Management of Patients with Breast Biopsy under Anti-Coagulation or Anti-Platelet Therapy: Results of a Survey of German Experts.

Introduction: Pre-therapeutic histologic diagnosis through image-guided core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) for suspicious breast findings is a standard procedure. Despite the moderate risk of bleeding, a significant proportion of patients are on temporary or permanent anti-coagulation therapy (ACT) or anti-platelet therapy (APT). Currently, there are no established guidelines for managing biopsies in such patients, leading to varying approaches in clinical practice. Methods: An online survey was conducted among all members of the breast ultrasound working group at the German Society for Ultrasound in Medicine (DEGUM) and the working group for breast diagnostics at the German Radiology Society (DRG). It included n = 51 questions about individual risk perception of biopsy-related bleeding complications and the specific management of biopsies on ACT/APT. Results: A total of 332 experts participated, with 51.8% reporting the absence of a standardized management plan for breast biopsies on ACT/APT. Concerning specific ACT/APT medications, the survey revealed discrepancies in risk perception and management: The majority preferred discontinuing medication with directly acting oral anti-coagulants (DOACs; CNB: 66.9%; VAB: 91.1%), phenprocoumon (CNB: 74.9%; VAB: 96.7%), or therapeutic heparin (CNB: 46.1%; VAB: 72.7%). However, there was a lower inclination to discontinue acetylsalicylic acid (ASA; CNB: 15.2%; VAB: 50.3%) or prophylactic heparin (CNB: 11.9%, VAB: 36.3%). Conclusion: Breast biopsies for patients on ASA or prophylactic heparin are deemed safe and part of standard clinical practice. However, despite available feasibility studies, conducting breast biopsies on ACT medications such as DOACs or phenprocoumon appears feasible only for a minority of experts.

Breast-conserving surgery is not associated with increased local recurrence in patients with early-stage node-negative triple-negative breast cancer treated with neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is routinely used for patients with triple-negative breast cancer (TNBC). Upfront breast-conserving therapy (BCT) consisting of breast-conserving surgery (BCS) and adjuvant radiotherapy (RT) has been shown to be associated with improved outcome in patients with early TNBC as compared to mastectomy. METHODS: We identified 2632 patients with early TNBC from the German Breast Group meta-database. Patients with cT1-2 cN0 and ypN0, available surgery and follow-up data were enrolled. Data of 1074 patients from 8 prospective NACT trials were available. Endpoints of interest were locoregional recurrence as first site of relapse (LRR), disease-free survival (DFS) and overall survival (OS). We performed univariate and multivariate Fine-Gray analysis and Cox regression models. RESULTS: After a median follow-up of 64 months, there were 94 (8.8%) locoregional events as first site of relapse. Absence of pathologic complete response (pCR) was associated with increased LRR upon uni- and multivariate analysis (hazard ratio [HR] = 2.28; p < 0.001 and HR = 2.22; p = 0.001). Type of surgery was not associated with LRR. Patients in the BCS-group had better DFS and OS (DFS: HR = 0.47; p < 0.001 and OS: HR = 0.40; p < 0.001). BCS was associated with improved DFS and OS upon multivariate analysis (DFS: HR = 0.51; p < 0.001; and OS HR = 0.43; p < 0.001), whereas absence of pCR was associated with worse DFS and OS (DFS: HR = 2.43; p < 0.001; and OS: HR = 3.15; p < 0.001). CONCLUSIONS: In this retrospective analysis of patients with early stage node-negative TNBC treated with NACT, BCS was not associated with an increased risk of LRR but with superior DFS and OS.

Incidence and Risk Assessment of Capsular Contracture in Breast Cancer Patients following Post-Mastectomy Radiotherapy and Implant-Based Reconstruction.

Our study aims to identify the risk factors and dosimetry characteristics associated with capsular contracture. METHODS: We retrospectively analyzed 118 women with breast cancer who underwent PMRT following an IBR between 2010 and 2022. Patients were treated with PMRT of 50.0-50.4 Gy in 25-28 fractions. Capsular contracture was categorized according to the Baker Classification for Reconstructed Breasts. RESULTS: After a median follow-up of 22 months, the incidence of clinically relevant capsular contracture (Baker III-IV) was 22.9%. Overall, capsular contracture (Baker I-IV) occurred in 56 patients (47.5%) after a median of 9 months after PMRT. The rate of reconstruction failure/implant loss was 25.4%. In the univariate analysis, postoperative complications (prolonged pain, prolonged wound healing, seroma and swelling) and regional nodal involvement were associated with higher rates of capsular contracture (p = 0.017, OR: 2.5, 95% CI: 1.2-5.3 and p = 0.031, respectively). None of the analyzed dosimetric factors or the implant position were associated with a higher risk for capsular contracture. CONCLUSION: Postoperative complications and regional nodal involvement were associated with an increased risk of capsular contracture following breast reconstruction and PMRT, while none of the analyzed dosimetric factors were linked to a higher incidence. Additional studies are needed to identify further potential risk factors.

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.

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.

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.

Deep learning to predict breast cancer sentinel lymph node status on INSEMA histological images.

BACKGROUND: Sentinel lymph node (SLN) status is a clinically important prognostic biomarker in breast cancer and is used to guide therapy, especially for hormone receptor-positive, HER2-negative cases. However, invasive lymph node staging is increasingly omitted before therapy, and studies such as the randomised Intergroup Sentinel Mamma (INSEMA) trial address the potential for further de-escalation of axillary surgery. Therefore, it would be helpful to accurately predict the pretherapeutic sentinel status using medical images. METHODS: Using a ResNet 50 architecture pretrained on ImageNet and a previously successful strategy, we trained deep learning (DL)-based image analysis algorithms to predict sentinel status on hematoxylin/eosin-stained images of predominantly luminal, primary breast tumours from the INSEMA trial and three additional, independent cohorts (The Cancer Genome Atlas (TCGA) and cohorts from the University hospitals of Mannheim and Regensburg), and compared their performance with that of a logistic regression using clinical data only. Performance on an INSEMA hold-out set was investigated in a blinded manner. RESULTS: None of the generated image analysis algorithms yielded significantly better than random areas under the receiver operating characteristic curves on the test sets, including the hold-out test set from INSEMA. In contrast, the logistic regression fitted on the Mannheim cohort retained a better than random performance on INSEMA and Regensburg. Including the image analysis model output in the logistic regression did not improve performance further on INSEMA. CONCLUSIONS: Employing DL-based image analysis on histological slides, we could not predict SLN status for unseen cases in the INSEMA trial and other predominantly luminal cohorts.

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.

Prevalence of Pathogenic Germline Variants in Women with Non-Familial Unilateral Triple-Negative Breast Cancer.

Introduction: International guidelines recommend genetic testing for women with familial breast cancer at an expected prevalence of pathogenic germline variants (PVs) of at least 10%. In a study sample of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), we have previously shown that women with TNBC diagnosed before the age of 50 years but without a family history of breast or ovarian cancer (sTNBC) meet this criterion. The present study investigates the PV prevalence in BRCA1, BRCA2, and nine additional cancer predisposition genes in an extended sTNBC study sample including a cohort of women with a later age at sTNBC diagnosis. Patients and Methods: In 1,600 women with sTNBC (median age at diagnosis: 41 years, range 19-78 years), we investigated the association between age at diagnosis and PV occurrence in cancer predisposition genes using logistic regression. Results: 260 sTNBC patients (16.2%) were found to have a PV in cancer predisposition genes (BRCA1: n = 170 [10.6%]; BRCA2: n = 46 [2.9%], other: n = 44 [2.8%]). The PV prevalence in women diagnosed between 50 and 59 years (n = 194) was 11.3% (22/194). Logistic regression showed a significant increase in PV prevalence with decreasing age at diagnosis (OR 1.41 per 10 years younger age at diagnosis; 95% confidence interval: 1.21-1.65; p < 0.001). The PV prevalence predicted by the model was above 10% for diagnoses before the age of 56.8 years. Conclusion: Based on the data presented, we recommend genetic testing by gene panel analysis for sTNBC patients diagnosed before the age of 60 years. Due to the still uncertain estimate for women with sTNBC diagnosed above the age of 60 years, further studies are needed.

Noninferiority of Local Control and Comparable Toxicity of Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost in Breast Cancer: 5-Year Results of the IMRT-MC2 Phase III Trial.

PURPOSE: The IMRT-MC2 trial was conducted to demonstrate the noninferiority of conventionally fractionated intensity modulated radiation therapy with a simultaneous integrated boost to 3-dimensional conformal radiation therapy with a sequential boost for adjuvant breast radiation therapy. METHODS AND MATERIALS: A total of 502 patients were randomized between 2011 and 2015 for the prospective, multicenter, phase III trial (NCT01322854). Five-year results of late toxicity (late effects normal tissue task force-subjective, objective, management, and analytical), overall survival, disease-free survival, distant disease-free survival, cosmesis (Harvard scale), and local control (noninferiority margin at hazard ratio [HR] of 3.5) were analyzed after a median follow-up of 62 months. RESULTS: The 5-year local control rate for the intensity modulated radiation therapy with simultaneous integrated boost arm was non-inferior to the control arm (98.7% vs 98.3%, respectively; HR, 0.582; 95% CI, 0.119-2.375; P = .4595). Furthermore, there was no significant difference in overall survival (97.1% vs 98.3%, respectively; HR, 1.235; 95% CI, 0.472-3.413; P = .6697), disease-free survival (95.8% vs 96.1%, respectively; HR, 1.130; 95% CI, 0.487-2.679; P = .7758), and distant disease-free survival (97.0% vs 97.8%, respectively; HR, 1.667; 95% CI, 0.575-5.434; P = .3601). After 5 years, late toxicity evaluation and cosmetic assessment further showed no significant differences between treatment arms. CONCLUSIONS: The 5-year results of the IMRT-MC2 trial provide strong evidence that the application of conventionally fractionated simultaneous integrated boost irradiation for patients with breast cancer is both safe and effective, with noninferior local control compared with 3-dimensional conformal radiation therapy with sequential boost.

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.

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.

Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscopy 'Histolog® scanner' for breast margin assessment in comparison with conventional specimen radiography.

PURPOSE: The Histolog® Scanner (SamanTree Medical SA, Lausanne, Switzerland) is a large field-of-view confocal laser scanning microscope designed to allow intraoperative margin assessment by the production of histological images ready for assessment in the operating room. We evaluated the feasibility and the performance of the Histolog® Scanner (HS) to correctly identify infiltrated margins in clinical practice of lumpectomy specimens. It was extrapolated if the utilization of the HS has the potential to reduce infiltrated margins and therefore reduce re-operation rates in patients undergoing breast conserving surgery (BCS) due to a primarily diagnosed breast cancer including ductal carcinoma in situ. METHODS: This is a single-center, prospective, non-interventional, diagnostic pilot study including 50 consecutive patients receiving BCS. The complete surface of the specimen was scanned using the HS intraoperatively. The surgery and the intraoperative margin assessment of the specimen was performed according to the clinical routine consisting of conventional specimen radiography as well as the clinical impression of the surgeon. Three surgeons and an experienced pathologist assessed the scans produced by the HS for cancer cells on the surface. The potential of the HS to correctly identify involved margins was compared to the results of the conventional specimen radiography alone as well as the clinical routine. The histopathological report served as the gold standard. RESULTS: 50 specimens corresponding to 300 surfaces were scanned by the HS. The mean sensitivity of the surgeons to identify involved margins with the HS was 37.5% ± 5.6%, the specificity was 75.2% ± 13.0%. The assessment of resection margins by the pathologist resulted in a sensitivity of 37.5% and a specificity of 81.0%, while the local clinical routine resulted in a sensitivity of 37.5% and a specificity of 78.2%. CONCLUSION: Acquisition of high-resolution histological images using the HS was feasible in clinical practice. Sensitivity and specificity were comparable to clinical routine. With more specific training and experience on image interpretation and acquisition, the HS may have the potential to enable more accuracy in the margin assessment of BCS specimens.

Clinical prototype implementation enabling an improved day-to-day mammography compression.

PURPOSE: In mammography, breast compression is achieved by lowering a compression paddle on the breast. Despite the directive that compression is needed, there is no concrete guideline on its execution. To estimate the degree of compression, current mammography units only provide compression force and breast thickness as parameters. Therefore, radiographers could be induced to mainly determine the level of compression based on compression force and apply the same value to all breast sizes. In this case, smaller breast sizes are exposed to higher pressure. This results in a highly varying perception of discomfort or even pain during the procedure, depending on the breast size. METHODS: To overcome this imbalance, current research results suggest that pressure might be a more qualified parameter for a more uniform compression among all breast sizes. To utilize pressure, the contact area between breast and compression paddle must be determined. In this paper, we present an easy-to-implement prototype enabling a real-time pressure-based measure without the need of direct patient contact. Using an optical camera, the contact area between the breast and the compression paddle is automatically segmented by a deep learning model. RESULTS: The model provides a mean pixel accuracy of 96.7% (SD: 2.3%), mean frequency-weighted intersection over union of 88.5% (SD: 6.3%), and a Dice score of 93.6% (SD: 2.2%). The subsequent pressure display is updated more than five times per second which enables the use in clinical routines to set the compression level. CONCLUSION: This prototype could help guiding to an improved breast compression routine in mammography procedures.

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.

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).

Patient-reported outcomes for the Intergroup Sentinel Mamma study (INSEMA): A randomised trial with persistent impact of axillary surgery on arm and breast symptoms in patients with early breast cancer.

Background: In clinically node-negative breast cancer patients, the INSEMA trial (NCT02466737) assessed the non-inferiority of avoiding sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Here we present patient-reported outcomes (PROs) as a secondary endpoint. Methods: PROs were assessed for patients with no axillary surgery, SLNB alone, and ALND. Quality of life (QoL) questionnaire EORTC QLQ-C30 and its breast cancer module (BR23) were used at baseline (pre-surgery) and 1, 3, 6, 12, and 18 months after surgery. The QoL scores were compared using repeated measures mixed models based on the safety set. Findings: Between 2015 and 2019, 5502 patients were recruited for the first randomization, and 5154 were included in the intent-to-treat set (4124 SLNB versus 1030 no SLNB). In the case of one to three macrometastases after SLNB, 485 patients underwent second randomization (242 SLNB alone versus 243 ALND). Questionnaire completion response remained high throughout the trial: over 70% at all time points for the first randomization. There were significant differences for the BRBS (breast symptoms) and BRAS (arm symptoms) scores favoring the no SLNB group in all post-baseline assessments. Patients in the SLNB group showed significantly and clinically relevant higher scores for BRAS (differences in mean values ≥5.0 points at all times), including pain, arm swelling, and impaired mobility in all postoperative visits, with the highest difference at one month after surgery. Scoring of the QLQ-C30 questionnaire revealed no relevant differences between the treatment groups, although some comparisons were statistically significant. Interpretation: This is one of the first randomized trials investigating the omission of SLNB in clinically node-negative patients and the first to report comprehensive QoL data. Patients with no SLNB benefitted regarding arm symptoms/functioning, while no relevant differences in other scales were seen. Funding: Supported by German Cancer Aid (Deutsche Krebshilfe, Bonn, Germany), Grant No. 110580 and Grant No. 70110580 to University Medicine Rostock.