Treatment and survival of patients diagnosed with high-risk HR+/HER2- breast cancer in the Netherlands: a population-based retrospective cohort study.

BACKGROUND: Several factors may increase the risk of recurrence of patients diagnosed with hormone receptor-positive human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC). We aim to determine the proportion of patients with high-risk HR+/HER2- BC within the total HR+/HER2- BC cohort and compare their systemic treatments and survival rates with those of patients with low- and intermediate-risk HR+/HER2- BC and triple-negative (TN) BC. PATIENTS AND METHODS: Women diagnosed with nonmetastatic invasive HR+/HER2- BC and TNBC in the Netherlands between 2011 and 2019 were identified from the Netherlands Cancer Registry. Patients with HR+/HER2- BC were categorised according to risk profile, defined by nodal status, tumour size, and histological grade. High-risk HR+/HER2- BC was defined by either four or more positive lymph nodes or one to three positive lymph nodes with a tumour size of ≥5 cm or a histological grade 3 tumour. Overall survival (OS) and relative survival (RS) were calculated using the Kaplan-Meier and Pohar-Perme method. RESULTS: In this study of 87 455 patients with HR+/HER2- BC, 44 078 (50%) patients were diagnosed with low risk, 28 452 (33%) with intermediate risk, and 11 285 (13%) with high-risk HR+/HER2- BC. In 3640 (4%) patients, the risk profile could not be defined. Endocrine therapy and chemotherapy were used in 38% and 7% of low-risk, 90% and 47% of intermediate-risk, and 94% and 73% of high-risk patients, respectively. The 10-year OS and RS rates were 84.1% [95% confidence interval (95% CI) 83.5% to 84.7%] and 98.7% (95% CI 97.3% to 99.4%) in low-risk, 75.1% (95% CI 74.2% to 76.0%) and 91.7% (95% CI 89.7% to 93.3%) in intermediate-risk, and 63.4% (95% CI 62.0% to 64.7%) and 72.3% (70.1% to 74.3%) in high-risk patients. The 10-year OS and RS rates of 12 689 patients with TNBC were 69.7% (95% CI 68.6% to 70.8%) and 79.1% (95% CI 77.0% to 80.9%), respectively. CONCLUSION: The poor prognosis of patients with high-risk HR+/HER2- BC highlights the need for a better acknowledgement of this subgroup and supports ongoing clinical trials aimed at optimising systemic therapy.

The role of contrast-enhanced mammography in the preoperative evaluation of invasive lobular carcinoma of the breast.

AIM: To assess the performance of contrast-enhanced mammography (CEM) in the preoperative staging of invasive lobular carcinoma (ILC) of the breast. MATERIALS AND METHODS: The present study was a multicentre, multivendor, multinational retrospective study of women with a histological diagnosis of ILC who had undergone CEM from December 2013 to December 2021. Index lesion size and multifocality were recorded for two-dimensional (2D) mammography, CEM, and when available magnetic resonance imaging (MRI). Comparison with histological data was undertaken for women treated by primary surgical excision. Pearson correlation coefficients and Bland-Altman's analysis of agreement were used to assess differences with a significance level of 0.05. RESULTS: One hundred and fifteen ILC lesions were included, 46 (40%) presented symptomatically and 69 were screening detected. CEM demonstrated superior sensitivity when compared to standard mammography. The correlation between the histological size measured on the surgical excision specimen size was greater than with standard mammography (r=0.626 and 0.295 respectively, p=0.001), with 19% of lobular carcinomas not visible without a contrast agent. The sensitivity of CEM for multifocal disease was greater than standard mammography (70% and 20% respectively, p<0.0001). CEM overestimated tumour size by an average of 1.5 times, with the size difference increasing for larger tumour. When MRI was performed (n=22), tumour size was also overestimated by an average of 1.3 times. The degree of size overestimation was similar for both techniques, with the tumour size on CEM being on average 0.5 cm larger than MRI. CONCLUSION: CEM is a useful tool for the local staging of lobular carcinomas and could be an alternative to breast MRI.

Contrast-enhanced breast imaging: Current status and future challenges.

BACKGROUND: Contrast-enhanced breast MRI and recently also contrast-enhanced mammography (CEM) are available for breast imaging. The aim of the current overview is to explore existing evidence and ongoing challenges of contrast-enhanced breast imaging. METHODS: This narrative provides an introduction to the contrast-enhanced breast imaging modalities breast MRI and CEM. Underlying principle, techniques and BI-RADS reporting of both techniques are described and compared, and the following indications and ongoing challenges are discussed: problem-solving, high-risk screening, supplemental screening in women with extremely dense breast tissue, breast implants, neoadjuvant systemic therapy (NST) response monitoring, MRI-guided and CEM- guided biopsy. RESULTS: Technique and reporting for breast MRI are standardised, for the newer CEM standardisation is in progress. Similarly, compared to other modalities, breast MRI is well established as superior for problem-solving, screening women at high risk, screening women with extremely dense breast tissue or with implants; and for monitoring response to NST. Furthermore, MRI-guided biopsy is a reliable technique with low long-term false negative rates. For CEM, data is as yet either absent or limited, but existing results in these settings are promising. CONCLUSION: Contrast-enhanced breast imaging achieves highest diagnostic performance and should be considered essential. Of the two contrast-enhanced modalities, evidence of breast MRI superiority is ample, and preliminary results on CEM are promising, yet CEM warrants further study.

Overview of trials on artificial intelligence algorithms in breast cancer screening - A roadmap for international evaluation and implementation.

Accumulating evidence from retrospective studies demonstrate at least non-inferior performance when using AI algorithms with different strategies versus double-reading in mammography screening. In addition, AI algorithms for mammography screening can reduce work load by moving to single human reading. Prospective trials are essential to avoid unintended adverse consequences before incorporation of AI algorithms into UK's National Health Service (NHS) Breast Screening Programme (BSP). A stakeholders' meeting was organized in Newnham College, Cambridge, UK to undertake a review of the current evidence to enable consensus discussion on next steps required before implementation into a screening programme. It was concluded that a multicentre multivendor testing platform study with opt-out consent is preferred. AI thresholds from different vendors should be determined while maintaining non-inferior screening performance results, particularly ensuring recall rates are not increased. Automatic recall of cases using an agreed high sensitivity AI score versus automatic rule out with a low AI score set at a high sensitivity could be used. A human reader should still be involved in decision making with AI-only recalls requiring human arbitration. Standalone AI algorithms used without prompting maintain unbiased screening reading performance, but reading with prompts should be tested prospectively and ideally provided for arbitration.

Axillary lymph node response to neoadjuvant systemic therapy with dedicated axillary hybrid 18F-FDG PET/MRI in clinically node-positive breast cancer patients: a pilot study.

AIM: To investigate the diagnostic performance of dedicated axillary hybrid 18F-2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) in detecting axillary pathological complete response (pCR) following neoadjuvant systemic therapy (NST) in clinically node-positive breast cancer patients. MATERIALS AND METHODS: Ten prospectively included clinically node-positive breast cancer patients underwent dedicated axillary hybrid 18F-FDG PET/MRI after completing NST followed by axillary surgery. PET images were reviewed by a nuclear medicine physician and coronal T1-weighted and T2-weighted MRI images by a radiologist. All axillary lymph nodes visible on PET/MRI were matched with those removed during axillary surgery. Diagnostic performance parameters were calculated based on patient-by-patient and node-by-node validation with histopathology of the axillary surgical specimen as the reference standard. RESULTS: Six patients achieved axillary pCR at final histopathology. A total of 84 surgically harvested axillary lymph nodes were matched with axillary lymph nodes depicted on PET/MRI. Histopathological examination of the matched axillary lymph nodes resulted in 10 lymph nodes with residual axillary disease of which eight contained macrometastases and two micrometastases. The patient-by-patient analysis yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 25%, 100%, 100%, and 67%, respectively. The diagnostic performance parameters of the node-by-node analysis were 0%, 96%, 0%, and 88%, respectively. Excluding micrometastases from the node-by-node analysis increased the negative predictive value to 90%. CONCLUSION: This pilot study suggests that the negative predictive value and sensitivity of dedicated axillary 18F-FDG PET/MRI are insufficiently accurate to detect axillary pCR or exclude residual axillary disease following NST in clinically node-positive breast cancer patients.

Axillary lymph node characteristics in breast cancer patients versus post-COVID-19 vaccination: Overview of current evidence per imaging modality.

BACKGROUND: Axillary lymph node characteristics on axillary ultrasound (US), breast MRI and 18F-FDG PET/CT are relevant at breast cancer diagnosis. Axillary lymphadenopathy after COVID-19 vaccination has been frequently reported. This may cause a diagnostic dilemma, particularly in the ipsilateral axilla in women who have a either a recent diagnosis of breast cancer or a history of breast cancer. This review provides an overview of the current evidence regarding axillary lymph node characteristics at breast cancer diagnosis versus "post-COVID-19 vaccination". METHODS: A non-systematic narrative review was performed. Studies describing axillary lymph node characteristics per imaging modality (axillary US, breast MRI and 18F-FDG PET/CT) in breast cancer patients versus post-COVID-19 vaccination were selected and used for the current study. RESULTS: The morphologic characteristics and distribution of abnormal nodes on US may differ from the appearance of metastatic adenopathy since diffuse cortical thickening of the lymph nodes is the most observed characteristic after vaccination, whereas metastases show as most suspicious characteristics focal cortical thickening and effacement of the fatty hilum. Current evidence on MRI and 18F-FDG on morphologic characteristics of axillary lymphadenopathy is missing, although it was suggested that vaccine related lymphadenopathy is more likely to be present in level 2 and 3 nodes than metastatic nodes. Reported frequencies of lymphadenopathy post-COVID-19 vaccination range from 49% to 85% (US), 29% (breast MRI) and 14.5% to 53.9% (18F-FDG PET/CT). Several factors may impact the presence or extent of lymphadenopathy post-COVID-19 vaccination: injection site, type of vaccine (i.e., mRNA versus vector), time interval (days) between vaccination and imaging, previous history of COVID-19 pneumonia, and first versus second vaccine dose. CONCLUSION: Although lymph node characteristics differ at breast cancer diagnosis versus post-COVID-19 vaccination, clinical information regarding injection site, vaccine type and vaccination date needs to be documented to improve the interpretation and guide treatment towards the next steps of action.

The percentage of residual DCIS in patients diagnosed with primary invasive breast cancer treated with neoadjuvant systemic therapy: A nationwide retrospective study.

INTRODUCTION: Neoadjuvant systemic therapy (NST) is increasingly applied in breast cancer to improve surgical and oncological outcome. Approximately 21% of patients receiving NST achieve pathological complete response (pCR) of the breast. There is disagreement on the definition of pCR with respect to residual DCIS (ypT0 versus ypT0/is). The aim of this retrospective study was to determine the percentage of breast pCR (ypT0) and residual DCIS (ypTis), and its association with clinicopathological variables, in patients treated with NST and surgery. MATERIALS AND METHODS: Patients with invasive breast cancer treated with neoadjuvant chemotherapy, with or without targeted therapy, in the period of 2010-2019 were selected from the Netherlands Cancer Registry (NCR). Descriptive statistics and multivariable logistic regression analyses were used to analyse the percentage of ypT0 and ypTis and its association with clinicopathological variables. RESULTS: From the NCR database, 20495 patients were included, of whom 5847 (28.5%) achieved breast pCR (ypT0) and 881 (4.3%) showed residual DCIS (ypTis). The percentage of ypTis was highest in HER2+ tumour subtypes (ER+HER2+ 7.9%, ER-HER2+ 9.8%, ER+HER2- 2.1%, triple negative 3.3%, p < 0.001). Multivariable logistic regression analyses demonstrated high tumour grade (OR 2.00, p = 0.003) and HER2+ tumour subtype (ER+HER2+ OR 3.58, ER-HER2+ OR 4.37, p < 0.001) as independent predictors for ypTis. CONCLUSION: pCR (ypT0) was achieved in 5847 (28.5%) patients receiving NST and residual DCIS (ypTis) was found in 881 (4.3%) patients. Consequently, the rate of pCR may be affected by ypTis when not excluded from the definition. The percentage of ypTis is highest in HER2+ subtypes.

Contrast enhanced mammography (CEM) versus magnetic resonance imaging (MRI) for staging of breast cancer: The pro CEM perspective.

In women with newly diagnosed breast cancer, preoperative staging is required to assess disease extent, enabling us to decide on the most optimal treatment strategy. For locoregional staging, assessment of intramammary tumor extent and presence of axillary and perhaps also internal mammary lymph node metastases is required. Due to the similarity in the underlying principle, contrast-enhanced mammography is increasingly considered instead of breast MRI for this purpose. When considering the combination of CEM and US as a single appointment imaging strategy for preoperative staging of breast cancer, there is only limited room for an additional benefit of breast MRI. For tumor size measurements, equal performance of both CEM and MRI are observed. Sensitivity of both techniques for detecting breast cancer is comparable, meaning that both techniques are capable of detecting additional ipsilateral or contralateral tumor foci. However, specificity is in favor of CEM, meaning that there is a slightly lower chance of having false positive findings in preoperative staging of the breast. Axillary US can be performed during the same appointment as CEM, with equal performance and limitations as evaluation of the axilla on standard breast MRI examinations. Finally, there is no need to actively pursue the detection of IMLN metastases, meaning that additional MRI to do so is not required. This review provides a 'pro-CEM' perceptive on the arguments why breast MRI is hardly necessary when CEM in combination with US has been performed as a single appointment imaging strategy in breast cancer patients.

Conditional local recurrence risk: the effect of event-free years in different subtypes of breast cancer.

BACKGROUND: After breast cancer treatment, follow-up consists of physical examination and mammography for at least 5 years, to detect local and regional recurrence. The risk of recurrence may decrease after event-free time. This study aims to determine the risk of local recurrence (LR) as a first event until 5 years after diagnosis, conditional on being event-free for 1, 2, 3 and 4 years. METHODS: From the Netherlands Cancer Registry, all M0 breast cancers diagnosed between 2005 and 2008 were included. LR risk was calculated with Kaplan-Meier analysis, overall and for different subtypes. Conditional LR (assuming x event-free years) was determined by selecting event-free patients at x years, and calculating their LR risk within 5 years after diagnosis. RESULTS: Five-year follow-up was available for 34,453 patients. Overall, five-year LR as a first event occurred in 3.0%. This risk varied for different subtypes and was highest for triple negative (6.8%) and lowest for ER+PR+Her2- (2.2%) tumors. After 1, 2, 3 and 4 event-free years, the average risk of LR before 5 years after diagnosis decreased from 3.0 to 2.4, 1.6, 1.0, and 0.6%. The risk decreased in all subtypes, the effect was most pronounced in subtypes with the highest baseline risk (ER-Her2+ and triple negative breast cancer). After three event-free years, LR risk in the next 2 years was 1% or less in all subtypes except triple negative (1.6%). CONCLUSION: The risk of 5-year LR as a first event was low and decreased with the number of event-free years. After three event-free years, the overall risk was 1%. This is reassuring to patients and also suggests that follow-up beyond 3 years may produce low yield of LR, both for individual patients and studies using LR as primary outcome. This can be used as a starting point to tailor follow-up to individual needs.

The effect of breast MRI on disease-free and overall survival in breast cancer patients: a retrospective population-based study.

PURPOSE: To evaluate the effect of breast MRI on overall survival (OS) and disease-free survival (DFS) of patients with invasive breast cancer in the Netherlands. METHODS: We selected all women from the Netherlands Cancer Registry diagnosed with invasive breast cancer (a) between 2011 and 2013 for the OS-cohort and (b) in the first quarter of 2012 for the DFS-cohort. The study population was subdivided into an MRI and non-MRI group. In addition, subgroups were created according to breast cancer subtype: invasive carcinoma of no special type (NST) versus invasive lobular carcinoma (ILC). OS and DFS were compared between the MRI and non-MRI group using the Kaplan-Meier method and the log-rank test. Cox proportional hazard regression analysis was performed to estimate hazard ratios (HR) with a 95% confidence interval (CI). To account for missing data, multiple imputation was performed. RESULTS: Of the 31,756 patients included in the OS-cohort (70% non-MRI and 30% MRI), 27,752 (87%) were diagnosed with invasive carcinoma NST and 4004 (13%) with ILC. Of the 2464 patients included in the DFS-cohort (72% non-MRI and 28% MRI), 2161 (88%) were diagnosed with invasive carcinoma NST and 303 (12%) with ILC. The distribution of breast MRI use was significantly lower over different age categories, from 49.0% aged < 50 to 16.5% aged > 70. Multivariable Cox regression showed that breast MRI was not significantly associated with OS overall (HR 0.91, 95%-CI 0.74-1.11, p = 0.35), nor in the different histological subtypes. Multivariable Cox regression analysis showed that breast MRI was also not significantly associated with DFS (HR 1.16, 95%-CI 0.81-1.67), nor in the different histological subtypes. CONCLUSION: Use of breast MRI was not significantly associated with an improved OS or DFS in patients treated with primary surgery.

MRI-based radiomics in breast cancer: feature robustness with respect to inter-observer segmentation variability.

Radiomics is an emerging field using the extraction of quantitative features from medical images for tissue characterization. While MRI-based radiomics is still at an early stage, it showed some promising results in studies focusing on breast cancer patients in improving diagnoses and therapy response assessment. Nevertheless, the use of radiomics raises a number of issues regarding feature quantification and robustness. Therefore, our study aim was to determine the robustness of radiomics features extracted by two commonly used radiomics software with respect to variability in manual breast tumor segmentation on MRI. A total of 129 histologically confirmed breast tumors were segmented manually in three dimensions on the first post-contrast T1-weighted MR exam by four observers: a dedicated breast radiologist, a resident, a Ph.D. candidate, and a medical student. Robust features were assessed using the intraclass correlation coefficient (ICC > 0.9). The inter-observer variability was evaluated by the volumetric Dice Similarity Coefficient (DSC). The mean DSC for all tumors was 0.81 (range 0.19-0.96), indicating a good spatial overlap of the segmentations based on observers of varying expertise. In total, 41.6% (552/1328) and 32.8% (273/833) of all RadiomiX and Pyradiomics features, respectively, were identified as robust and were independent of inter-observer manual segmentation variability.

Patterns of axillary staging and management in clinically node positive breast cancer patients treated with neoadjuvant systemic therapy: Results of a survey amongst breast cancer specialists.

INTRODUCTION: Various options for axillary staging after neoadjuvant systemic therapy (NST) are available for breast cancer patients with a clinically positive axillary node (cN+). This survey assessed current practices amongst breast cancer specialists. MATERIALS AND METHODS: A survey was performed amongst members of the European Society of Surgical Oncology and two UK-based Associations: the Association of Breast Surgery and the British Association of Surgical Oncology. The survey included 3 parts: 1. general information, 2. diagnostic work-up and 3. axillary staging after NST. RESULTS: A total of 310 responses were collected: parts 1, 2 and 3 were fully completed by 282 (91%), 270 (87.1%) and 225 (72.6%) respondents respectively. After NST, 153/267 (57.3%) respondents currently perform ALND routinely and 114 (42.7%) respondents perform less invasive restaging of the axilla with possible omission of ALND. In the latter group, 85% does and 15% does not use nodal response seen on imaging to guide the axillary restaging procedure. Regarding respondents that do use imaging: 95% would perform a less invasive staging procedure in case of complete nodal response on imaging (63% sentinel lymph node biopsy (SLNB), excision of a previously marked positive node with SLNB (21%) and without SLNB (11%)). In case of no nodal response on imaging 77% would perform ALND. CONCLUSION: Current axillary staging and management practices in cN + patients after NST vary widely. To determine optimal axillary staging and management in terms of quality of life and oncologic safety, breast specialists are encouraged to include patients in clinical trials/prospective registries.

Rapid Access to Contrast-Enhanced spectral mammogRaphy in women recalled from breast cancer screening: the RACER trial study design.

BACKGROUND: In the Dutch breast cancer screening program, women recalled with a BI-RADS 0 score are referred for additional imaging, while those with BI-RADS 4/5 scores are also directed to an outpatient breast clinic. Approximately six out of ten women are recalled without being diagnosed with a malignancy. However, these recalls require additional imaging and doctor visits, which result in patient anxiety and increased health care costs. Conventional types of imaging used for additional imaging are full-field digital mammography and tomosynthesis. Contrast-enhanced spectral mammography has proved to have higher sensitivity and specificity than conventional imaging in women recalled from screening. Therefore, the aim is to study if CESM instead of conventional imaging is a more accurate, patient-friendly, and cost-effective strategy in the work-up of women recalled from breast cancer screening. METHODS: This prospective, multicenter, randomized controlled trial will be conducted at four centers and will include 528 patients recalled for suspicious breast lesions from the Dutch breast cancer screening program. Participants are randomized in two groups: (1) standard care using conventional breast imaging techniques as initial imaging after recall versus (2) work-up primarily based on CESM. Written informed consent will be collected prior to study inclusion. The primary outcome is the diagnostic accuracy for detection of breast cancer. Secondary outcomes are numbers of additional diagnostic exams, days until final diagnosis, health care costs, and experienced patient anxiety. DISCUSSION: Based on previously published retrospective studies, we expect to demonstrate in this prospective multicenter randomized controlled trial, that using CESM as a primary work-up tool in women recalled from breast cancer screening is a more accurate, cost-effective, and patient-friendly strategy. TRIAL REGISTRATION: Netherlands Trial Register, NL6413/NTR6589. Registered on 6 July, 2017.

Exploring breast cancer response prediction to neoadjuvant systemic therapy using MRI-based radiomics: A systematic review.

PURPOSE: MRI-based tumor response prediction to neoadjuvant systemic therapy (NST) in breast cancer patients is increasingly being studied using radiomics with outcomes that appear to be promising. The aim of this study is to systematically review the current literature and reflect on its quality. METHODS: PubMed and EMBASE databases were systematically searched for studies investigating MRI-based radiomics for tumor response prediction. Abstracts were screened by two reviewers independently. The quality of the radiomics workflow of eligible studies was assessed using the Radiomics Quality Score (RQS). An overview of the methodologies used in steps of the radiomics workflow and current results are presented. RESULTS: Sixteen studies were included with cohort sizes ranging from 35 to 414 patients. The RQS scores varied from 0 % to 41.2 %. Methodologies in the radiomics workflow varied greatly, especially region of interest segmentation, features selection, and model development with heterogeneous outcomes as a result. Seven studies applied univariate analysis and nine studies applied multivariate analysis. Most studies performed their analysis on the pretreatment dynamic contrast-enhanced T1-weighted sequence. Entropy was the best performing individual feature with AUC values ranging from 0.83 to 0.85. The best performing multivariate prediction model, based on logistic regression analysis, scored a validation AUC of 0.94. CONCLUSION: This systematic review revealed large methodological heterogeneity for each step of the MRI-based radiomics workflow, consequently, the (overall promising) results are difficult to compare. Consensus for standardization of MRI-based radiomics workflow for tumor response prediction to NST in breast cancer patients is needed to further improve research.

Diagnostic performance of axillary ultrasound and standard breast MRI for differentiation between limited and advanced axillary nodal disease in clinically node-positive breast cancer patients.

Preoperative differentiation between limited (pN1; 1-3 axillary metastases) and advanced (pN2-3; ≥4 axillary metastases) nodal disease can provide relevant information regarding surgical planning and guiding adjuvant radiation therapy. The aim was to evaluate the diagnostic performance of preoperative axillary ultrasound (US) and breast MRI for differentiation between pN1 and pN2-3 in clinically node-positive breast cancer. A total of 49 patients were included with axillary metastasis confirmed by US-guided tissue sampling. All had undergone breast MRI between 2008-2014 and subsequent axillary lymph node dissection. Unenhanced T2-weighted MRI exams were reviewed by two radiologists independently. Each lymph node on the MRI exams was scored using a confidence scale (0-4) and compared with histopathology. Diagnostic performance parameters were calculated for differentiation between pN1 and pN2-3. Interobserver agreement was determined using Cohen's kappa coefficient. At final histopathology, 67.3% (33/49) and 32.7% (16/49) of patients were pN1 and pN2-3, respectively. Breast MRI was comparable to US in terms of accuracy (MRI reader 1 vs US, 71.4% vs 69.4%, p = 0.99; MRI reader 2 vs US, 73.5% vs 69.4%, p = 0.77). In the case of 1-3 suspicious lymph nodes, pN2-3 was observed in 30.4% on US (positive predictive value (PPV) 69.6%) and in 22.2-24.3% on MRI (PPV 75.7-77.8%). In the case of ≥4 suspicious lymph nodes, pN1 was observed in 33.3% on US (negative predictive value (NPV) 66.7%) and in 38.5-41.7% on MRI (NPV 58.3-61.5%). Interobserver agreement was considered good (k = 0.73). In clinically node-positive patients, the diagnostic performance of axillary US and breast MRI is comparable and limited for accurate differentiation between pN1 and pN2-3. Therefore, there seems no added clinical value of preoperative breast MRI regarding nodal staging in patients with positive axillary US.

Excision of both pretreatment marked positive nodes and sentinel nodes improves axillary staging after neoadjuvant systemic therapy in breast cancer.

BACKGROUND: Marking the axilla with radioactive iodine seed and sentinel lymph node (SLN) biopsy have been proposed for axillary staging after neoadjuvant systemic therapy in clinically node-positive breast cancer. This study evaluated the identification rate and detection of residual disease with combined excision of pretreatment-positive marked lymph nodes (MLNs) together with SLNs. METHODS: This was a multicentre retrospective analysis of patients with clinically node-positive breast cancer undergoing neoadjuvant systemic therapy and the combination procedure (with or without axillary lymph node dissection). The identification rate and detection of axillary residual disease were calculated for the combination procedure, and for MLNs and SLNs separately. RESULTS: At least one MLN and/or SLN(s) were identified by the combination procedure in 138 of 139 patients (identification rate 99·3 per cent). The identification rate was 92·8 per cent for MLNs alone and 87·8 per cent for SLNs alone. In 88 of 139 patients (63·3 per cent) residual axillary disease was detected by the combination procedure. Residual disease was shown only in the MLN in 20 of 88 patients (23 per cent) and only in the SLN in ten of 88 (11 per cent), whereas both the MLN and SLN contained residual disease in the remainder (58 of 88, 66 per cent). CONCLUSION: Excision of the pretreatment-positive MLN together with SLNs after neoadjuvant systemic therapy in patients with clinically node-positive disease resulted in a higher identification rate and improved detection of residual axillary disease.

ANTECEDENTES: En el cáncer de mama con ganglios positivos clínicamente tras el tratamiento neoadyuvante sistémico, se ha propuesto la utilización de iodo radioactivo (Marking Axilla with Radioactive Iodine, MARI) y de la biopsia de ganglio linfático centinela para la estadificación axilar. En este estudio se evaluó la tasa de identificación y detección de enfermedad residual cuando se combinó la exéresis de los ganglios linfáticos marcados antes del tratamiento (marked lymph nodes, MLN) junto con los ganglios centinela (sentinel lymph nodes, SLN). MÉTODOS: Se realizó un análisis retrospectivo multicéntrico de pacientes con cáncer de mama con ganglios positivos clínicamente que se sometieron a tratamiento neoadyuvante sistémico y en las que se combinaron ambas técnicas (con o sin disección axilar). Se calcularon las tasas de identificación y detección de enfermedad residual axilar para MLN y SLN por separado y en conjunto. RESULTADOS: En 138/139 pacientes se identificaron ≥ 1 MLN y/o SLN combinando ambas técnicas (tasa de identificación del 99,3%). La tasa de identificación fue de 92,8% para MLN y del 87,8% para SLN. Combinando ambas técnicas se detectó enfermedad axilar residual en 88/139 (63,3%) pacientes. Se detectó enfermedad residual en 20/88 (22,7%) pacientes utilizando únicamente MLN, en 10/88 (11,4%) pacientes utilizando únicamente SLN y en 58/88 (65,9%) combinando ambas técnicas. CONCLUSIÓN: La exéresis conjunta de los ganglios marcados con iodo radioactivo antes del tratamiento neoadyuvante sistémico y de los ganglios centinela después del tratamiento en pacientes con cN+ logró una tasa de identificación más alta y una mejor detección de la enfermedad axilar residual.

Risk of Positive Sentinel Lymph Node After Neoadjuvant Systemic Therapy in Clinically Node-Negative Breast Cancer: Implications for Postmastectomy Radiation Therapy and Immediate Breast Reconstruction.

BACKGROUND: Residual axillary lymph node involvement after neoadjuvant systemic therapy (NST) is the determining factor for postmastectomy radiation therapy (PMRT). Preoperative identification of patients needing PMRT is essential to enable shared decision-making when choosing the optimal timing of breast reconstruction. We determined the risk of positive sentinel lymph node (SLN) after NST in clinically node-negative (cN0) breast cancer. METHODS: All cT1-3N0 patients treated with NST followed by mastectomy and SLNB between 2010 and 2016 were identified from the Netherlands Cancer Registry. Rate of positive SLN for different breast cancer subtypes was determined. Logistic regression analysis was performed to determine correlated clinicopathological variables with positive SLN. RESULTS: In total 788 patients were included, of whom 25.0% (197/788) had positive SLN. cT1-3N0 ER+HER2+, cT1-3N0 ER-HER2+ , and cT1-2N0 triple-negative patients had the lowest rate of positive SLN: 7.2-11.5%, 0-6.3%, and 2.9-6.2%, respectively. cT1-3N0 ER+HER2- and cT3N0 triple-negative patients had the highest rate of positive SLN: 23.8-41.7% and 30.4%, respectively. Multivariable regression analysis showed that cT2 (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.01-3.96), cT3 (OR 2.56; 95% CI 1.30-5.38), grade 3 (OR 0.44; 95% CI 0.21-0.91), and ER+HER2- subtype (OR 3.94; 95% CI 1.77-8.74) were correlated with positive SLN. CONCLUSIONS: In cT1-3N0 ER+HER2+, cT1-3N0 ER-HER2+, and cT1-2N0 triple-negative patients treated with NST, immediate reconstruction can be considered an acceptable option due to low risk of positive SLN. In cT1-3N0 ER+HER2- and cT3N0 triple-negative patients treated with NST, risks and benefits of immediate reconstruction should be discussed with patients due to the relatively high risk of positive SLN.

Can high school students help to improve breast radiologists in detecting missed breast cancer lesions on full-field digital mammography?

Aim: To investigate whether full-field digital mammography (FFDM) and contrast-enhanced mammography (CEM), evaluated by non-experienced high school students, improves detection of missed breast cancer lesions on FFDM, in the same cohort of patients. Methods: Non-experienced first- and second year high school students examined fourteen cases of patients diagnosed with breast cancer. These cases consisted of missed breast cancer lesions on FFDM by a breast radiologist. Sensitivity of assessment of the students on FFDM and CEM was analysed and compared with the initial results of the breast radiologists. Results: A total of 134 high school students participated in this study. Mean age was 12.8 years (range 10-14). Based on FFDM, mean overall sensitivity of the students was 29.2% (18.9 - 39.6%). When recombined CEM images were used, mean overall sensitivity of students improved to 82.6% (74.0 - 91.2%) (p=0.001). Mean overall sensitivity of FFDM exams evaluated by radiologists was 75.7% (64.2 - 87.3%), which was lower when compared to student's evaluations on recombined CEM exams, yet not statistically significant (p=0.098). Conclusions: Contrast-enhanced mammography evaluated by non-experienced high school students might improve detection rate of breast cancer when compared to evaluations of only full-field digital mammography by radiologists.