Magnetic resonance imaging and ultrasound for prediction of residual tumor size in early breast cancer within the ADAPT subtrials.

BACKGROUND: Prediction of histological tumor size by post-neoadjuvant therapy (NAT) ultrasound and magnetic resonance imaging (MRI) was evaluated in different breast cancer subtypes. METHODS: Imaging was performed after 12-week NAT in patients enrolled into three neoadjuvant WSG ADAPT subtrials. Imaging performance was analyzed for prediction of residual tumor measuring ≤10 mm and summarized using positive (PPV) and negative (NPV) predictive values. RESULTS: A total of 248 and 588 patients had MRI and ultrasound, respectively. Tumor size was over- or underestimated by < 10 mm in 4.4% and 21.8% of patients by MRI and in 10.2% and 15.8% by ultrasound. Overall, NPV (proportion of correctly predicted tumor size ≤10 mm) of MRI and ultrasound was 0.92 and 0.83; PPV (correctly predicted tumor size > 10 mm) was 0.52 and 0.61. MRI demonstrated a higher NPV and lower PPV than ultrasound in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-positive and in HR-/HER2+ tumors. Both methods had a comparable NPV and PPV in HR-/HER2- tumors. CONCLUSIONS: In HR+/HER2+ and HR-/HER2+ breast cancer, MRI is less likely than ultrasound to underestimate while ultrasound is associated with a lower risk to overestimate tumor size. These findings may help to select the most optimal imaging approach for planning surgery after NAT. TRIAL REGISTRATION: Clinicaltrials.gov , NCT01815242 (registered on March 21, 2013), NCT01817452 (registered on March 25, 2013), and NCT01779206 (registered on January 30, 2013).

Early response by MR imaging and ultrasound as predictor of pathologic complete response to 12-week neoadjuvant therapy for different early breast cancer subtypes: Combined analysis from the WSG ADAPT subtrials.

We evaluated the role of early response after 3 weeks of neoadjuvant treatment (NAT) assessed by ultrasound (US), magnetic resonance imaging (MRI) and Ki-67 dynamics for prediction of pathologic complete response (pCR) in different early breast cancer subtypes. Patients with HR+/HER2+, HR-/HER2- and HR-/HER2+ tumors enrolled into three neoadjuvant WSG ADAPT subtrials underwent US, MRI and Ki-67 assessment at diagnosis and after 3 weeks of NAT. Early response was defined as complete or partial response (US, MRI) and ≥30% proliferation decrease or <500 invasive tumor cells (Ki-67). Predictive values and area under the receiver operating characteristic (AUC) curves for prediction of pCR (ypT0/is ypN0) after 12-week NAT were calculated. Two hundred twenty-six had MRI and 401 US; 107 underwent both MRI and US. All three methods yielded a similar AUC in HR+/HER2+ (0.66-0.67) and HR-/HER2- tumors (0.53-0.63), while MRI and Ki-67 performed better than US in HR-/HER2+ tumors (0.83 and 0.79 vs 0.56). Adding MRI+/-Ki-67 increased AUC of US in HR-/HER2+ tumors to 0.64 to 0.75. MRI and Ki-67 demonstrated highest sensitivity in HR-/HER2- (0.8-1) and HR-/HER2+ tumors (1, both). Negative predictive value was similar for all methods in HR+/HER2+ (0.71-0.74) and HR-/HER2- tumors (0.85-1), while it was higher for MRI and Ki-67 compared to US in HR-/HER2+ subtype (1 vs 0.5). Early response assessed by US, MRI and Ki-67 is a strong predictor for pCR after 12-week NAT. Strength of pCR prediction varies according to tumor subtype. Adding MRI+/-Ki-67 to US did not improve pCR prediction in majority of our patients.

Not all false positive diagnoses are equal: On the prognostic implications of false-positive diagnoses made in breast MRI versus in mammography / digital tomosynthesis screening.

BACKGROUND: Breast magnetic resonance imaging (MRI) has been reported to frequently result in false-positive diagnoses, limiting its positive predictive value (PPV). However, for PPV calculation, all nonmalignant tissue changes are equally considered false-positive, although the respective prognostic importance, and thus patient management implications, of different pathologies may well differ. We investigated the pathology of false-positive diagnoses made by MRI compared with radiographic (digital mammography/tomosynthesis [DM/DBT]) screening. METHODS: We conducted an institutional review board-approved prospective analysis of 710 consecutive asymptomatic women at average risk for breast cancer who underwent vacuum biopsy with or without surgical biopsy for screen-detected DM/DBT (n = 344) or MRI (n = 366) findings. We compared the frequency of false-positive biopsies (given by PPV3), as well as the types of nonmalignant tissue changes that caused the respective false-positive biopsies. In an order of increasing relative risk of subsequent breast cancer, pathologies of false-positive biopsies were categorized as nonproliferative, simple proliferative, complex proliferative, or atypical proliferative (including lobular carcinoma in situ/lobular intraepithelial neoplasia). The Mann-Whitney U test was used to compare distributions. RESULTS: Histology yielded nonmalignant tissue in 202 of 366 biopsies done for positive MRI studies and 195 of 344 biopsies for positive DM/DBT studies, respectively, yielding a similar PPV3 percentages of 44.8% (164 of 202) and 43.3% (149 of 202) for both methods. However, the distribution of tissue types that caused false-positive diagnoses differed significantly (p < 0.0001). On the basis of MRI, high-risk atypical proliferative changes (40.1%; 81 of 202) were most common, followed by complex proliferative changes (23.8%; 48 of 202). In DM/DBT, low-risk, nonproliferative changes were the dominant reason for false-positive diagnoses (49.7%; 97 of 195), followed by simple proliferative changes (25.2%; 51 of 195). Low-risk nonproliferative changes resulted in false-positive diagnoses based on MRI as infrequently as did high-risk atypical proliferative changes based on DM/DBT (18.8% [38 of 202] vs. 18.0% [35 of 195]). The likelihood of a false-positive diagnosis including atypias was twice as high in women undergoing biopsy for MRI findings (81 of 202; 40%) as for those with DM/DBT findings (35 of 195; 18%). CONCLUSIONS: The prognostic importance, and thus the clinical implications, of false-positive diagnoses made on the basis of breast MRI vs. radiographic screening differed significantly, with a reversed prevalence of high- and low-risk lesions. This should be taken into account when discussing the rate of false-positive diagnoses (i.e., PPV levels of MRI vs. radiographic screening). Current benchmarks that rate the utility of breast cancer screening programs (i.e., cancer detection rates and PPVs) do not reflect these substantial biological differences and the different prognostic implications.

Supplemental Breast MR Imaging Screening of Women with Average Risk of Breast Cancer.

Purpose To investigate the utility and accuracy of breast magnetic resonance (MR) imaging as a supplemental screening tool in women at average risk for breast cancer and to investigate the types of cancer detected with MR imaging screening. Materials and Methods This prospective observational study was conducted at two academic breast centers in women aged 40-70 years without breast cancer-associated risk factors (lifetime risk <15%). Between January 2005 and December 2013, women with at least minimal residual breast tissue (American College of Radiology categories A-D) and normal conventional imaging findings (screening mammography with or without screening ultrasonography [US]) were invited to undergo supplemental MR imaging screening. Outcome measures were supplemental cancer detection rates, interval cancer rates, and biologic profiles of MR imaging-detected additional cancers, as well as specificity and positive predictive value (PPV) of MR imaging screening. Tissue diagnoses or 2 years of follow-up were used to establish the reference standard. Results A total of 2120 women were recruited and underwent 3861 screening MR imaging studies, covering an observation period of 7007 women-years. Breast MR imaging depicted 60 additional breast cancers (ductal carcinoma in situ, n = 20; invasive carcinoma, n = 40) for an overall supplemental cancer detection rate of 15.5 per 1000 cases (95% confidence interval [CI]: 11.9, 20.0). Forty-eight additional cancers were detected with MR imaging at initial screening (supplemental cancer detection rate, 22.6 per 1000 cases). During the 1741 subsequent screening rounds, 12 of 13 incident cancers were found with MR imaging alone (supplemental cancer detection rate, 6.9 per 1000 cases). One cancer was diagnosed with all three methods (mammography, US, and MR imaging), and none were diagnosed with mammography only or US only. Cancers diagnosed with MR imaging were small (median, 8 mm), node negative in 93.4% of cases, and dedifferentiated (high-grade cancer) in 41.7% of cases at prevalence screening and 46.0% of cases at incidence screening. No interval cancers were observed. MR imaging screening offered high specificity (97.1%; 95% CI: 96.5, 97.6) and high PPV (35.7%; 95% CI: 28.9, 43.1). Conclusion In women at average risk for breast cancer, MR imaging screening improves early diagnosis of prognostically relevant breast cancer. © RSNA, 2017 Online supplemental material is available for this article.

Impact of Preoperative Breast MR Imaging and MR-guided Surgery on Diagnosis and Surgical Outcome of Women with Invasive Breast Cancer with and without DCIS Component.

Purpose To (a) compare the diagnostic accuracy of breast magnetic resonance (MR) imaging with that of conventional imaging (digital mammography and breast ultrasonography) in the identification of ductal carcinoma in situ (DCIS) components of biopsy-proven invasive breast cancer before surgery and (b) investigate the surgical outcome (positive margin rates and mastectomy rates) of women with breast cancer who underwent preoperative MR imaging combined with MR-guided needle biopsy and/or MR-guided lesion localization or bracketing where appropriate. Materials and Methods The authors performed a prospective two-center study of 593 consecutive patients with biopsy-proven invasive breast cancer who underwent breast MR imaging in addition to conventional imaging. MR-guided vacuum biopsy and MR-guided lesion bracketing were performed for DCIS components visible at MR imaging alone. The accuracy of breast MR imaging was compared with that of conventional imaging, and surgical outcomes (positive margin and mastectomy rates) were investigated. Results Surgical-pathologic assessment demonstrated DCIS components in 139 of the 593 women (23.4%). The sensitivity of MR imaging for the diagnosis of DCIS components pre-operatively (84.9%; 118 of 139) was significantly higher than that of conventional imaging (36.7%; 51 of 139) (P < .0001); more than half of DCIS components (51.1%; 71 of 139) were detected only with MR imaging. The sensitivity advantage of MR imaging over conventional imaging increased with increasing relative size of DCIS components, as follows: The sensitivity of MR imaging versus conventional imaging for small, marginal DCIS components was 56.8% (21 of 37) versus 29.7% (11 of 37); the sensitivity for extensive DCIS components was 91.7% (55 of 60) versus 41.7% (25 of 60); the sensitivity for large, predominant DCIS components was 100.0% (42 of 42) versus 35.7% (15 of 42). Moreover, the sensitivity advantage of MR imaging over conventional imaging increased with increasing nuclear grade of DCIS components, as follows: The sensitivity of MR imaging versus conventional imaging for low-grade DCIS components was 74.0% (20 of 27) versus 40.7% (11 of 27); the sensitivity for intermediate-grade DCIS components was 84.1% (53 of 63) versus 34.9% (22 of 63); the sensitivity for high-grade DCIS components was 91.8% (45 of 49) versus 36.7% (18 of 49) (P < .05-.001 for all). Positive margin rates were low overall (3.7% [95% Clopper Pearson confidence interval [CI]: 2.3%, 5.6%]) and did not differ significantly between the 139 women with DCIS components (5.0% [95% CI: 2.0%, 10.1%]) compared with the 454 women without such components (3.3% [95% CI: 1.9%, 5.4%]). The same was true for mastectomy rates (10.8% [95% CI: 6.2%, 17.2%] vs 8.1% [95% CI: 5.8%, 11.1%]). Conclusion Breast MR imaging improves depiction of DCIS components of invasive breast cancers before surgery and is associated with positive margin and mastectomy rates that are low irrespective of the presence or absence of DCIS components. © RSNA, 2017.

Assessment of BI-RADS category 4 lesions detected with screening mammography and screening US: utility of MR imaging.

PURPOSE: To investigate the utility of magnetic resonance (MR) imaging according to different types of Breast Imaging Reporting and Data System (BI-RADS) category 4 findings from screening mammography and/or screening ultrasonography (US). MATERIALS AND METHODS: This institutional review board-approved prospective study included 340 patients in whom 353 lesions were detected at screening mammography or US and were rated BI-RADS category 4 after appropriate conventional work-up. Written informed consent was obtained from all patients. Women underwent standard dynamic contrast material-enhanced MR imaging for further assessment. Women with negative or benign MR findings who did not proceed to biopsy underwent intensified follow-up for at least 18 months. Pure clustered microcalcifications were followed up for at least 24 months. RESULTS: Of the 353 study findings, 66 (18.7%) were finally shown to be true-positive (23 cases of ductal carcinoma in situ [DCIS], 43 invasive cancers) and 287 (81.3%) were false-positive. Assessment of MR imaging findings led to a correct diagnosis of no breast cancer in 264 of the 287 false-positive findings (92%) and helped confirm the presence of breast cancer in 63 of 66 malignancies. The false-negative rate for pure clustered microcalcifications was 12% (three of 25 cases) because of three nonenhancing low-grade DCIS cases; in turn, MR imaging depicted additional invasive cancers in three women with false-positive findings from mammography and US. For mammographic findings other than pure clustered microcalcifications, MR imaging increased the positive predictive value (PPV) from 17.5% (21 of 120 cases; 95% confidence interval [CI]: 10.7%, 24.3%) to 78% (21 of 27 cases; 95% CI: 62.1%, 93.5%), with a false-negative rate of 0%. For all US findings, MR imaging increased the PPV from 12.9% (20 of 155 cases; 95% CI: 7.6%, 18.2%) to 69% (20 of 29 cases; 95% CI: 52.2%, 85.8%), again with a false-negative rate of 0%. MR imaging resulted in false-positive findings that led to MR imaging-guided biopsy in five of the 340 patients (1.5%). CONCLUSION: MR imaging is useful for the noninvasive work-up of lesions classified as BI-RADS category 4 at mammography or US and can help avoid 92% of unnecessary biopsies. The false-negative rate was 0% for all US findings and for all mammographic findings except pure clustered microcalcifications. Additional invasive cancers were identified in three women with false-positive findings from mammography and US.

Digital breast tomosynthesis-guided vacuum-assisted breast biopsy: initial experiences and comparison with prone stereotactic vacuum-assisted biopsy.

PURPOSE: To use digital breast tomosynthesis (DBT)-guided vacuum-assisted biopsy (VAB) to sample target lesions identified at full-field digital screening mammography and compare clinical performance with that of prone stereotactic (PS) VAB. MATERIALS AND METHODS: In this institutional review board-approved study, 205 patients with 216 mammographic findings suspicious for cancer were scheduled to undergo mammography-guided VAB. Written informed consent was obtained. PS VAB was performed in 159 patients with 165 target lesions. DBT VAB was performed in 46 consecutive patients with 51 target lesions. Tissue-sampling methods and materials (9-gauge needles) were the same with both systems. For calcifications, specimen radiographs were obtained, and for masses or architectural distortions, control mammography or DBT was performed to confirm adequate target lesion sampling. χ(2) and Student t tests were used to compare biopsy time, and the Fisher exact test was used to compare lesion type distribution for DBT versus PS VAB. RESULTS: Technical success was achieved in 51 of 51 lesions (100%) with DBT VAB versus 154 of 165 lesions (93%) with PS VAB. In one of 11 lesions in which PS VAB failed, DBT VAB was performed successfully. Mean time to complete VAB was 13 minutes ± 3.7 for DBT VAB versus 29 minutes ± 10.1 for PS VAB (P < .0001). Reidentifying and targeting lesions during PS VAB took longer than it did during DBT VAB (P < .0001). Tissue sampling took about the same time for PS VAB and DBT VAB (P = .067). Significantly more "low-contrast" (ie, uncalcified) target lesions were biopsied with DBT VAB (13 of 51 lesions) versus PS VAB (nine of 165 lesions) (P < .0002). No major complications were observed with either system. One patient who underwent DBT VAB in the sitting position and one patient who underwent PS VAB developed self-limiting vasovagal reactions. CONCLUSION: Clinical performance of DBT VAB was significantly superior to PS VAB. Because DBT VAB allows use of the full detector size for imaging and provides immediate lesion depth information without requiring triangulation, it facilitates target lesion reidentification and sampling of even low-contrast targets, such as uncalcified masses.

Does MRI breast "density" (degree of background enhancement) correlate with mammographic breast density?

PURPOSE: To investigate whether mammographic breast densities and the respective degree of MRI background enhancement would correlate. Mammographic breast density is coded to communicate how likely a cancer is obscured by parenchyma. Similarly, background enhancement in breast MRI could obscure enhancing cancer tissue. MATERIALS AND METHODS: A total of 468 women underwent standard full-field digital mammography and dynamic contrast-enhanced breast MRI in our institution. Mammographic breast density was scored according to the American College of Radiology-classification; background enhancement in MRI was scored on a 4-point scale from absent to severe. Breast "density classes" were retrospectively compared by analyzing the differences between scores for mammography and MRI. Statistical correlation was calculated using the Spearman coefficient. RESULTS: Scores matched in 19% of women (90/468) but differed in 81% (378/468). A deviation by 1 point was observed in 33% (157/468), by 2 points in 38% (179/468), by 3 in 9% (42/468). Scores for background enhancement were lower than mammographic scores in 371/468 (79.3%), equivalent in 90/468 (19.2%), and higher in 7/468 (1.5%). CONCLUSION: Mammographic breast density does not correlate with the degree of background enhancement in MRI. In the majority of women, scores for background enhancement in MRI will be lower than the respective mammographic density scores.

Temperature-dependence of beam-driven dynamics in graphene-fullerene sandwiches.

C60 fullerenes encapsulated between graphene sheets were investigated by aberration-corrected high-resolution transmission electron microscopy at different temperatures, namely about 93 K, 293 K and 733 K, and by molecular dynamics simulations. We studied beam-induced dynamics of the C60 fullerenes and the encapsulating graphene, measured the critical doses for the initial damage to the fullerenes and followed the beam-induced polymerization. We find that, while the doses for the initial damage do not strongly depend on temperature, the clusters formed by the subsequent polymerization are more tubular at lower temperatures, while sheet-like structures are generated at higher temperatures. The experimental findings are supported by the results of first-principles and analytical potential molecular dynamics simulations. The merging of curved carbon sheets is clearly promoted at higher temperatures and proceeds at once over few-nm segments.

Accuracy of multi-parametric breast MR imaging for predicting pathological complete response of operable breast cancer prior to neoadjuvant systemic therapy.

OBJECTIVES: To evaluate whether multiparametric breast-MRI, obtained before the initiation of neoadjuvant systemic therapy (NST) for operable breast cancer, predicts which cancer will achieve a pathological complete response (pCR) after the completion of NST. METHODS: This was an IRB-approved retrospective study on 31 consecutive patients (median age, 56 years) with operable invasive breast cancer (median size: 22 mm; triple-negative: 11/31 [35%], HER2-positive: 7/31 [23%], triple-positive: 13/31 [42%]) who underwent multiparametric DCE-MRI before the initiation of NST. The MRI protocol consisted of high-resolution dynamic contrast-enhanced MRI (DCE-MRI), T2-TSE, and DWI (b-values 0, 100, 800 s/mm2). The results of surgical pathology after the completion of NST served as a standard of reference. Patient characteristics (age and menopausal status), pathological tumor characteristics (type, stage, nuclear grade, ER/PR and HER2 receptor status, and Ki-67 staining), and MRI characteristics (size, morphology, T2 signal intensity, enhancement kinetics, and ADC values) before NST were evaluated and compared between patients achieving pCR vs. non-pCR. RESULTS: Among 31 patients, 17 achieved pCR (55%) and 14 non-pCR (45%). No correlation was observed between patient- or tumor pathology-derived characteristics and pCR vs. non-pCR. Among MRI-derived tumor characteristics, tumor growth orientation parallel to Cooper's ligaments (p = 0.002) and wash-out rates (p = 0.019) correlated with pCR. Pre-NST ADC values were lower in patients achieving pCR (P = 0.086). CONCLUSIONS: A tumor growth pattern parallel with Cooper's ligaments and a fast wash-out rate on pre-treatment multiparametric MRI are predictive of pCR and more closely associated with pCR than ADC values.

Safety and Efficacy of Magnetic Resonance-Guided Vacuum-Assisted Large-Volume Breast Biopsy (MR-Guided VALB).

OBJECTIVE: Magnetic resonance (MR)-guided vacuum-biopsy is technically demanding and may fail depending on target-lesion size or breast size, and location of lesions within the breast. We developed an MR-guided vacuum-assisted biopsy protocol that collects larger amounts of tissue, aiming at an at least partial or complete ablation of the target-lesion, just as it is intended during surgical (excisional) biopsy. Rationale is to avoid biopsy failures (false-negative results due to undersampling) by collecting larger amounts of tissue. We report on our experience with MR-guided vacuum-assisted large-volume breast biopsy (VALB) (MR-guided VALB) with regard to clinical success and complication rates. MATERIALS: Institutional review board-approved analysis of 865 patients with 1414 MR imaging (MRI)-only breast lesions who underwent tissue sampling under MRI guidance. Magnetic resonance-guided VALB was performed on a 1.5 T-system with a 9G system. Per target lesion, we collected at least 24 samples, with the biopsy notch directed toward the position of the target until on postbiopsy control imaging the target lesion appeared completely or at least greatly removed. The standard-of-reference was established by at least 24-months follow-up (for benign biopsy results), or results of surgical histology (for malignant or borderline results). We investigated the technical success rates as a function of factors that usually interfere with MR-guided vacuum biopsy. RESULTS: Target lesions were located in the central versus peripheral parts of the breast in 66.6% (941/1414) versus 33.6% (473/1414), occurred in large, intermediate, or small breasts in 22.7% (321/1414), 56.4% (797/1414), or 20.9% (296/1414), corresponded to nonmass enhancement (NME) versus mass enhancement (ME) in 64.0% (905/1414) vs. 36.0% (509/1414), with an average size of 23 mm for NME versus 9 mm for ME, respectively. Primary technical failures, that is, inability to reach the target lesion occurred in 0.2% of patients (2/865) and 0.1% of target lesions (2/1414). Successful biopsy, that is, an MR-guided VALB diagnosis matching with the standard of reference, was achieved in 99.5% (859/863) of patients and 99.7% (1408/1412) target lesions that had been amenable to MR-guided VALB. In 0.5% of patients (4/863) and 0.3% of target lesions (4/1412), a radiologic-pathologic mismatch suggested a false-negative biopsy, confirmed by secondary excisional biopsy. The likelihood of failure was independent of the lesion's location in the breast, breast size, target lesion size, or target lesion type (NME vs ME). None of the patients with benign MR-guided VALB diagnoses developed breast cancer at the biopsy site during follow-up of 2 years. None of the patients developed major complications. CONCLUSION: Magnetic resonance-guided VALB is a safe procedure that is associated with a high success rate (99.7%) that is independent of the size, type, or location of a target lesion, or the size of the breast, and is associated with a very low complication rate.

Abbreviated breast magnetic resonance imaging (MRI): first postcontrast subtracted images and maximum-intensity projection-a novel approach to breast cancer screening with MRI.

PURPOSE: We investigated whether an abbreviated protocol (AP), consisting of only one pre- and one postcontrast acquisition and their derived images (first postcontrast subtracted [FAST] and maximum-intensity projection [MIP] images), was suitable for breast magnetic resonance imaging (MRI) screening. METHODS: We conducted a prospective observational reader study in 443 women at mildly to moderately increased risk who underwent 606 screening MRIs. Eligible women had normal or benign digital mammograms and, for those with heterogeneously dense or extremely dense breasts (n = 427), normal or benign ultrasounds. Expert radiologists reviewed the MIP image first to search for significant enhancement and then reviewed the complete AP (consisting of MIP and FAST images and optionally their nonsubtracted source images) to characterize enhancement and establish a diagnosis. Only thereafter was the regular full diagnostic protocol (FDP) analyzed. RESULTS: MRI acquisition time for FDP was 17 minutes, versus 3 minutes for the AP. Average time to read the single MIP and complete AP was 2.8 and 28 seconds, respectively. Eleven breast cancers (four ductal carcinomas in situ and seven invasive cancers; all T1N0 intermediate or high grade) were diagnosed, for an additional cancer yield of 18.2 per 1,000. MIP readings were positive in 10 (90.9%) of 11 cancers and allowed establishment of the absence of breast cancer, with a negative predictive value (NPV) of 99.8% (418 of 419). Interpretation of the complete AP, as with the FDP, allowed diagnosis of all cancers (11 [100%] of 11). Specificity and positive predictive value (PPV) of AP versus FDP were equivalent (94.3% v 93.9% and 24.4% v 23.4%, respectively). CONCLUSION: An MRI acquisition time of 3 minutes and an expert radiologist MIP image reading time of 3 seconds are sufficient to establish the absence of breast cancer, with an NPV of 99.8%. With a reading time < 30 seconds for the complete AP, diagnostic accuracy was equivalent to that of the FDP and resulted in an additional cancer yield of 18.2 per 1,000.