Minimally Invasive Breast Biopsy After Neoadjuvant Systemic Treatment to Identify Breast Cancer Patients with Residual Disease for Extended Neoadjuvant Treatment: A New Concept.

BACKGROUND: Breast cancer patients with residual disease after neoadjuvant systemic treatment (NAST) have a worse prognosis compared with those achieving a pathologic complete response (pCR). Earlier identification of these patients might allow timely, extended neoadjuvant treatment strategies. We explored the feasibility of a vacuum-assisted biopsy (VAB) after NAST to identify patients with residual disease (ypT+ or ypN+) prior to surgery. METHODS: We used data from a multicenter trial, collected at 21 study sites (NCT02948764). The trial included women with cT1-3, cN0/+ breast cancer undergoing routine post-neoadjuvant imaging (ultrasound, MRI, mammography) and VAB prior to surgery. We compared the findings of VAB and routine imaging with the histopathologic evaluation of the surgical specimen. RESULTS: Of 398 patients, 34 patients with missing ypN status and 127 patients with luminal tumors were excluded. Among the remaining 237 patients, tumor cells in the VAB indicated a surgical non-pCR in all patients (73/73, positive predictive value [PPV] 100%), whereas PPV of routine imaging after NAST was 56.0% (75/134). Sensitivity of the VAB was 72.3% (73/101), and 74.3% for sensitivity of imaging (75/101). CONCLUSION: Residual cancer found in a VAB specimen after NAST always corresponds to non-pCR. Residual cancer assumed on routine imaging after NAST corresponds to actual residual cancer in about half of patients. Response assessment by VAB is not safe for the exclusion of residual cancer. Response assessment by biopsies after NAST may allow studying the new concept of extended neoadjuvant treatment for patients with residual disease in future trials.

Can multi-modal radiomics using pretreatment ultrasound and tomosynthesis predict response to neoadjuvant systemic treatment in breast cancer?

OBJECTIVES: Response assessment to neoadjuvant systemic treatment (NAST) to guide individualized treatment in breast cancer is a clinical research priority. We aimed to develop an intelligent algorithm using multi-modal pretreatment ultrasound and tomosynthesis radiomics features in addition to clinical variables to predict pathologic complete response (pCR) prior to the initiation of therapy. METHODS: We used retrospective data on patients who underwent ultrasound and tomosynthesis before starting NAST. We developed a support vector machine algorithm using pretreatment ultrasound and tomosynthesis radiomics features in addition to patient and tumor variables to predict pCR status (ypT0 and ypN0). Findings were compared to the histopathologic evaluation of the surgical specimen. The main outcome measures were area under the curve (AUC) and false-negative rate (FNR). RESULTS: We included 720 patients, 504 in the development set and 216 in the validation set. Median age was 51.6 years and 33.6% (242 of 720) achieved pCR. The addition of radiomics features significantly improved the performance of the algorithm (AUC 0.72 to 0.81; p = 0.007). The FNR of the multi-modal radiomics and clinical algorithm was 6.7% (10 of 150 with missed residual cancer). Surface/volume ratio at tomosynthesis and peritumoral entropy characteristics at ultrasound were the most relevant radiomics. Hormonal receptors and HER-2 status were the most important clinical predictors. CONCLUSION: A multi-modal machine learning algorithm with pretreatment clinical, ultrasound, and tomosynthesis radiomics features may aid in predicting residual cancer after NAST. Pending prospective validation, this may facilitate individually tailored NAST regimens. CLINICAL RELEVANCE STATEMENT: Multi-modal radiomics using pretreatment ultrasound and tomosynthesis showed significant improvement in assessing response to NAST compared to an algorithm using clinical variables only. Further prospective validation of our findings seems warranted to enable individualized predictions of NAST outcomes. KEY POINTS: • We proposed a multi-modal machine learning algorithm with pretreatment clinical, ultrasound, and tomosynthesis radiomics features to predict response to neoadjuvant breast cancer treatment. • Compared with the clinical algorithm, the AUC of this integrative algorithm is significantly higher. • Used prior to the initiative of therapy, our algorithm can identify patients who will experience pathologic complete response following neoadjuvant therapy with a high negative predictive value.

Ultrasound Radiomics Features to Identify Patients With Triple-Negative Breast Cancer: A Retrospective, Single-Center Study.

OBJECTIVES: Patients with triple-negative breast cancer (TNBC) exhibit a fast tumor growth rate and poor survival outcomes. In this study, we aimed to develop and compare intelligent algorithms using ultrasound radiomics features in addition to clinical variables to identify patients with TNBC prior to histopathologic diagnosis. METHODS: We used single-center, retrospective data of patients who underwent ultrasound before histopathologic verification and subsequent neoadjuvant systemic treatment (NAST). We developed a logistic regression with an elastic net penalty algorithm using pretreatment ultrasound radiomics features in addition to patient and tumor variables to identify patients with TNBC. Findings were compared to the histopathologic evaluation of the biopsy specimen. The main outcome measure was the area under the curve (AUC). RESULTS: We included 1161 patients, 813 in the development set and 348 in the validation set. Median age was 50.1 years and 24.4% (283 of 1161) had TNBC. The integrative model using radiomics and clinical information showed significantly better performance in identifying TNBC compared to the radiomics model (AUC: 0.71, 95% confidence interval [CI]: 0.65-0.76 versus 0.64, 95% CI: 0.57-0.71, P = .004). The five most important variables were cN status, shape surface volume ratio (SA:V), gray level co-occurrence matrix (GLCM) correlation, gray level dependence matrix (GLDM) dependence nonuniformity normalized, and age. Patients with TNBC were more often categorized as BI-RADS 4 than BI-RADS 5 compared to non-TNBC patients (P = .002). CONCLUSION: A machine learning algorithm showed promising potential to identify patients with TNBC using ultrasound radiomics features and clinical information prior to histopathologic evaluation.

Intra- and Interobserver Reliability of Shear Wave Elastography in Breast Cancer Diagnosis.

OBJECTIVES: Shear wave elastography (SWE) is increasingly used in breast cancer diagnostics. However, large, prospective, multicenter data evaluating the reliability of SWE is missing. We evaluated the intra- and interobserver reliability of SWE in patients with breast lesions categorized as BIRADS 3 or 4. METHODS: We used data of 1288 women at 12 institutions in 7 countries with breast lesions categorized as BIRADS 3 to 4 who underwent conventional B-mode ultrasound and SWE. 1243 (96.5%) women had three repetitive conventional B-mode ultrasounds as well as SWE measurements performed by a board-certified senior physician. 375 of 1288 (29.1%) women received an additional ultrasound examination with B-mode and SWE by a second physician. Intraclass correlation coefficients (ICC) were calculated to examine intra- and interobserver reliability. RESULTS: ICC for intraobserver reliability showed an excellent correlation with ICC >0.9, while interobserver reliability was moderate with ICC of 0.7. There were no clinically significant differences in intraobserver reliability when SWE was performed in lesions categorized as BI-RADS 3 or 4 as well as in histopathologically benign or malignant lesions. CONCLUSION: Reliability of additional SWE was evaluated on a study cohort consisting of 1288 breast lesions categorized as BI-RADS 3 and 4. SWE shows an excellent intraobserver reliability and a moderate interobserver reliability in the evaluation of solid breast masses.

Conventional specimen radiography in breast-conserving therapy: a useful tool for intraoperative margin assessment after neoadjuvant therapy?

PURPOSE: A previous study in our breast unit showed that the diagnostic accuracy of intraoperative specimen radiography and its potential to reduce second surgeries in a cohort of patients treated with neoadjuvant chemotherapy were low, which questions the routine use of Conventional specimen radiography (CSR) in this patient group. This is a follow-up study in a larger cohort to further evaluate these findings. METHODS: This retrospective study included 376 cases receiving breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) of primary breast cancer. CSR was performed to assess potential margin infiltration and recommend an intraoperative re-excision of any radiologically positive margin. The histological workup of the specimen served as gold standard for the evaluation of the accuracy of CSR and the potential reduction of second surgeries by CSR-guided re-excisions. RESULTS: 362 patients with 2172 margins were assessed. The prevalence of positive margins was 102/2172 (4.7%). CSR had a sensitivity of 37.3%, a specificity of 85.6%, a positive predictive value (PPV) of 11.3%, and a negative predictive value (NPV) of 96.5%. The rate of secondary procedures was reduced from 75 to 37 with a number needed to treat (NNT) of CSR-guided intraoperative re-excisions of 10. In the subgroup of patients with clinical complete response (cCR), the prevalence of positive margins was 38/1002 (3.8%), PPV was 6.5% and the NNT was 34. CONCLUSION: This study confirms our previous finding that the rate of secondary surgeries cannot be significantly reduced by CSR-guided intraoperative re-excisions in cases with cCR after NACT. The routine use CSR after NACT is questionable, and alternative tools of intraoperative margin assessment should be evaluated.

Potential of Lesion-to-Fat Elasticity Ratio Measured by Shear Wave Elastography to Reduce Benign Biopsies in BI-RADS 4 Breast Lesions.

OBJECTIVES: We evaluated whether lesion-to-fat ratio measured by shear wave elastography in patients with Breast Imaging Reporting and Data System (BI-RADS) 3 or 4 lesions has the potential to further refine the assessment of B-mode ultrasound alone in breast cancer diagnostics. METHODS: This was a secondary analysis of an international diagnostic multicenter trial (NCT02638935). Data from 1288 women with breast lesions categorized as BI-RADS 3 and 4a-c by conventional B-mode ultrasound were analyzed, whereby the focus was placed on differentiating lesions categorized as BI-RADS 3 and BI-RADS 4a. All women underwent shear wave elastography and histopathologic evaluation functioning as reference standard. Reduction of benign biopsies as well as the number of missed malignancies after reclassification using lesion-to-fat ratio measured by shear wave elastography were evaluated. RESULTS: Breast cancer was diagnosed in 368 (28.6%) of 1288 lesions. The assessment with conventional B-mode ultrasound resulted in 53.8% (495 of 1288) pathologically benign lesions categorized as BI-RADS 4 and therefore false positives as well as in 1.39% (6 of 431) undetected malignancies categorized as BI-RADS 3. Additional lesion-to-fat ratio in BI-RADS 4a lesions with a cutoff value of 1.85 resulted in 30.11% biopsies of benign lesions which correspond to a reduction of 44.04% of false positives. CONCLUSIONS: Adding lesion-to-fat ratio measured by shear wave elastography to conventional B-mode ultrasound in BI-RADS 4a breast lesions could help reduce the number of benign biopsies by 44.04%. At the same time, however, 1.98% of malignancies were missed, which would still be in line with American College of Radiology BI-RADS 3 definition of <2% of undetected malignancies.

Impact of age on indication for chemotherapy in early breast cancer patients: results from 104 German institutions from 2008 to 2017.

PURPOSE: Today, the decision to treat patients with chemotherapy for early breast cancer (EBC) is made based on the patient's individual risk stratification and tumor biology. In cases with chemotherapy indication, the neoadjuvant application (NACT) is the preferred option in comparison with primary surgery and adjuvant chemotherapy (ACT). Age remains a relevant factor in the decision-making process. The aim of the present study was to illustrate the impact of age on the use of systemic therapy in clinical routine. METHODS: The study separately analyzed chemotherapy use among six age cohorts of EBC patients who had been treated at 104 German breast units between January 2008 and December 2017. RESULTS: In total, 124,084 patients were included, 46,279 (37.3%) of whom had received chemotherapy. For 44,765 of these cases, detailed information on treatment was available. Within this cohort, chemotherapy was administered as NACT to 14,783 patients (33.0%) and as ACT to 29,982 (67.0%) patients. Due to the higher prevalence of unfavorable tumor subtypes, younger patients had a higher rate of chemotherapy (≤ 29y: 74.2%; 30-39y: 71.3%) and a higher proportion of NACT administration ( ≤ 29y: 66.9%; 30-39y: 56.0%) in comparison with elderly patients, who had lower rates for overall chemotherapy (60-69y: 37.5%; ≥ 70y: 17.6%) and NACT (60-69y: 25.5%; ≥ 70y: 22.8%). Pathologic complete response was higher in younger than in older patients (≤ 29y: 30.4% vs. ≥ 70y: 16.7%), especially for HER2- subtypes. CONCLUSION: The data from the nationwide German cohort reveal relevant age-dependent discrepancies concerning the use of chemotherapy for EBC.

Predictive value of neutrophil-to-lymphocyte-ratio in neoadjuvant-treated patients with breast cancer.

PURPOSE: Breast cancer (BC) is the most common malignancy among women and prognosis is strongly influenced by tumor subtype. Neoadjuvant chemotherapy (NAC) is the standard treatment for both locally advanced- and early-stage triple-negative and Her2-positive BC. Pathologic complete response (pCR) to NAC is an important predictor of patient outcomes. Neutrophil-to-lymphocyte-ratio (NLR) in peripheral blood is associated with prognosis in various malignancies. Here, we investigated the value of the pretreatment NLR as a response predictor in neoadjuvant-treated patients with BC. METHODS: A retrospective chart analysis of 862 patients with invasive BC treated with NAC at the Heidelberg University Hospital during 2003-2015 was conducted. NLR was calculated as the ratio of the absolute neutrophil and lymphocyte counts in peripheral blood, and pCR was defined as absence of invasive or in situ carcinoma in breast and axillary lymph nodes. RESULTS: A total of 151 patients with invasive BC who underwent NAC were included in this study. NLR tended to be higher in the pCR group than the non-pCR group (p < 0.1). Analyses of BC subtypes demonstrated that NLR was significantly higher in the pCR- compared with the non-pCR group (3.304 vs. 2.379, respectively; p = 0.048) in patients with luminal B/Her2-negative tumors. Further, we found a significant difference in NLR according to remission status in postmenopausal patients (2.861 vs. 2.313, respectively; p = 0.043). CONCLUSION: NLR was significantly higher only for patients achieving pCR in the Luminal B/Her2-negative and postmenopausal subgroups. Hence, NLR is a candidate additional predictive factor in patients with Luminal B/Her2-negative BC.

The Potential of Shear Wave Elastography to Reduce Unnecessary Biopsies in Breast Cancer Diagnosis: An International, Diagnostic, Multicenter Trial.

PURPOSE: In this prospective, multicenter trial we evaluated whether additional shear wave elastography (SWE) for patients with BI-RADS 3 or 4 lesions on breast ultrasound could further refine the assessment with B-mode breast ultrasound for breast cancer diagnosis. MATERIALS AND METHODS: We analyzed prospective, multicenter, international data from 1288 women with breast lesions rated by conventional 2 D B-mode ultrasound as BI-RADS 3 to 4c and undergoing 2D-SWE. After reclassification with SWE the proportion of undetected malignancies should be < 2 %. All patients underwent histopathologic evaluation (reference standard). RESULTS: Histopathologic evaluation showed malignancy in 368 of 1288 lesions (28.6 %). The assessment with B-mode breast ultrasound resulted in 1.39 % (6 of 431) undetected malignancies (malignant lesions in BI-RADS 3) and 53.80 % (495 of 920) unnecessary biopsies (biopsies in benign lesions). Re-classifying BI-RADS 4a patients with a SWE cutoff of 2.55 m/s resulted in 1.98 % (11 of 556) undetected malignancies and a reduction of 24.24 % (375 vs. 495) of unnecessary biopsies. CONCLUSION: A SWE value below 2.55 m/s for BI-RADS 4a lesions could be used to downstage these lesions to follow-up, and therefore reduce the number of unnecessary biopsies by 24.24 %. However, this would come at the expense of some additionally missed cancers compared to B-mode breast ultrasound (rate of undetected malignancies 1.98 %, 11 of 556, versus 1.39 %, 6 of 431) which would, however, still be in line with the ACR BI-RADS 3 definition (< 2 % of undetected malignancies).

Best Practice Guideline - DEGUM Recommendations on Breast Ultrasound. / Best Practice Guideline ­ Empfehlungen der DEGUM zur Durchführung und Beurteilung der Mammasonografie.

Alongside mammography, breast ultrasound is an important and well-established method in assessment of breast lesions. With the "Best Practice Guideline", the DEGUM Breast Ultrasound (in German, "Mammasonografie") working group, intends to describe the additional and optional application modalities for the diagnostic confirmation of breast findings and to express DEGUM recommendations in this Part II, in addition to the current dignity criteria and assessment categories published in Part I, in order to facilitate the differential diagnosis of ambiguous lesions.The present "Best Practice Guideline" has set itself the goal of meeting the requirements for quality assurance and ensuring quality-controlled performance of breast ultrasound. The most important aspects of quality assurance are explained in this Part II of the Best Practice Guideline.

Diagnosing Pathologic Complete Response in the Breast After Neoadjuvant Systemic Treatment of Breast Cancer Patients by Minimal Invasive Biopsy: Oral Presentation at the San Antonio Breast Cancer Symposium on Friday, December 13, 2019, Program Number GS5-03.

OBJECTIVE: We evaluated the ability of minimally invasive, image-guided vacuum-assisted biopsy (VAB) to reliably diagnose a pathologic complete response in the breast (pCR-B). SUMMARY BACKGROUND DATA: Neoadjuvant systemic treatment (NST) elicits a pathologic complete response in up to 80% of women with breast cancer. In such cases, breast surgery, the gold standard for confirming pCR-B, may be considered overtreatment. METHODS: This multicenter, prospective trial enrolled 452 women presenting with initial stage 1-3 breast cancer of all biological subtypes. Fifty-four women dropped out; 398 were included in the full analysis. All participants had an imaging-confirmed partial or complete response to NST and underwent study-specific image-guided VAB before guideline-adherent breast surgery. The primary endpoint was the false-negative rate (FNR) of VAB-confirmed pCR-B. RESULTS: Image-guided VAB alone did not detect surgically confirmed residual tumor in 37 of 208 women [FNR, 17.8%; 95% confidence interval (CI), 12.8-23.7%]. Of these 37 women, 12 (32.4%) had residual DCIS only, 20 (54.1%) had minimal residual tumor (<5 mm), and 19 of 25 (76.0%) exhibited invasive cancer cellularity of ≤10%. In 19 of the 37 cases (51.4%), the false-negative result was potentially avoidable. Exploratory analysis showed that performing VAB with the largest needle by volume (7-gauge) resulted in no false-negative results and that combining imaging and image-guided VAB into a single diagnostic test lowered the FNR to 6.2% (95% CI, 3.4%-10.5%). CONCLUSIONS: Image-guided VAB missed residual disease more often than expected. Refinements in procedure and patient selection seem possible and necessary before omitting breast surgery.

Does conventional specimen radiography after neoadjuvant chemotherapy of breast cancer help to reduce the rate of second surgeries?

PURPOSE: This is the first study to systematically evaluate the diagnostic accuracy of intraoperative specimen radiography on margin level and its potential to reduce second surgeries in patients treated with neoadjuvant chemotherapy. METHODS: This retrospective study included 174 cases receiving breast conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) of primary breast cancer. Conventional specimen radiography (CSR) was performed to assess potential margin infiltration and recommend an intraoperative re-excision of any radiologically positive margin. The histological workup of the specimen served as gold standard for the evaluation of the accuracy of CSR and the potential reduction of second surgeries by CSR-guided re-excisions. RESULTS: 1044 margins were assessed. Of 47 (4.5%) histopathological positive margins, CSR identified 9 correctly (true positive). 38 infiltrated margins were missed (false negative). This resulted in a sensitivity of 19.2%, a specificity of 89.2%, a positive predictive value (PPV) of 7.7%, and a negative predictive value (NPV) of 95.9%. The rate of secondary procedures was reduced from 23 to 16 with a number needed to treat (NNT) of CSR-guided intraoperative re-excisions of 25. In the subgroup of patients with cCR, the prevalence of positive margins was 10/510 (2.0%), PPV was 1.9%, and the NNT was 85. CONCLUSION: Positive margins after NACT are rare and CSR has only a low sensitivity to detect them. Thus, the rate of secondary surgeries cannot be significantly reduced by recommending targeted re-excisions, especially in cases with cCR. In summary, CSR after NACT is inadequate for intraoperative margin assessment but remains useful to document removal of the biopsy site clip.

Vacuum-Assisted Breast Biopsy After Neoadjuvant Systemic Treatment for Reliable Exclusion of Residual Cancer in Breast Cancer Patients.

BACKGROUND: About 40 % of women with breast cancer achieve a pathologic complete response in the breast after neoadjuvant systemic treatment (NST). To identify these women, vacuum-assisted biopsy (VAB) was evaluated to facilitate risk-adaptive surgery. In confirmatory trials, the rates of missed residual cancer [false-negative rates (FNRs)] were unacceptably high (> 10%). This analysis aimed to improve the ability of VAB to exclude residual cancer in the breast reliably by identifying key characteristics of false-negative cases. METHODS: Uni- and multivariable logistic regressions were performed using data of a prospective multicenter trial (n = 398) to identify patient and VAB characteristics associated with false-negative cases (no residual cancer in the VAB but in the surgical specimen). Based on these findings FNR was exploratively re-calculated. RESULTS: In the multivariable analysis, a false-negative VAB result was significantly associated with accompanying ductal carcinoma in situ (DCIS) in the initial diagnostic biopsy [odds ratio (OR), 3.94; p < 0.001], multicentric disease on imaging before NST (OR, 2.74; p = 0.066), and age (OR, 1.03; p = 0.034). Exclusion of women with DCIS or multicentric disease (n = 114) and classication of VABs that did not remove the clip marker as uncertain representative VABs decreased the FNR to 2.9% (3/104). CONCLUSION: For patients without accompanying DCIS or multicentric disease, performing a distinct representative VAB (i.e., removing a well-placed clip marker) after NST suggests that VAB might reliably exclude residual cancer in the breast without surgery. This evidence will inform the design of future trials evaluating risk-adaptive surgery for exceptional responders to NST.

The importance of multi-modal imaging and clinical information for humans and AI-based algorithms to classify breast masses (INSPiRED 003): an international, multicenter analysis.

OBJECTIVES: AI-based algorithms for medical image analysis showed comparable performance to human image readers. However, in practice, diagnoses are made using multiple imaging modalities alongside other data sources. We determined the importance of this multi-modal information and compared the diagnostic performance of routine breast cancer diagnosis to breast ultrasound interpretations by humans or AI-based algorithms. METHODS: Patients were recruited as part of a multicenter trial (NCT02638935). The trial enrolled 1288 women undergoing routine breast cancer diagnosis (multi-modal imaging, demographic, and clinical information). Three physicians specialized in ultrasound diagnosis performed a second read of all ultrasound images. We used data from 11 of 12 study sites to develop two machine learning (ML) algorithms using unimodal information (ultrasound features generated by the ultrasound experts) to classify breast masses which were validated on the remaining study site. The same ML algorithms were subsequently developed and validated on multi-modal information (clinical and demographic information plus ultrasound features). We assessed performance using area under the curve (AUC). RESULTS: Of 1288 breast masses, 368 (28.6%) were histopathologically malignant. In the external validation set (n = 373), the performance of the two unimodal ultrasound ML algorithms (AUC 0.83 and 0.82) was commensurate with performance of the human ultrasound experts (AUC 0.82 to 0.84; p for all comparisons > 0.05). The multi-modal ultrasound ML algorithms performed significantly better (AUC 0.90 and 0.89) but were statistically inferior to routine breast cancer diagnosis (AUC 0.95, p for all comparisons ≤ 0.05). CONCLUSIONS: The performance of humans and AI-based algorithms improves with multi-modal information. KEY POINTS: • The performance of humans and AI-based algorithms improves with multi-modal information. • Multimodal AI-based algorithms do not necessarily outperform expert humans. • Unimodal AI-based algorithms do not represent optimal performance to classify breast masses.

A New Practical Decision Rule to Better Differentiate BI-RADS 3 or 4 Breast Masses on Breast Ultrasound.

OBJECTIVES: The BI-RADS classification provides a standardized way to describe ultrasound findings in breast cancer diagnostics. However, there is little information regarding which BI-RADS descriptors are most strongly associated with malignancy, to better distinguish BI-RADS 3 (follow-up imaging) and 4 (diagnostic biopsy) breast masses. METHODS: Patients were recruited as part of an international, multicenter trial (NCT02638935). The trial enrolled 1294 women (6 excluded) categorized as BI-RADS 3 or 4 upon routine B-mode ultrasound examination. Ultrasound images were evaluated by three expert physicians according to BI-RADS. All patients underwent histopathological confirmation (reference standard). We performed univariate and multivariate analyses (chi-square test, logistic regression, and Krippendorff's alpha). RESULTS: Histopathologic evaluation showed malignancy in 368 of 1288 masses (28.6%). Upon performing multivariate analysis, the following descriptors were significantly associated with malignancy (P < .05): age ≥50 years (OR 8.99), non-circumscribed indistinct (OR 4.05) and microlobulated margin (OR 2.95), nonparallel orientation (OR 2.69), and calcification (OR 2.64). A clinical decision rule informed by these results demonstrated a 97% sensitivity and missed fewer cancers compared to three physician experts (range of sensitivity 79-95%) and a previous decision rule (sensitivity 59%). Specificity was 44% versus 22-83%, respectively. The inter-reader reliability of the BI-RADS descriptors and of the final BI-RADS score was fair-moderate. CONCLUSIONS: A patient should undergo a diagnostic biopsy (BI-RADS 4) instead of follow-up imaging (BI-RADS 3) if the patient is 50 years or older or exhibits at least one of the following features: calcification, nonparallel orientation of mass, non-circumscribed margin, or posterior shadowing.

How previous treatment changes the metabolomic profile in patients with metastatic breast cancer.

PURPOSE: Metabolites are in the spotlight of attention as promising novel breast cancer biomarkers. However, no study has been conducted concerning changes in the metabolomics profile of metastatic breast cancer patients according to previous therapy. METHODS: We performed a retrospective, single-center, nonrandomized, partially blinded, treatment-based study. Metastatic breast cancer (MBC) patients were enrolled between 03/2010 and 09/2016 at the beginning of a new systemic therapy. The endogenous metabolites in the plasma samples were analyzed using the AbsoluteIDQ® p180 Kit (Biocrates Life Sciences AG, Innsbruck) a targeted, quality and quantitative-controlled metabolomics approach. The statistical analysis was performed using R package, version 3.3.1. ANOVA was used to statistically assess age differences within groups. Furthermore, we analyzed the CTC status of the patients using the CellSearch™ assay. RESULTS: We included 178 patients in our study. Upon dividing the study population according to therapy before study inclusion, we found the following: 4 patients had received no therapy, 165 chemotherapy, and 135 anti-hormonal therapy, 30 with anti-Her2 therapy and 38 had received treatment with bevacizumab. Two metabolites were found to be significantly different, depending on the further therapy of the patients: methionine and serine. Whereas methionine levels were higher in the blood of patients who received an anti-Her2-therapy, serine was lower in patients with endocrine therapy only. CONCLUSION: We identified two metabolites for which concentrations differed significantly depending on previous therapies, which could help to choose the next therapy in patients who have already received numerous different treatments.

Best Practice Guideline - DEGUM Recommendations on Breast Ultrasound. / Best Practice Guideline ­ Empfehlungen der DEGUM zur Durchführung und Beurteilung der Mammasonografie ­ TEIL I ­ Untersuchungstechnik, Ultraschall-DEGUM-Kriterien und deren Dokumentation.

For many years, breast ultrasound has been used in addition to mammography as an important method for clarifying breast findings. However, differences in the interpretation of findings continue to be problematic 1 2. These differences decrease the diagnostic accuracy of ultrasound after detection of a finding and complicate interdisciplinary communication and the comparison of scientific studies 3. In 1999, the American College of Radiology (ACR) created a working group (International Expert Working Group) that developed a classification system for ultrasound examinations based on the established BI-RADS classification of mammographic findings under consideration of literature data 4. Due to differences in content, the German Society for Ultrasound in Medicine (DEGUM) published its own BI-RADS-analogue criteria catalog in 2006 3. In addition to the persistence of differences in content, there is also an issue with formal licensing with the current 5th edition of the ACR BI-RADS catalog, even though the content is recognized by the DEGUM as another system for describing and documenting findings. The goal of the Best Practice Guideline of the Breast Ultrasound Working Group of the DEGUM is to provide colleagues specialized in senology with a current catalog of ultrasound criteria and assessment categories as well as best practice recommendations for the various ultrasound modalities.

Long-Term Patient Satisfaction and Quality of Life After Breast-Conserving Therapy: A Prospective Study Using the BREAST-Q.

BACKGROUND: Poor patient-reported satisfaction after breast-conserving therapy (BCT) has been associated with impaired health-related quality of life (HRQOL) and subsequent depression in retrospective analysis. This prospective cohort study aimed to assess the HRQOL of patients who have undergone BCT using the BREAST-Q, and to identify clinical risk factors for lower patient satisfaction. METHODS: Patients with primary breast cancer undergoing BCT were asked to complete the BREAST-Q preoperatively (T1) for baseline evaluation, then 3 to 4 weeks postoperatively (T2), and finally 1 year after surgery (T3). Clinicopathologic data were extracted from the patients' charts. Repeated measures analysis of variance (ANOVA) was used to determine significant differences in mean satisfaction and well-being levels among the test intervals. Multiple linear regression was used to evaluate risk factors for lower satisfaction. RESULTS: The study enrolled 250 patients. The lowest baseline BREAST-Q score was reported for "satisfaction with breast" (mean, 61 ± 19), but this increased postoperatively (mean, 66 ± 18) and was maintained at the 1 year follow-up evaluation (mean, 67 ± 21). "Physical well-being" decreased from T1 (mean, 82 ± 17) to T2 (mean, 28 ± 13) and did not recover much by T3 (mean, 33 ± 13), being the lowest BREAST-Q score postoperatively and in the 1-year follow-up evaluation. In multiple regression, baseline psychosocial well-being, body mass index (BMI), and type of incision were risk factors for lower "satisfaction with breasts." CONCLUSION: Both the aesthetic/surgery-related and psychological aspects are equally important with regard to "satisfaction with breasts" after BCT. The data could serve as the benchmark for future studies.

Evaluation of the FUSION-X-US-II prototype to combine automated breast ultrasound and tomosynthesis.

OBJECTIVE: The FUSION-X-US-II prototype was developed to combine 3D automated breast ultrasound (ABUS) and digital breast tomosynthesis in a single device. We evaluated the performance of ABUS and tomosynthesis in a single examination in a clinical setting. METHODS: In this prospective feasibility study, digital breast tomosynthesis and ABUS were performed using the FUSION-X-US-II prototype without any change of the breast position in patients referred for clarification of breast lesions with an indication for tomosynthesis. The tomosynthesis and ABUS images of the prototype were interpreted independently from the clinical standard by a breast diagnostics specialist. Any detected lesion was classified using BI-RADS® scores, and results of the standard clinical routine workup (gold standard) were compared to the result of the separate evaluation of the prototype images. Image quality was rated subjectively and coverage of the breast was measured. RESULTS: One hundred one patients received both ABUS and tomosynthesis using the prototype. The duration of the additional ABUS acquisition was 40 to 60 s. Breast coverage by ABUS was approximately 80.0%. ABUS image quality was rated as diagnostically useful in 86 of 101 cases (85.1%). Thirty-three of 34 malignant breast lesions (97.1%) were identified using the prototype. CONCLUSION: The FUSION-X-US-II prototype allows a fast ABUS scan in combination with digital breast tomosynthesis in a single device integrated in the clinical workflow. Malignant breast lesions can be localized accurately with direct correlation of ABUS and tomosynthesis images. The FUSION system shows the potential to improve breast cancer screening in the future after further technical improvements. KEY POINTS: • The FUSION-X-US-II prototype allows the combination of automated breast ultrasound and digital breast tomosynthesis in a single device without decompression of the breast. • Image quality and coverage of ABUS are sufficient to accurately detect malignant breast lesions. • If tomosynthesis and ABUS should become part of breast cancer screening, the combination of both techniques in one device could offer practical and logistic advantages. To evaluate a potential benefit of a combination of ABUS and tomosynthesis in screening-like settings, further studies are needed.

Outcomes of Return to Routine Screening for BI-RADS 3 Lesions Detected at Supplemental Automated Whole-Breast Ultrasound in Women With Dense Breasts: A Prospective Study.

BACKGROUND. Supplemental screening breast ultrasound (US) detects additional cancers in women with dense breasts but identifies many BI-RADS 3 lesions that result in short-term follow-up and biopsies. OBJECTIVE. The purpose of this study was to evaluate outcomes in patients recommended for return to routine screening for lesions assessed as BI-RADS 3 on supplemental automated whole-breast US. METHODS. This prospective study invited patients with BI-RADS 1 or 2 on screening mammography and breast density C or D to undergo supplemental automated breast US (ABUS). ABUS was interpreted as BI-RADS 1, 2, 3, or 0. Return to routine screening was recommended for ABUS BI-RADS 1, 2, or 3. ABUS BI-RADS 0 lesions underwent targeted handheld US. Remaining patients were followed for 2 years. Malignancy rates were compared using Fisher exact tests. RESULTS. A total of 2257 women (mean age, 58.0 ± 11.2 [SD] years) were included. Supplemental ABUS was scored as BI-RADS 1 in 1186 (52.5%) women, BI-RADS 2 in 591 (26.2%), BI-RADS 3 in 395 (17.5%), and BI-RADS 0 in 85 (3.8%). A total of 394 patients with ABUS BI-RADS 3 had 2-year follow-up, during which no cancer (0%; 95% CI, 0.0-0.9%) was diagnosed in the quadrant of the lesion. Among patients with 2-year follow-up, breast cancer was diagnosed in 4/1117 (0.4%) with ABUS BI-RADS 1, 2/556 (0.4%) with ABUS BI-RADS 2, and 2/394 (0.5%) with ABUS BI-RADS 3 (cancer in other quadrant than the lesion). Malignancy rates were not different between ABUS BI-RADS 1, 2, and 3 (p = .28). The ABUS recall rate was 3.8% (85/2257; 95% CI, 3.6-4.0%). If short-term follow-up had been recommended for ABUS BI-RADS 3, the ABUS recall rate would have been 21.3% (480/2257, 95% CI 19.6-23.0%). The biopsy rate was 0.5% (12/2257; 95% CI, 0.3-0.9%); the positive biopsy rate was 58.3% (7/12). One of seven cancers diagnosed by initial supplemental ABUS and none of eight cancers diagnosed during subsequent follow-up were node-positive cancer. CONCLUSION. Return to routine screening for ABUS BI-RADS 3 lesions results in a substantial decrease in recall rate and is unlikely to result in an adverse outcome. CLINICAL IMPACT. This prospective study supports a recommendation for routine annual follow-up for BI-RADS 3 lesions at supplemental ABUS. TRIAL REGISTRATION. ClinicalTrials.gov NCT02650778.