A Population-Based Long-Term Follow-Up of Soft Tissue Angiosarcomas: Characteristics, Treatment Outcomes, and Prognostic Factors.

Angiosarcoma is a rare aggressive and understudied soft tissue sarcoma with pending evidence-based treatment guidelines due to varying study cohorts and inconsistent outcome measures. Surgery with wide resection is currently considered to be the cornerstone in management. In a population-based cohort identified from Danish National Health Registers between 2000 and 2017, this study aimed to define prognostic factors in patients with newly diagnosed soft tissue angiosarcoma. Kaplan-Meier survival analysis demonstrated 5-year overall survival of 28%. Competing risk analysis demonstrated cumulative incidence of local recurrence of 30% and metastasis of 43%. Multivariable Cox models among 154 included patients demonstrated age above 60 years and metastasis to be independently associated with worse overall survival. Cutaneous tumors, surgery, and negative resection margin were independently associated with improved overall survival. Adjuvant oncological treatment did not improve overall survival, risk of metastasis, or recurrence. Negative margin was not associated with lower risk of recurrence and metastasis. We conclude that, despite demonstrated improved survival after surgery with wide resection, overall survival remains poor.

Molecular subtyping improves breast cancer diagnosis in the Copenhagen Breast Cancer Genomics Study.

BACKGROUNDIntrinsic molecular subtypes define distinct biological breast cancers and can be used to further improve diagnosis and risk allocation.METHODSThe Copenhagen Breast Cancer Genomics Study (CBCGS) prospectively included women diagnosed with breast cancer at Rigshospitalet from 2014 to 2021. Eligible patients were females with a primary invasive breast cancer (T1c, if N0M0; otherwise, any T, any N, or any M stage) and no prior malignancy. All patients underwent molecular profiling with the CIT256 and PAM50 molecular profile.RESULTSIn the study period, 2,816 patients were included in the CBCGS. Molecular subtyping showed an increase in nonluminal (molecular-apocrine, luminal C, and Basal-like) as compared with luminal (luminal A, luminal B, and Normal-like) subtypes with increasing stage from I to IV. Across all stages, we found a significant difference in survival among subtypes; 91% of patients with LumA were alive at 5 years compared with 91% for LumB, 84% for LumC, 82% for mApo, and 80% for Basal-like. We identified 442 tumors (16%) that were discordant in subtype between CIT256 and IHC. Discordant subtype proved to be a risk factor of death among patients with IHC luminal breast cancer (hazard ratio [HR], 2.08; 95% CI, 1.51-2.86) in a multivariable Cox regression analysis. Discordance occurred more often among patients with N3, stage IV, or grade III disease.CONCLUSIONOur findings indicate that molecular subtypes are a predominant classification for survival. Assessment is particularly crucial for patients with IHC luminal breast cancer with known high-risk factors, since they are at an increased risk of harboring an aggressive molecular subtype.

Efficacy of mesenchymal stem cell-delivery using perpendicular multi-needle injections to the skin: Evaluation of post-ejection cellular health and dermal delivery.

AIM: Mesenchymal stem cell (MSC)-therapy is increasingly being evaluated in clinical trials. Dermal delivery is not only time consuming but also unreliable, potentially hampering the therapeutic result. Therefore, qualification of cell delivery protocols is essential. This study evaluated a clinically relevant automated multi-needle injection method for cutaneous MSC-therapy, allowing the skin to be readily and timely treated, by assessing both the cellular health post-ejection and dermal delivery. METHODS: Following dispensation through the injector (31 G needles: 9- or 5-pin) the cellular health and potency (perceived- and long-term (12 h) viability, recovery, metabolism, adherence, proliferation and IDO1-expression) of adipose-derived stem cells (10-20-50 ×106 cells/ml) were assessed in vitro in addition to dermal delivery of solution in human skin. RESULTS: No significant detrimental effect on the perceived cell viability, recovery, metabolism, adherence or IDO1-expression of either cell concentration was observed. However, the overall long-term viability and proliferation decreased significantly regardless of cell concentration, nonetheless marginally. An injection depth above 1.0 mm resulted in all needles piercing the skin with dermal delivery from up to 89% needles and minimal reflux to the skin surface, and the results were confirmed by ultrasound and histology. CONCLUSION: The automated injector is capable of delivering dermal cell-doses with an acceptable cell quality.

HLA Class II Histocompatibility Antigen γ Chain (CD74) Expression Is Associated with Immune Cell Infiltration and Favorable Outcome in Breast Cancer.

The triple-negative breast cancer (TNBC) subtype, defined as negative for ER, PgR, and HER2, is biologically more aggressive and with a poorer prognosis than the other subtypes, in part due to the lack of suitable targeted therapies. Consequently, identification of any potential novel therapeutic option, predictive and/or prognostic biomarker, or any other relevant information that may impact the clinical management of this group of patients is valuable. The HLA class II histocompatibility antigen γ chain, or cluster of differentiation 74 (CD74), has been associated with TNBCs, and poorer survival. However, discordant results have been reported for immunohistochemical studies of CD74 expression in breast cancer. Here we report validation studies for use of a novel CD74 antibody, UMAb231. We used this antibody to stain a TMA including 640 human breast cancer samples, and found no association with the TNBC subtype, but did find a positive correlation with outcome. We also found associations between CD74 expression and immune cell infiltration, and expression of programmed death ligand 1 (PD-L1). Given that CD74 may play a role in innate immune system responses and the potential of immunotherapy as a viable treatment strategy for TNBCs, CD74 expression may have predictive value for immune checkpoint therapies.

Functional Proteomic Profiling of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that comprises various disease entities, all of which share a set of common features: a lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, respectively. Because of their receptor status, conventional chemotherapy remains the main therapeutic option for TNBC patients. We employed a reverse phase protein array approach (RPPA), complemented by immunohistochemistry, to quantitatively profile the activation state of 84 actionable key signaling intermediates and phosphoproteins in a set of 44 TNBC samples. We performed supervised and unsupervised approaches to proteomic data analysis to identify groups of samples sharing common characteristics that could be amenable to existing therapies. We found the heterogenous activation of multiple pathways, with PI3 K/AKT/mTOR signaling being the most common event. Some specific individualized therapeutic possibilities include the expression of oncogenic KIT in association with cytokeratin 15 and Erk1/2 positive tumors, both of which may have clinical value.

Prediction of Pathologic Complete Response in Breast Cancer Patients Comparing Magnetic Resonance Imaging with Ultrasound in Neoadjuvant Setting.

BACKGROUND: Some subgroups of breast cancer patients receiving neoadjuvant chemotherapy (NACT) show high rates of pathologic complete response (pCR) in the breast, proposing the possibility of omitting surgery. Prediction of pCR is dependent on accurate imaging methods. This study investigated whether magnetic resonance imaging (MRI) is better than ultrasound (US) in predicting pCR in breast cancer patients receiving NACT. METHODS: This institutional, retrospective study enrolled breast cancer patients receiving NACT who were examined by either MRI or combined US and mammography before surgery from 2016 to 2019. Imaging findings were compared with pathologic response evaluation of the tumor. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for prediction of pCR were calculated and compared between MRI and US. RESULTS: Among 307 patients, 151 were examined by MRI and 156 by US. In the MRI group, 37 patients (24.5 %) had a pCR compared with 51 patients (32.7 %) in the US group. Radiologic complete response (rCR) was found in 35 patients (23.2 %) in the MRI group and 26 patients (16.7 %) in the US group. In the MRI and US groups, estimates were calculated respectively for sensitivity (87.7 % vs 91.4 %), specificity (56.8 % vs 33.3 %), PPV (86.2 % vs 73.8 %), NPV (60.0 % vs 65.4 %), and accuracy (80.1 % vs 72.4 %). CONCLUSIONS: In predicting pCR, MRI was more specific than US, but not sufficiently specific enough to be a valid predictor of pCR for omission of surgery. As an imaging method, MRI should be preferred when future studies investigating prediction of pCR in NACT patients are planned.

Clinical implications of intrinsic molecular subtypes of breast cancer for sentinel node status.

Axillary lymph node status is an important prognostic factor for breast cancer patients and sentinel lymph node biopsy (SLNB) is a less invasive surgical proxy. We examined if consecutively derived molecular subtypes from primary breast cancers provide additional predictive value for SLNB status. 1556 patients with a breast cancer > 10 mm underwent primary surgical procedure including SLNB and tumor specimens were assigned with a transcriptomics-based molecular subtype. 1020 patients had a negative sentinel node (SN) and 536 a positive. A significant association between tumor size and SN status (p < 0.0001) was found across all samples, but no association between size and SN status (p = 0.14) was found for BasL tumors. A BasL subtype was a predictor of an SN-negative status (p = 0.001, OR 0.58, 95% CI 0.38;0.90) and among the BasL, postmenopausal status was a predictor for SN-negative status (p = 0.01). Overall survival was significantly lower (p = 0.02) in patients with BasL tumors and a positive SN. Interestingly, we identified a significant correlation between hormone receptor activity and SN status within the BasL subtype. Taken together, molecular subtypes and hormone receptor activity of breast cancers add predictive value for SLNB status.

Mesenchymal stem cell therapy of acute thermal burns: A systematic review of the effect on inflammation and wound healing.

AIM: Mesenchymal stem cell (MSC) therapies are emerging as a promising strategy to promote tissue repair, and may extend their utility to burn care. This comprehensive review of the extant literature, evaluated all in vivo studies, to elucidate the potential protective and therapeutic effect of MSCs in acute thermal skin burns. METHODS: PubMed was systematically searched, according to PRISMA guidelines, and all relevant preclinical and clinical studies were included according to pre-specified eligibility criteria. RESULTS: Forty-two studies were included in a qualitative synthesis, of which three were human and 39 were animal studies. The preclinical studies showed that MSCs can significantly reduce inflammation, burn wound progression and accelerate healing rate of acute burns. The underlying mechanisms are complex and not fully understood but paracrine modulators, such as immunomodulatory, antioxidative and trophic factors, seem to play important roles. Allogeneic MSC therapy has proved feasible in humans, and could allow for prompt treatment of acute burns in a clinical setting. CONCLUSION: MSC therapy show positive results, regarding improved burn wound healing and immunologic response. However, most findings are based on small animal studies. Randomized clinical trials are warranted to investigate the regenerative effects in human burns before translating the findings into clinical practice.

Cell-Enriched Fat Grafting Improves Graft Retention in a Porcine Model: A Dose-Response Study of Adipose-Derived Stem Cells versus Stromal Vascular Fraction.

BACKGROUND: Cell-enrichment of fat grafts has produced encouraging results, but the optimal concentrations and types of added cells are unknown. The authors investigated the effects of enrichment with various concentrations of ex vivo-expanded adipose-derived stem/stromal cells and stromal vascular fraction on graft retention in a porcine model. METHODS: Adipose-derived stem/stromal cells were culture-expanded, and six fat grafts (30 ml) were prepared for each minipig (n = 13). The authors investigated grafts enriched with 2.5 × 10 to 20 × 10 adipose-derived stem cells/ml and stromal vascular fraction and nonenriched control grafts. Each pig served as its own control. Magnetic resonance imaging was performed immediately after grafting and 120 days postoperatively before the pigs were euthanized, and histologic samples were collected. RESULTS: The authors recorded an enhanced relative graft retention rate of 41 percent in a pool of all cell-enriched grafts compared to the nonenriched control (13.0 percent versus 9.2 percent; p = 0.0045). A comparison of all individual groups showed significantly higher graft retention in the 10 × 10-adipose-derived stem/stromal cells per milliliter group compared with the control group (p = 0.022). No significant differences were observed between the cell-enriched groups (p = 0.66). All fat grafts showed a significantly better resemblance to normal fat tissue in the periphery than in the center (p < 0.009), but no differences in overall graft morphology were observed between groups (p > 0.17). CONCLUSIONS: Cell-enriched fat grafting improved graft retention and was feasible in this porcine model. No significant differences in graft retention were observed among the various adipose-derived stem/stromal cell concentrations or between adipose-derived stem/stromal cell and stromal vascular fraction enrichment. Future studies using this model can help improve understanding of the role of adipose-derived stem/stromal cells in cell-enriched fat grafting.

Phyllodes tumor with a benign heterologous osseous component: a diagnostic challenge.

Phyllodes tumors (PTs) are rare fibroepithelial neoplasms of the breast and constitute 0.3-1% of all primary breast tumors. They should be characterized in to a benign, borderline or malignant category based on a combination of histological features. PTs can show heterologous components, typically sarcomatous, including osteosarcomatous and chondrosarcomatous. Benign heterologous components are exceedingly rare with only one prior reported case in the English literature. This case emphasizes how difficult establishing a correct diagnosis in PTs with heterologous components can be, especially when the tumor consists mainly of a benign heterologous component. We report the case of a 65 year old woman with a recurrent breast tumor initially misdiagnosed as benign osseous metaplasia. The tumor re-occurred as a malignant PT dominated by benign osseous and chondroid metaplasia. Multiple metastases consisting of primarily mature bone and cartilage were seen in the lungs. On microscopic revision and considering the clinical course the primary breast tumor was re-classified as a borderline PT.

A Novel Porcine Model for Future Studies of Cell-enriched Fat Grafting.

BACKGROUND: Cell-enriched fat grafting has shown promising results for improving graft survival, although many questions remain unanswered. A large animal model is crucial for bridging the gap between rodent studies and human trials. We present a step-by-step approach in using the Göttingen minipig as a model for future studies of cell-enriched large volume fat grafting. METHODS: Fat grafting was performed as bolus injections and structural fat grafting. Graft retention was assessed by magnetic resonance imaging after 120 days. The stromal vascular fraction (SVF) was isolated from excised fat and liposuctioned fat from different anatomical sites and analyzed. Porcine adipose-derived stem/stromal cells (ASCs) were cultured in different growth supplements, and population doubling time, maximum cell yield, expression of surface markers, and differentiation potential were investigated. RESULTS: Structural fat grafting in the breast and subcutaneous bolus grafting in the abdomen revealed average graft retention of 53.55% and 15.28%, respectively, which are similar to human reports. Liposuction yielded fewer SVF cells than fat excision, and abdominal fat had the most SVF cells/g fat with SVF yields similar to humans. Additionally, we demonstrated that porcine ASCs can be readily isolated and expanded in culture in allogeneic porcine platelet lysate and fetal bovine serum and that the use of 10% porcine platelet lysate or 20% fetal bovine serum resulted in population doubling time, maximum cell yield, surface marker profile, and trilineage differentiation that were comparable with humans. CONCLUSIONS: The Göttingen minipig is a feasible and cost-effective, large animal model for future translational studies of cell-enriched fat grafting.

Diagnostic challenges in clinical, radiological and histopathological tests regarding papillomatous lesions of the breast.

Papillomas of the female breast is a relatively frequent lesion, and the majority are benign when excised. However, some may host malignant or premalignant areas. Consequently, it is a worldwide accepted principle to excise the lesion whenever diagnosed. However, this leads to a large number of patients having an unnecessary operation. The present study was designed to investigate whether we could find clinical, radiological and pathological factors in the preoperative, diagnostic setting that could identify patients hosting a benign papilloma in order to avoid operation. The patient material consisted of 260 patients, all with a preoperative diagnosis of a papillomatous process in core biopsy. The lesion was excised, and 71% had a benign lesion. The rest had lesions ranging from premalignant to malignant. In the clinical, radiological and histopathological investigations conducted, we were not able to identify factors that statistically significant could predict whether the lesion was benign or malignant. However, our data showed a higher prevalence of malignant and premalignant lesions for older patient, larger lesions, and lesions found at a longer distance from the papilla. We conclude that, since almost 30% of the patients in our study ended up with a premalignant or malignant diagnosis, where no statistically significant preoperative factors could indicate a benign outcome, operation is warranted in all patients with a preoperative diagnosis of a papillomatous lesion.

PAM50 Risk of Recurrence Score Predicts 10-Year Distant Recurrence in a Comprehensive Danish Cohort of Postmenopausal Women Allocated to 5 Years of Endocrine Therapy for Hormone Receptor-Positive Early Breast Cancer.

Purpose The PAM50-based Prosigna risk of recurrence (ROR) score has been validated in randomized clinical trials to predict 10-year distant recurrence (DR). The value of Prosigna for predicting DR was examined in a comprehensive nationwide Danish cohort consisting of postmenopausal women with hormone receptor-positive early breast cancer treated with 5 years of endocrine therapy alone. Patients and Methods Using the population-based Danish Breast Cancer Cooperative Group database, follow-up data were collected on all patients diagnosed from 2000 through 2003 who, by nationwide guidelines, were treated with endocrine therapy for 5 years. Primary tumor blocks from 2,740 patients were tested with Prosigna and, after determination of human epidermal growth factor receptor 2 (HER2) status, data from 2,558 hormone receptor-positive/HER2-negative samples were analyzed, including 1,395 node-positive patients. Fine and Gray models were applied to determine the prognostic value of ROR for DR. Results Median follow-up for recurrence was 9.2 years. Twenty-six percent of the node-positive patients were classified as low ROR (n = 359) with a DR risk of 3.5% (95% confidence interval [CI], 1.9% to 6.1%) versus a DR risk of 22.1% (95% CI, 18.6% to 25.8%) at 10 years for patients classified as high ROR (n = 648). Node-negative patients classified as low and high ROR had a risk of DR of 5.0% (95% CI, 2.9% to 8.0%) and 17.8% (95% CI, 14.0% to 22.0%), respectively. Luminal B tumors (n = 947; DR risk, 18.4% [95% CI: 15.7% to 21.3%]) had a significantly worse outcome than luminal A tumors (n = 1,474,;DR risk, 7.6% [95% CI: 6.1% to 9.2%]; P < .001). Conclusion Prosigna ROR score improved the prediction of outcome in this nationwide Danish population. In a real-world setting, Prosigna can reliably identify node-negative patients and a significant proportion of patients with one to three positive nodes who can be spared treatment with adjuvant chemotherapy.

Characterization of basal-like subtype in a Danish consecutive primary breast cancer cohort.

BACKGROUND: Transcriptome analysis enables classification of breast tumors into molecular subtypes. BRCA1/2 predisposed patients are more likely to suffer from a basal-like subtype and this group of patients displays a more distinct phenotype and genotype. Hence, in-depth characterization of this separate entity is needed. MATERIAL AND METHODS: Molecular subtyping was performed on a consecutive and unselected series of 1560 tumors from patients with primary breast cancer. Tumors were classified by the 256 gene expression signature (CIT) and associated with basic clinical characteristics and aggregated expression levels in the hallmark gene sets. RESULTS: Of the 1560 samples, 168 were classified basal-like and 120 patients were screened for BRCA1/2 mutations, resulting in 19 BRCA1/2 carriers, 95 non-carriers and six patients carried variants of unknown significance. The BRCA1/2 carriers were significantly younger and there were no carriers above 60 years of age. The tumors showed a loss in DNA-repair profile, as well as an upregulation in proliferative cancer signaling pathways. A robust molecular signature for identification of the BRCA1/2 - carriers was infeasible in the current cohort. Patients with a basal like breast cancer had the lowest median age and the largest median tumor size. They were almost exclusively diagnosed in disease stage III. CONCLUSIONS: Basal-like subtype is indeed a separate entity compared with other molecular breast cancer subtypes and the clinical course for this patient group should reflect the aggressiveness of this cancer. Taken together, patients being diagnosed with a basal-like breast cancer are in the youngest segment of breast cancer patients and are mainly diagnosed in stage III disease.

Molecular subtyping of breast cancer improves identification of both high and low risk patients.

BACKGROUND: Transcriptome analysis enables classification of breast tumors into molecular subtypes that correlate with prognosis and effect of therapy. We evaluated the clinical benefits of molecular subtyping compared to our current diagnostic practice. MATERIALS AND METHODS: Molecular subtyping was performed on a consecutive and unselected series of 524 tumors from women with primary breast cancer (n = 508). Tumors were classified by the 256 gene expression signature (CIT) and compared to conventional immunohistochemistry (IHC) procedures. RESULTS: More than 99% of tumors were eligible for molecular classification and final reports were available prior to the multidisciplinary conference. Using a prognostic standard mortality rate index (PSMRi) developed by the Danish Breast Cancer Group (DBCG) 39 patients were assigned with an intermediate risk and among these 16 (41%) were furthermore diagnosed by the multi-gene signature assigned with a luminal A tumor and consequently spared adjuvant chemotherapy. There was overall agreement between mRNA derived and IHC hormone receptor status, whereas IHC Ki67 protein proliferative index proved inaccurate, compared to the mRNA derived index. Forty-one patients with basal-like (basL) subtypes were screened for predisposing mutations regardless of clinical predisposition. Of those 17% carried pathogenic mutations. CONCLUSION: Transcriptome based subtyping of breast tumors evidently reduces the need for adjuvant chemotherapy and improves identification of women with predisposing mutations. The results imply that transcriptome profiling should become an integrated part of current breast cancer management.

An inter-observer Ki67 reproducibility study applying two different assessment methods: on behalf of the Danish Scientific Committee of Pathology, Danish breast cancer cooperative group (DBCG).

INTRODUCTION: In 2011, the St. Gallen Consensus Conference introduced the use of pathology to define the intrinsic breast cancer subtypes by application of immunohistochemical (IHC) surrogate markers ER, PR, HER2 and Ki67 with a specified Ki67 cutoff (>14%) for luminal B-like definition. Reports concerning impaired reproducibility of Ki67 estimation and threshold inconsistency led to the initiation of this quality assurance study (2013-2015). The aim of the study was to investigate inter-observer variation for Ki67 estimation in malignant breast tumors by two different quantification methods (assessment method and count method) including measure of agreement between methods. MATERIAL AND METHODS: Fourteen experienced breast pathologists from 12 pathology departments evaluated 118 slides from a consecutive series of malignant breast tumors. The staining interpretation was performed according to both the Danish and Swedish guidelines. Reproducibility was quantified by intra-class correlation coefficient (ICC) and Lights Kappa with dichotomization of observations at the larger than (>) 20% threshold. The agreement between observations by the two quantification methods was evaluated by Bland-Altman plot. RESULTS: For the fourteen raters the median ranged from 20% to 40% by the assessment method and from 22.5% to 36.5% by the count method. Light's Kappa was 0.664 for observation by the assessment method and 0.649 by the count method. The ICC was 0.82 (95% CI: 0.77-0.86) by the assessment method vs. 0.84 (95% CI: 0.80-0.87) by the count method. CONCLUSION: Although the study in general showed a moderate to good inter-observer agreement according to both ICC and Lights Kappa, still major discrepancies were identified in especially the mid-range of observations. Consequently, for now Ki67 estimation is not implemented in the DBCG treatment algorithm.

Standardized assessment of tumor-infiltrating lymphocytes in breast cancer: an evaluation of inter-observer agreement between pathologists.

INTRODUCTION: In breast cancer, there is a growing body of evidence that tumor-infiltrating lymphocytes (TILs) may have clinical utility and may be able to direct clinical decisions for subgroups of patients. Clinical utility is, however, not sufficient for warranting the implementation of a new biomarker in the routine practice, and evaluation of the analytical validity is needed, including testing the reproducibility of decentralized assessment of TILs. The aim of this study was to evaluate the inter-observer agreement of TILs assessment using a standardized method, as proposed by the International TILs Working Group 2014, applied to a cohort of breast cancers reflecting an average breast cancer population. MATERIAL AND METHODS: Stromal TILs were assessed using full slide sections from 124 breast cancers with varying histology, malignancy grade and ER- and HER2 status. TILs were estimated by nine dedicated breast pathologists using scanned hematoxylin-eosin stainings. TILs results were categorized using various cutoffs, and the inter-observer agreement was evaluated using the intraclass coefficient (ICC), Kappa statistics as well as individual overall agreements with the median value of TILs. RESULTS: Evaluation of TILs led to an ICC of 0.71 (95% CI: 0.65-0.77) corresponding to an acceptable agreement. Kappa values were in the range of 0.38-0.46 corresponding to a fair to moderate agreement. The individual agreements increased, when using only two categories ('high' vs. 'low' TILs) and a cutoff of 50-60%. DISCUSSION: The results of the present study are in accordance with previous studies, and shows that the proposed methodology for standardized evaluation of TILs renders an acceptable inter-observer agreement. The findings, however, indicate that assessment of TILs needs further refinement, and is in support of the latest St. Gallen Consensus, that routine reporting of TILs for early breast cancer is not ready for implementation in a clinical setting.

Strain histograms are equal to strain ratios in predicting malignancy in breast tumours.

OBJECTIVES: To assess whether strain histograms are equal to strain ratios in predicting breast tumour malignancy and to see if either could be used to upgrade Breast Imaging Reporting and Data System (BI-RADS) 3 tumours for immediate biopsy. METHODS: Ninety-nine breast tumours were examined using B-mode BI-RADS scorings and strain elastography. Strain histograms and ratios were assessed, and areas- under-the-receiver-operating-characteristic-curve (AUROC) for each method calculated. In BI-RADS 3 tumours cut-offs for strain histogram and ratio values were calculated to see if some tumours could be upgraded for immediate biopsy. Linear regression was performed to evaluate the effect of tumour depth and size, and breast density on strain elastography. RESULTS: Forty-four of 99 (44.4%) tumours were malignant. AUROC of BI-RADS, strain histograms and strain ratios were 0.949, 0.830 and 0.794 respectively. There was no significant difference between AUROCs of strain histograms and strain ratios (P = 0.405), while they were both inferior to BI-RADS scoring (P<0.001, P = 0.008). Four out of 26 BI-RADS 3 tumours were malignant. When cut-offs of 189 for strain histograms and 1.44 for strain ratios were used to upgrade BI-RADS 3 tumours, AUROCS were 0.961 (Strain histograms and BI-RADS) and 0.941 (Strain ratios and BI-RADS). None of them was significantly different from BI-RADS scoring alone (P = 0.249 and P = 0.414). Tumour size and depth, and breast density influenced neither strain histograms (P = 0.196, P = 0.115 and P = 0.321) nor strain ratios (P = 0.411, P = 0.596 and P = 0.321). CONCLUSION: Strain histogram analyses are reliable and easy to do in breast cancer diagnosis and perform comparably to strain ratio analyses. No significant difference in AUROCs between BI-RADS scoring and elastography combined with BI-RADS scoring was found in this study.