with evaluable primary endpoint data in the digital breast tomosynthesis plus s2D group (detection rate 7·1 cases per 1000 women screened) and in 240 of 49 762 women in the digital mammography group (4·8 cases per 1000 women screened; odds ratio 1·48 [95% CI 1·25-1·75]; p<0·0001). Adverse events and device deficiencies were rare (six adverse events in each group; 23 device deficiencies in the digital breast tomosynthesis plus s2D group vs five device deficiencies in the digital mammography group) and no serious adverse events were reported. INTERPRETATION: The results from this study indicate that the detection rate for invasive breast cancer was significantly higher with digital breast tomosynthesis plus s2D mammography than digital mammography alone. Evaluation of interval cancer rates in the follow-up study will further help to investigate incremental long-term benefits of digital breast tomosynthesis screening. FUNDING: Deutsche Forschungsgemeinschaft (German Research Foundation).

Using deep learning to assist readers during the arbitration process: a lesion-based retrospective evaluation of breast cancer screening performance.

OBJECTIVES: To evaluate if artificial intelligence (AI) can discriminate recalled benign from recalled malignant mammographic screening abnormalities to improve screening performance. METHODS: A total of 2257 full-field digital mammography screening examinations, obtained 2011-2013, of women aged 50-69 years which were recalled for further assessment of 295 malignant out of 305 truly malignant lesions and 2289 benign lesions after independent double-reading with arbitration, were included in this retrospective study. A deep learning AI system was used to obtain a score (0-95) for each recalled lesion, representing the likelihood of breast cancer. The sensitivity on the lesion level and the proportion of women without false-positive ratings (non-FPR) resulting under AI were estimated as a function of the classification cutoff and compared to that of human readers. RESULTS: Using a cutoff of 1, AI decreased the proportion of women with false-positives from 89.9 to 62.0%, non-FPR 11.1% vs. 38.0% (difference 26.9%, 95% confidence interval 25.1-28.8%; p < .001), preventing 30.1% of reader-induced false-positive recalls, while reducing sensitivity from 96.7 to 91.1% (5.6%, 3.1-8.0%) as compared to human reading. The positive predictive value of recall (PPV-1) increased from 12.8 to 16.5% (3.7%, 3.5-4.0%). In women with mass-related lesions (n = 900), the non-FPR was 14.2% for humans vs. 36.7% for AI (22.4%, 19.8-25.3%) at a sensitivity of 98.5% vs. 97.1% (1.5%, 0-3.5%). CONCLUSION: The application of AI during consensus conference might especially help readers to reduce false-positive recalls of masses at the expense of a small sensitivity reduction. Prospective studies are needed to further evaluate the screening benefit of AI in practice. KEY POINTS: • Integrating the use of artificial intelligence in the arbitration process reduces benign recalls and increases the positive predictive value of recall at the expense of some sensitivity loss. • Application of the artificial intelligence system to aid the decision to recall a woman seems particularly beneficial for masses, where the system reaches comparable sensitivity to that of the readers, but with considerably reduced false-positives. • About one-fourth of all recalled malignant lesions are not automatically marked by the system such that their evaluation (AI score) must be retrieved manually by the reader. A thorough reading of screening mammograms by readers to identify suspicious lesions therefore remains mandatory.

Simultaneous FAPI PET/MRI Targeting the Fibroblast-Activation Protein for Breast Cancer.

Background Integrated PET/MRI is a promising modality for breast assessment. The most frequently used tracer, fluorine 18 (18F) fluorodeoxyglucose (FDG), is applied for whole-body staging in advanced breast cancer but has limited accuracy in evaluating primary breast lesions. The fibroblast-activation protein (FAP) is abundantly expressed in invasive breast cancer. FAP-directed PET tracers have recently become available, but results in primary breast tumors remain lacking. Purpose To evaluate the use of FAP inhibitor (FAPI) breast PET/MRI in assessing breast lesions and of FAPI whole-body scanning for lymph node (LN) and distant staging using the ligand gallium 68 (68Ga)-FAPI-46. Materials and Methods In women with histologically confirmed invasive breast cancer, all primary 68Ga-FAPI-46 breast and whole-body PET/MRI and PET/CT examinations conducted at the authors' center between October 2019 and December 2020 were retrospectively analyzed. MRI lesion characteristics and standardized uptake values (SUVs) were quantified with dedicated software. Mann-Whitney U tests were used to compare tumor SUVs across different tumor types. The Pearson correlation coefficient was calculated between SUV and measures of MRI morphologic characteristics. Results Nineteen women (mean age, 49 years ± 9 [standard deviation]) were evaluated-18 to complement initial staging and one for restaging after therapy for distant metastases. Strong tracer accumulation was observed in all 18 untreated primary breast malignancies (mean maximum SUV [SUVmax] = 13.9 [range, 7.9-29.9]; median lesion diameter = 26 mm [range, 9-155 mm]), resulting in clear tumor delineation across different gradings, receptors, and histologic types. All preoperatively verified LN metastases in 13 women showed strong tracer accumulation (mean SUVmax= 12.2 [range, 3.3-22.4]; mean diameter = 21 mm [range, 14-35 mm]). Tracer uptake established or supported extra-axillary LN involvement in seven women and affected therapy decisions in three women. Conclusion This retrospective analysis indicates use of 68Ga fibroblast-activation protein inhibitor tracers for breast cancer diagnosis and staging. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mankoff and Sellmyer in this issue.

Magnetic resonance imaging before breast cancer surgery: results of an observational multicenter international prospective analysis (MIPA).

OBJECTIVES: Preoperative breast magnetic resonance imaging (MRI) can inform surgical planning but might cause overtreatment by increasing the mastectomy rate. The Multicenter International Prospective Analysis (MIPA) study investigated this controversial issue. METHODS: This observational study enrolled women aged 18-80 years with biopsy-proven breast cancer, who underwent MRI in addition to conventional imaging (mammography and/or breast ultrasonography) or conventional imaging alone before surgery as routine practice at 27 centers. Exclusion criteria included planned neoadjuvant therapy, pregnancy, personal history of any cancer, and distant metastases. RESULTS: Of 5896 analyzed patients, 2763 (46.9%) had conventional imaging only (noMRI group), and 3133 (53.1%) underwent MRI that was performed for diagnosis, screening, or unknown purposes in 692/3133 women (22.1%), with preoperative intent in 2441/3133 women (77.9%, MRI group). Patients in the MRI group were younger, had denser breasts, more cancers ≥ 20 mm, and a higher rate of invasive lobular histology than patients who underwent conventional imaging alone (p < 0.001 for all comparisons). Mastectomy was planned based on conventional imaging in 22.4% (MRI group) versus 14.4% (noMRI group) (p < 0.001). The additional planned mastectomy rate in the MRI group was 11.3%. The overall performed first- plus second-line mastectomy rate was 36.3% (MRI group) versus 18.0% (noMRI group) (p < 0.001). In women receiving conserving surgery, MRI group had a significantly lower reoperation rate (8.5% versus 11.7%, p < 0.001). CONCLUSIONS: Clinicians requested breast MRI for women with a higher a priori probability of receiving mastectomy. MRI was associated with 11.3% more mastectomies, and with 3.2% fewer reoperations in the breast conservation subgroup. KEY POINTS: • In 19% of patients of the MIPA study, breast MRI was performed for screening or diagnostic purposes. • The current patient selection to preoperative breast MRI implies an 11% increase in mastectomies, counterbalanced by a 3% reduction of the reoperation rate. • Data from the MIPA study can support discussion in tumor boards when preoperative MRI is under consideration and should be shared with patients to achieve informed decision-making.

[Systematic and quality-assured early diagnosis of sporadic breast cancer : Update on screening effects and scientific studies]. / Systematische und qualitätsgesicherte Früherkennung des sporadischen Mammakarzinoms : Update Screening-Effekte und wissenschaftliche Studien.

BACKGROUND: A quality-assured mammography screening programme has been available since 2009, nationwide, to all women in Germany between the ages of 50 and 69. The programme is based on the European Guidelines. In this review article the authors summarize the current status of scientific assessments of this national early detection programme for breast cancer and provide an outlook regarding ongoing studies on effectiveness tests and further development. RESULTS: We expect a decline in mortality rates relating to breast cancer as a result of successfully bringing diagnoses forward and a decrease in advanced breast cancer after a repeated screening. The extent will be shown in the current ZEBra study on mortality evaluation. CONCLUSION: Potential for a further increase in the effectiveness of the systematic early detection of breast cancer can be identified in four areas: (1) More women should take advantage of the early detection opportunities offered by the medical insurance funds; so far, on average, only about 50% of the women between 50 and 69 who are entitled to a screening examination actually take part in the programme. (2) Entitlement to take part in the programme should be extended to women over 70. (3) The further development of digital mammography towards digital breast tomosynthesis promises to reduce the number of false positive recalls while at the same time increasing sensitivity. (4) There should be scientific studies relating to an extension of screening strategies for the small number of women in the entitlement range who have extremly dense breasts.

Solving the preoperative breast MRI conundrum: design and protocol of the MIPA study.

Despite its high diagnostic performance, the use of breast MRI in the preoperative setting is controversial. It has the potential for personalized surgical management in breast cancer patients, but two of three randomized controlled trials did not show results in favor of its introduction for assessing the disease extent before surgery. Meta-analyses showed a higher mastectomy rate in women undergoing preoperative MRI compared to those who do not. Nevertheless, preoperative breast MRI is increasingly used and a survey from the American Society of Breast Surgeons showed that 41% of respondents ask for it in daily practice. In this context, a large-scale observational multicenter international prospective analysis (MIPA study) was proposed under the guidance of the European Network for the Assessment of Imaging in Medicine (EuroAIM). The aims were (1) to prospectively and systematically collect data on consecutive women with a newly diagnosed breast cancer, not candidates for neoadjuvant therapy, who are offered or not offered breast MRI before surgery according to local practice; (2) to compare these two groups in terms of surgical and clinical endpoints, adjusting for covariates. The underlying hypotheses are that MRI does not cause additional mastectomies compared to conventional imaging, while reducing the reoperation rate in all or in subgroups of patients. Ninety-six centers applied to a web-based call; 36 were initially selected based on volume and quality standards; 27 were active for enrollment. On November 2018, the target of 7000 enrolled patients was reached. The MIPA study is presently at the analytic phase. Key Points • Breast MRI has a high diagnostic performance but its utility in the preoperative setting is controversial. • A large-scale observational multicenter prospective study was launched to compare women receiving with those not receiving preoperative MRI. • Twenty-seven centers enrolled more than 7000 patients. The study is presently at the analytic phase.

Incidence of advanced-stage breast cancer in regular participants of a mammography screening program: a prospective register-based study.

BACKGROUND: The European Guidelines for breast cancer screening suggest that the impact of population-based mammography screening programmes (MSP) may be assessed using the relative reduction in the incidence of advanced breast cancer (ABC, that is, stage UICC II and higher) as a surrogate indicator of screening effectiveness. METHODS: This prospective, population register-based study contained individual data of 1,200,246 women (aged 50-69 years) who attended the initial prevalence screening between 2005 and 2009. Of them, 498,029 women returned for the regular (i.e., within 24 months) first subsequent, and 208,561 for the regular second subsequent incidence screenings. The incidence rate of ABC was calculated for the 24-months period following, but not including, the initial screening by incorporating all interval ABCs and all ABCs detected at the regular first incidence screening; the ABC rate for the second 24-months period was determined in the same way, including ABCs detected in the interval after the first and, respectively, at the second incidence screening. The relative reduction in the ABC incidence was derived by comparing the age-standardized rates in these two periods with an age-standardized reference incidence rate, observed in the target population before the MSP implementation. The strengths and weaknesses of this particular study design were contrasted with a recently published checklist of main methodological problems affecting studies of the effect of MSP on ABC incidence. RESULTS: The age-standardized ABC incidence rate was 291.6 per 100,000 women for the 24-months period subsequent to the initial screening, and 275.0/100,000 for the 24-months period following the first subsequent screening. Compared to the 2-year incidence of 349.4/100,000 before the start of the MSP, this amounted to a relative reduction of 16.5 and 21.3%, respectively, in the incidence of ABC among regular MSP participants. CONCLUSIONS: The design employed in this study avoids some of the substantial methodological limitations that compromised previous observational studies. Nevertheless, specific limitations prevail that demand a cautious interpretation of the results. Therefore, the study findings, indicating a reduction in ABC for regular MSP participants, need to be followed with respect to potential impacts on breast cancer mortality rates.

Stratification of Breast Cancer Risk in Terms of the Influence of Age and Mammographic density. / Stratifizierung des Brustkrebsrisikos hinsichtlich der Einflüsse von Alter und mammografischer Dichte.

PURPOSE: Analysis of the influence of the singular risk factors age and breast density on the 2-year incidence of breast cancer among participants in the German mammography screening program. MATERIALS AND METHODS: The multicenter study includes 111 456 subsequent round digital mammographic screening examinations from four screening units with prospective visual categorization of breast density. Based on detection in screening and during the 2-year interval after negative screening participation (interval cancers), 2-year breast cancer incidences (2 YBCI) (‰) were calculated in the 5-year age groups (5 YAG) of the target group 50-69 years and in the BI-RADS density categories ACR 1-4. Multivariate statistical evaluations were carried out using logistic regression models. RESULTS: With an increase in the 5 YAG, the 2 YBCI increased by 5.0 ‰, 6.7 ‰, 8.5 ‰ to 9.7 ‰, and was significantly different among 55-59, 60-64 and 65-69-year-old women compared to the youngest reference group 50-54 years (odds ratio (OR): 1.34; 1.68; and 1.93; p-value < 0.0001). With an increase in density categories 1-4, the 2 YBCI increased from 2.6 ‰, to 5.8 ‰, 9.6 ‰, and 9.7 ‰. The 2 YBCI differed significantly in breast density categories 2, 3, 4 from reference group 1 (OR: 2.17; 3.65; and 3.76; p-value < 0.0001). Only within the two main breast density groups 2 (frequency 44.3 %) and 3 (44.7 %), a significant increase in the 2 YBCI was observed across the 5 YAG (category 2: 3.7-8.9 ‰; category 3: 5.8-11.7 ‰; p-value < 0.001 each). The 2 YBCI was above the median of 7.5 ‰ in women with breast density category 2 and aged 65-69 years, as well as in women with breast density categories 3 and 4 aged 55-69 years. A 2 YBCI below the median was seen in women between 50-54 years regardless of breast density, as well as women in category 1 in all age groups. CONCLUSION: Within the main breast density categories 2 and 3 (almost 90 % of participants), incidences increase with age to double. A consistently low incidence is found regardless of breast density at a young screening age and in women with the lowest breast density. KEY POINTS: · The risk of breast cancer is modified by age in density categories.. · Women aged 50-54 years have a low risk in all density categories.. · Women in category ACR 1 of any age group have a low risk.. CITATION FORMAT: · Weigel S, Heindel W, Dietz C et al. Stratifizierung des Brustkrebsrisikos hinsichtlich der Einflüsse von Alter und mammografischer Dichte. Fortschr Röntgenstr 2020; 192: 678 - 685.

Breast cancer risk in BRCA1/2 mutation carriers and noncarriers under prospective intensified surveillance.

Comparably little is known about breast cancer (BC) risks in women from families tested negative for BRCA1/2 mutations despite an indicative family history, as opposed to BRCA1/2 mutation carriers. We determined the age-dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers of BRCA1/2 mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n = 4,380; 16,398 person-years [PY], median baseline age: 39 years) and CBC (n = 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8-70.9%) for BRCA1 mutation carriers, 43.2% (95% CI 32.1-56.3%) for BRCA2 mutation carriers and 15.7% (95% CI 11.9-20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9-29.8) for BRCA1 mutation carriers, 13.5 (95% CI 9.2-19.1) for BRCA2 mutation carriers and 4.9 (95% CI 3.8-6.3) for BRCA1/2 noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6-31.9%) for BRCA1 mutation carriers, 6.6% (95% CI 3.4-12.5%) for BRCA2 mutation carriers and 3.6% (95% CI 2.2-5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women from BRCA1/2 negative families with elevated risk.