Experiencias antes y después de la mamoplastia de reducción en pacientes con macromastia / Experiences before and after reduction mammoplasty in patients with macromastia

Introducción: la hipertrofia mamaria o macromastia es un desarrollo excesivo y desproporcionado de tejido mamario, que suele ir asociada con síntomas físicos y psíquicos que alteran la calidad de vida y pueden ser en ocasiones tremendamente incapacitantes. Prácticamente la única opción terapéutica para estas pacientes es la mamoplastia de reducción, procedimiento quirúrgico que ha demostrado ser muy eficaz para reducir los síntomas. Objetivo: describir y analizar los resultados de la intervención desde el punto de vista de las propias pacientes con macromastia antes y después de la reducción mamaria, a través de los comentarios expresados por ellas mismas. Material y métodos: Estudio prospectivo. Análisis de las características de las pacientes, valoración del cambio en la salud experimentado tras la intervención y las experiencias subjetivas de las mujeres relativas a su macromastia antes y después de la intervención. Resultados: Un total de 121 mujeres intervenidas de macromastia con una edad media de 40,71 años participaron en el estudio. Las pacientes experimentaron un cambio positivo en su estado de salud tras la intervención (p < 0,001). La mayoría de los problemas verbalizados hacían referencia a la dificultad en el vestir y en realizar actividad física, así como la gran mejoría experimentada tras la intervención Conclusión: las experiencias compartidas por las mujeres con macromastia tras la reducción mamaria evidencian una significativa mejoría tanto en su percepción de la salud como en su vida cotidiana, incluyendo el encontrar una ropa adecuada a su gusto y necesidades de actividad física. (AU)

Introduction: Mammary hypertrophy or macromastia is an excessive and disproportionate development of breast tissue, which is usually associated with physical and mental symptoms that alter the quality of life and can sometimes be tremendously disabling. Practically the only therapeutic option for these patients is a reduction mammoplasty, a surgical procedure that has proven to be very effective in reducing symptoms. Objective: To describe and analyze the outcomes of the intervention from the point of view of the patients themselves through the comments expressed by patients with macromastia before and after breast reduction. Material and methods: Prospective study. Analysis of the characteristics of the patients, assessment of the health change experienced after the intervention, and the subjective experiences of the women regarding their macromastia before and after the intervention. Results: A total of 121 women operated on for macromastia with a mean age of 40.71 years participated in the study. The patients experienced a positive change in their health status after the intervention (p < 0.001). Most of the verbalized problems referred to the difficulty in dressing and carrying out physical activity, as well as the great improvement experienced after the intervention. Conclusion: The experiences shared by women with macromastia after breast reduction surgery demonstrate a significant improvement not only in their perception of health but also in their daily life, including finding clothing that is suitable for their preferences and physical activity needs. (AU)

Clinical, histological features, and predictors of relapse in patients with idiopathic granulomatous mastitis.

Idiopathic granulomatous mastitis is a benign, inflammatory disease of breasts characterized by non-caseating granulomas. Our study aims to identify distinguishing clinical and histopathological features of relapsing disease compared to those in complete remission. We queried databases at our institution (1990-2021) to include females ≥18 years with biopsy-proven diagnosis of idiopathic granulomatous mastitis, excluding patients with breast cancer, lymphoproliferative disorders, solid organ malignancy, foreign body reaction in breast, plasma cell mastitis, and ductal ectasia. Remission was defined as a 3-month period without recurrence of symptoms or imaging findings. Relapse was defined as recurrence after 3 months of remission. Clinical and histopathological features were compared using 2-sample t tests and chi-squared tests. Of the 27 patients that met our inclusion criteria, the mean age at diagnosis was 35.8 years (± standard deviation 9.4 years) with a mean body mass index of 31.7 kg/m2 (± standard deviation 6.7 kg/m2). 11 (41%) were Hispanic, 25 (93%) had at least one previous full-term pregnancy prior to diagnosis and 8 (30%) were on oral contraceptives. Remission was seen in 18 patients (66%) and 9 (33%) had relapse. Six of these patients received steroids after antibiotics, while 5 patients received methotrexate. Three (33%) patients with relapse and 14 (77%) with remission, had abscess formation confirmed on histopathology (P = .04). Patients with remission had a higher number of abscesses on histopathology and history of oral contraceptive use was associated with more relapse. By identifying key clinical and histopathological findings in this population may guide prognosis and treatment of these patients.

Added value of clinical decision rules for the management of enhancing breast MRI lesions: A systematic comparison of the Kaiser score and the Göttingen score.

PURPOSE: We investigated the added value of two internationally used clinical decision rules in the management of enhancing lesions on breast MRI. METHODS: This retrospective, institutional review board approved study included consecutive patients from two different populations. Patients received breast MRI according to the recommendations of the European Society of Breast Imaging (EUSOBI). Initially, all examinations were assessed by expert readers without using clinical decision rules. All lesions rated as category 4 or 5 according to the Breast Imaging Reporting and Data System were histologically confirmed. These lesions were re-evaluated by an expert reader blinded to the histology. He assigned each lesion a Göttingen score (GS) and a Kaiser score (KS) on different occasions. To provide an estimate on inter-reader agreement, a second fellowship-trained reader assessed a subset of these lesions. Subgroup analyses based on lesion type (mass vs. non-mass), size (>1 cm vs. ≤ 1 cm), menopausal status, and significant background parenchymal enhancement were conducted. The areas under the ROC curves (AUCs) for the GS and KS were compared, and the potential to avoid unnecessary biopsies was determined according to previously established cutoffs (KS > 4, GS > 3) RESULTS: 527 lesions in 506 patients were included (mean age: 51.8 years, inter-quartile-range: 43.0-61.0 years). 131/527 lesions were malignant (24.9 %; 95 %-confidence-interval: 21.3-28.8). In all subgroups, the AUCs of the KS (median = 0.91) were higher than those of the GS (median = 0.83). Except for "premenopausal patients" (p = 0.057), these differences were statistically significant (p ≤ 0.01). Kappa agreement was higher for the KS (0.922) than for the GS (0.358). CONCLUSION: Both the KS and the GS provided added value for the management of enhancing lesions on breast MRI. The KS was superior to the GS in terms of avoiding unnecessary biopsies and showed superior inter-reader agreement; therefore, it may be regarded as the clinical decision rule of choice.

Breast Cancer Prognosis: A Study on Mortality Indicators.

Background: The prognosis of breast cancer patients is critical for tailored treatment options. While previous observational studies have identified various prognostic markers, a consensus in their clinical application is lacking. This single-center retrospective study aimed to validate the most frequent risk factors associated with increased mortality in breast cancer patients. Methods: Our study spanned an 8-year interval (2014-2020) and included 213 female patients with stage IIA-IIIB breast cancer. Key variables such as age, disease stage, and type of treatment were analyzed in relation to one-year survival as the primary outcome measure. Results: Elevated preoperative levels of tumor markers ACE and CA 15-3, larger tumor size, and advanced lymph nodal invasion were significantly associated with increased mortality. Immunohistochemistry indicated that the presence of Estrogen and Progesterone Receptors (ER and PR) were protective factors, whereas Human Epidermal Growth Factor Receptor 2 (HER2) was a negative prognostic indicator. Among molecular subtypes, Luminal A demonstrated protective effects, whereas HER2-positive and Triple-negative subtypes were identified as risk factors. Conclusion: This study confirms the significant role of tumor size, lymph node stage, and specific molecular markers in predicting breast cancer mortality. These findings contribute to a nuanced understanding of disease prognosis and offer crucial insights for clinicians in managing treatment plans.

Saliency of breast lesions in breast cancer detection using artificial intelligence.

The analysis of mammograms using artificial intelligence (AI) has shown great potential for assisting breast cancer screening. We use saliency maps to study the role of breast lesions in the decision-making process of AI systems for breast cancer detection in screening mammograms. We retrospectively collected mammograms from 191 women with screen-detected breast cancer and 191 healthy controls matched by age and mammographic system. Two radiologists manually segmented the breast lesions in the mammograms from CC and MLO views. We estimated the detection performance of four deep learning-based AI systems using the area under the ROC curve (AUC) with a 95% confidence interval (CI). We used automatic thresholding on saliency maps from the AI systems to identify the areas of interest on the mammograms. Finally, we measured the overlap between these areas of interest and the segmented breast lesions using Dice's similarity coefficient (DSC). The detection performance of the AI systems ranged from low to moderate (AUCs from 0.525 to 0.694). The overlap between the areas of interest and the breast lesions was low for all the studied methods (median DSC from 4.2% to 38.0%). The AI system with the highest cancer detection performance (AUC = 0.694, CI 0.662-0.726) showed the lowest overlap (DSC = 4.2%) with breast lesions. The areas of interest found by saliency analysis of the AI systems showed poor overlap with breast lesions. These results suggest that AI systems with the highest performance do not solely rely on localized breast lesions for their decision-making in cancer detection; rather, they incorporate information from large image regions. This work contributes to the understanding of the role of breast lesions in cancer detection using AI.

The "teacup sign": Significance in breast imaging.

Milk of calcium (MOC) is a term used for sedimented calcifications within small cysts (Milk of Calcium - an overview|ScienceDirect Topics, n.d.). MOC in the breast is a benign entity and present in 4-6% of women that undergo diagnostic mammography (Park et al., 2008).2 Calcium particles within cysts produce 'teacup'-shaped calcifications on true lateral views, and smudged calcifications on craniocaudal (CC) views (Veloso Gomes et al., n.d.).3 On the CC projection, the calcifications will have a cloudlike or smudgy appearance like tea leaves in the bottom of a teacup (Milk of Calcium - an overview|ScienceDirect Topics, n.d.). Because this is a characteristic benign finding, there is no need for the patient to undergo a biopsy.

Subcategorization of suspicious non-mass-like enhancement lesions(BI-RADS-MRI Category4).

BACKGROUND: This study aims to providing a reliable method that has good compliance and is easy to master to improve the accuracy of NMLE diagnosis. METHODS: This study retrospectively analyzed 122 cases of breast non-mass-like enhancement (NMLE) lesions confirmed by postoperative histology. MRI features and clinical features of benign and malignant non-mass enhancement breast lesions were compared by using independent sample t test, χ2test and Fisher exact test. P < 0.05 was considered statistically significant. Statistically significant parameters were then included in logistic regression analysis to build a multiparameter differential diagnosis modelto subdivide the BI-RADS Category 4. RESULTS: The distribution (odds ratio (OR) = 8.70), internal enhancement pattern (OR = 6.29), ADC value (OR = 5.56), and vascular sign (OR = 2.84) of the lesions were closely related to the benignity and malignancy of the lesions. These signs were used to build the MRI multiparameter model for differentiating benign and malignant non-mass enhancement breast lesions. ROC analysis revealed that its optimal diagnostic cut-off value was 5. The diagnostic specificity and sensitivity were 87.01% and 82.22%, respectively. Lesions with 1-6 points were considered BI-RADS category 4 lesions, and the positive predictive values of subtypes 4a, 4b, and 4c lesions were15.79%, 31.25%, and 77.78%, respectively. CONCLUSIONS: Comprehensively analyzing the features of MRI of non-mass enhancement breast lesions and building the multiparameter differential diagnosis model could improve the differential diagnostic performance of benign and malignant lesions.

Evaluating the effectiveness of stain normalization techniques in automated grading of invasive ductal carcinoma histopathological images.

Debates persist regarding the impact of Stain Normalization (SN) on recent breast cancer histopathological studies. While some studies propose no influence on classification outcomes, others argue for improvement. This study aims to assess the efficacy of SN in breast cancer histopathological classification, specifically focusing on Invasive Ductal Carcinoma (IDC) grading using Convolutional Neural Networks (CNNs). The null hypothesis asserts that SN has no effect on the accuracy of CNN-based IDC grading, while the alternative hypothesis suggests the contrary. We evaluated six SN techniques, with five templates selected as target images for the conventional SN techniques. We also utilized seven ImageNet pre-trained CNNs for IDC grading. The performance of models trained with and without SN was compared to discern the influence of SN on classification outcomes. The analysis unveiled a p-value of 0.11, indicating no statistically significant difference in Balanced Accuracy Scores between models trained with StainGAN-normalized images, achieving a score of 0.9196 (the best-performing SN technique), and models trained with non-normalized images, which scored 0.9308. As a result, we did not reject the null hypothesis, indicating that we found no evidence to support a significant discrepancy in effectiveness between stain-normalized and non-normalized datasets for IDC grading tasks. This study demonstrates that SN has a limited impact on IDC grading, challenging the assumption of performance enhancement through SN.

Crosstalk and plasticity driving between cancer-associated fibroblasts and tumor microenvironment: significance of breast cancer metastasis.

Cancer-associated fibroblasts (CAFs) are the most abundant stromal cell population in breast tumors. A functionally diverse population of CAFs increases the dynamic complexity of the tumor microenvironment (TME). The intertwined network of the TME facilitates the interaction between activated CAFs and breast cancer cells, which can lead to the proliferation and invasion of breast cells. Considering the special transmission function of CAFs, the aim of this review is to summarize and highlight the crosstalk between CAFs and breast cancer cells in the TME as well as the relationship between CAFs and extracellular matrix (ECM), soluble cytokines, and other stromal cells in the metastatic state. The crosstalk between cancer-associated fibroblasts and tumor microenvironment also provides a plastic therapeutic target for breast cancer metastasis. In the course of the study, the inhibitory effects of different natural compounds on targeting CAFs and the advantages of different drug combinations were summarized. CAFs are also widely used in the diagnosis and treatment of breast cancer. The cumulative research on this phenomenon supports the establishment of a targeted immune microenvironment as a possible breakthrough in the prevention of invasive metastasis of breast cancer.

Breast carcinoma grading on core needle biopsy - to grade or not to grade?

Core needle biopsy (CNB) is well established as an important diagnostic tool in diagnosing breast cancer and it is now considered the initial method of choice for diagnosing breast disease and the basis for the treatment planning. The concordance rate between CNB and surgical excision specimen in determination of histological grade (HG) varies widely across literature, ranging from 59-91%. The aim of our study was to investigate the level of concordance between CNB and surgical excision specimen for the determination of HG for breast cancer patients. The study population included 157 women with a breast tumor who underwent a core needle biopsy for breast carcinoma and a subsequent surgical excision of the tumor. The concordance level between core needle biopsy and surgical resection specimen for overall histologic grading was 73%: for tubule formation - 71%, for nuclear pleomorphism - 91%, for the mitotic index - 59%. Our study shows that our institution's histologic grading of CNBs and surgical excisions shows a fairly good correlation and is useful for the planning of treatment.

3-D chromatin conformation, accessibility, and gene expression profiling of triple-negative breast cancer.

OBJECTIVES: Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with limited treatment options. Unlike other breast cancer subtypes, the scarcity of specific therapies and greater frequencies of distant metastases contribute to its aggressiveness. We aimed to find epigenetic changes that aid in the understanding of the dissemination process of these cancers. DATA DESCRIPTION: Using CRISPR/Cas9, our experimental approach led us to identify and disrupt an insulator element, IE8, whose activity seemed relevant for cell invasion. The experiments were performed in two well-established TNBC cellular models, the MDA-MB-231 and the MDA-MB-436. To gain insights into the underlying molecular mechanisms of TNBC invasion ability, we generated and characterized high-resolution chromatin interaction (Hi-C) and chromatin accessibility (ATAC-seq) maps in both cell models and complemented these datasets with gene expression profiling (RNA-seq) in MDA-MB-231, the cell line that showed more significant changes in chromatin accessibility. Altogether, our data provide a comprehensive resource for understanding the spatial organization of the genome in TNBC cells, which may contribute to accelerating the discovery of TNBC-specific alterations triggering advances for this devastating disease.

Diagnostic value of digital breast tomosynthesis and synthetic images in patients with breast cancer.

Background: Different imaging techniques are used in the diagnosis of breast cancer. The low sensitivity of mammography to detect cancer in the dense breast parenchyma and the lack of standard application of digital breast tomosynthesis (DBT) are some of the problems. Therefore, breast cancer imaging techniques should be compared in terms of conspicuity and characterization of lesions. Aim: Full-field digital mammography (DM) and synthetic mammography (SM) which are obtained from the slices of digital breast tomosynthesis (DBT) give similar results in terms of conspicuity and characterization of the lesions in detecting breast cancer. Patients and Methods: In this retrospective study, 47 women diagnosed with breast cancer were included in the study. DM, SM, and DBT images were evaluated by scoring the conspicuity of the index lesion in the parenchyma and its characterization in terms of contour and shape with a 4-point scale. In addition, the conspicuity of the lesions in relation to lesion size and breast density was examined with these three techniques. Results: There is no significant difference between DM and SM techniques for index lesion conspicuity and characterization; however, the imaging score of DBT is significantly higher than other techniques for the conspicuity and characterization of the lesions. In terms of the conspicuity of the lesions in relation to lesion size, DM and SM techniques show significant difference according to the size of the lesion, whereas the DBT technique did not show significant difference. While mammography type is a determinant of lesion conspicuity in only DM and SM techniques, conspicuity findings do not differ significantly in the DBT technique. Conclusion: In conclusion, it was shown that standard images and SM images obtained from DBT did not differ significantly in terms of conspicuity and characterization of lesions. Thus, DBT is significantly superior to the DM and SM images. While the DM and SM images are more successful in showing large lesions and lesion detection in nondense breasts, DBT images were not affected by lesion size and breast density.

CAPNet: Context attention pyramid network for computer-aided detection of microcalcification clusters in digital breast tomosynthesis.

BACKGROUND AND OBJECTIVE: Computer-aided detection (CADe) of microcalcification clusters (MCs) in digital breast tomosynthesis (DBT) is crucial in the early diagnosis of breast cancer. Although convolutional neural network (CNN)-based detection models have achieved excellent performance in medical lesion detection, they are subject to some limitations in MC detection: 1) Most existing models employ the feature pyramid network (FPN) for multi-scale object detection; however, the rough feature sharing between adjacent layers in the FPN may limit the detection ability for small and low-contrast MCs; and 2) the MCs region only accounts for a small part of the annotation box, so the features extracted indiscriminately within the whole box may easily be affected by the background. In this paper, we develop a novel CNN-based CADe method to alleviate the impacts of the above limitations for the accurate and rapid detection of MCs in DBT. METHODS: The proposed method has two parts: a novel context attention pyramid network (CAPNet) for intra-layer MC detection in two-dimensional (2D) slices and a three-dimensional (3D) aggregation procedure for aggregating 2D intra-layer MCs into a 3D result according to their connectivity in 3D space. The proposed CAPNet is based on an anchor-free and one-stage detection architecture and contains a context feature selection fusion (CFSF) module and a microcalcification response (MCR) branch. The CFSF module can efficiently enrich shallow layers' features by the complementary selection of local context features, aiming to reduce the missed detection of small and low-contrast MCs. The MCR branch is a one-layer branch parallel to the classification branch, which can alleviate the influence of the background region within the annotation box on feature extraction and enhance the ability of the model to distinguish MCs from normal breast tissue. RESULTS: We performed a comparison experiment on an in-house clinical dataset with 648 DBT volumes, and the proposed method achieved impressive performance with a sensitivity of 91.56 % at 1 false positive per DBT volume (FPs/volume) and 93.51 % at 2 FPs/volume, outperforming other representative detection models. CONCLUSIONS: The experimental results indicate that the proposed method is effective in the detection of MCs in DBT. This method can provide objective, accurate, and quick diagnostic suggestions for radiologists, presenting potential clinical value for early breast cancer screening.

Evaluation of the association of area-level socioeconomic deprivation and breast cancer recurrence by oestrogen receptor subtypes in Scotland.

BACKGROUND: Women from socioeconomically deprived areas have lower breast cancer (BC) incidence rates for screen-detected oestrogen receptor (ER) + tumours and higher mortality for select tumour subtypes. We aimed to determine if ipsilateral breast cancer recurrence (IBR) differs by Scottish Index of Multiple Deprivation (SIMD) quintile and tumour subtype in Scotland. METHODS: Patient data for primary invasive BC diagnosed in 2007-2008 in Scotland was analysed. Manual case-note review for 3495 patients from 10 years post-diagnosis was used. To determine the probability of IBR while accounting for the competing risk of death from any cause, cumulative incidence functions stratified by ER subtype and surgery were plotted. Multivariable Cox Proportional Hazards models were used to estimate the association of SIMD accounting for other predictors of IBR. RESULTS: Among 2819 ER + tumours, 423 patients had a recurrence and 438 died. SIMD was related to death (p = 0.018) with the most deprived more likely to have died in the 10-year period (17.7% vs. 12.9%). We found no significant differences by SIMD in prognostic tumour characteristics (grade, TNM stage, treatment, screen-detection) or risk of IBR. Among 676 patients diagnosed with ER- tumours, 105 died and 185 had a recurrence. We found no significant differences in prognostic tumour characteristics by SIMD except screen detection with the most deprived more likely than the least to have their tumours detected from screening (46.9% vs. 28%, p = 0.03). Among patients with ER- tumours, 50% had mastectomy and the most deprived had increased 5-year IBR risk compared to the least deprived (HR 3.03 [1.41-6.53]). CONCLUSIONS: IBR is not a major contributor to mortality differences by SIMD for the majority of BC patients in our study. The lack of inequities in IBR are likely due to standardised treatment protocols and access to healthcare. The association with socioeconomic deprivation and recurrence for ER- tumours requires further study.

Pathology of MRI and second-look ultrasound detected multifocal breast cancer.

INTRODUCTION: Targeted second-look ultrasound (US) is often performed following MRI of the breast to determine if an MRI-detected lesion is visible on US and thus amenable to US-guided biopsy. This study aimed to assess the pathology of lesions detected and biopsied on the second-look US. In particular, for multifocal cancers, whether the pathology of additional lesions detected by second-look US is different to the index lesion. METHODS: Multicentre single-institution retrospective study of 300 consecutive cases of second-look US biopsies from August 2017 to April 2022 was performed, with their histopathology and imaging characteristics recorded. For multifocal cancers, Wilcoxon Signed Ranks Tests were used to compare differences between the index and additional lesions in the histopathology category (i.e., high-risk benign, precursor or malignant) and BRE grade. RESULTS: 69 multifocal cancers were detected. For the purposes of this study, additional lesions were considered more invasive if they were of a higher histopathological category or BRE grade, or demonstrated lymphovascular invasion when the primary lesion did not. 15/69 additional lesions were not seen on the initial mammogram/tomography or ultrasound, seen on subsequent MRI and second look US, and were less invasive than the index lesion. 3/69 additional lesions were more invasive than their index lesions. Wilcoxon Signed Ranks test showed additional lesions were of either similar or lesser invasiveness compared to index lesions (z= -3.207, p = 0.001) in the histopathological category, and the same or lower BRE grade (z= -2.972, p = 0.003). CONCLUSION: In multifocal breast cancers, additional lesions detected on MRI and second-look US have the same or less invasive histopathology compared to the index lesion.

Synthetic MRI in breast cancer: differentiating benign from malignant lesions and predicting immunohistochemical expression status.

To evaluate and compare the performance of synthetic magnetic resonance imaging (SyMRI) in classifying benign and malignant breast lesions and predicting the expression status of immunohistochemistry (IHC) markers. We retrospectively analysed 121 patients with breast lesions who underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and SyMRI before surgery in our hospital. DCE-MRI was used to assess the lesions, and then regions of interest (ROIs) were outlined on SyMRI (before and after enhancement), and apparent diffusion coefficient (ADC) maps to obtain quantitative values. After being grouped according to benign and malignant status, the malignant lesions were divided into high and low expression groups according to the expression status of IHC markers. Logistic regression was used to analyse the differences in independent variables between groups. The performance of the modalities in classification and prediction was evaluated by receiver operating characteristic (ROC) curves. In total, 57 of 121 lesions were benign, the other 64 were malignant, and 56 malignant lesions performed immunohistochemical staining. Quantitative values from proton density-weighted imaging prior to an injection of the contrast agent (PD-Pre) and T2-weighted imaging (T2WI) after the injection (T2-Gd), as well as its standard deviation (SD of T2-Gd), were valuable SyMRI parameters for the classification of benign and malignant breast lesions, but the performance of SyMRI (area under the curve, AUC = 0.716) was not as good as that of ADC values (AUC = 0.853). However, ADC values could not predict the expression status of breast cancer markers, for which SyMRI had excellent performance. The AUCs of androgen receptor (AR), estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), p53 and Ki-67 were 0.687, 0.890, 0.852, 0.746, 0.813 and 0.774, respectively. SyMRI had certain value in distinguishing between benign and malignant breast lesions, and ADC values were still the ideal method. However, to predict the expression status of IHC markers, SyMRI had an incomparable value compared with ADC values.

Overexpression of TPL2 may be a predictor of good prognosis in patients with breast invasive ductal carcinoma.

The objective of this study was to investigate the clinical significance and roles of tumor progression locus 2 (TPL2) and peptidyl-prolyl cis-trans isomerase 1 (Pin1) in the occurrence and development of breast invasive ductal carcinoma (IDC). Immunohistochemistry was used to detect the expression of TPL2 and Pin1 in human breast tissues, which included normal breast tissues (Normal), tissues with fibrocystic changes (FCC), ductal carcinoma in situ (DCIS), and IDC. The roles of TPL2 and Pin1 in the occurrence and development of IDC, as well as the correlation between their expression levels and clinicopathological parameters, were analyzed. Compared with Normal and FCC groups, the overexpression of TPL2 and Pin1 was significantly increased in DCIS and IDC groups (DCIS vs Normal: P = 0.002/P < 0.001; IDC vs Normal: P = 0.007/P = 0.003; DCIS vs. FCC: P = 0.008/P = 0.004; IDC vs. FCC: P = 0.04/P = 0.043). The expression levels of TPL2 and Pin1 were positively correlated in DCIS and IDC groups (P = 0.001, P = 0.011). In the IDC group, the Ki67 level in the TPL2 overexpression group was significantly lower than that in the TPL2 low expression group (P = 0.02). The TPL2 overexpression rate was significantly higher in IDC with histological grades 1-2 than that in IDC with histological grade 3 (P = 0.029). The TPL2 overexpression rate in IDC with tumor-node-metastasis (TNM) stage I was significantly higher than that in IDC with TNM stages II-III (P = 0.035). We conclude that TPL2 and Pin1 may synergistically promote the occurrence and development of IDC, but TPL2 overexpression may be an early molecular event in IDC development. TPL2 overexpression is significantly related with IDC with lower malignancy or earlier TNM stage, suggesting that the prognosis of IDC patients with TPL2 overexpression may be better and TPL2 overexpression may be a predictor of good prognosis in IDC.

A genetic mosaic mouse model illuminates the pre-malignant progression of basal-like breast cancer.

Basal-like breast cancer (BLBC) is highly aggressive, and often characterized by BRCA1 and p53 deficiency. Although conventional mouse models enabled the investigation of BLBC at malignant stages, its initiation and pre-malignant progression remain understudied. Here, we leveraged a mouse genetic system known as mosaic analysis with double markers (MADM) to study BLBC initiation by generating rare GFP+Brca1, p53-deficient mammary cells alongside RFP+ wild-type sibling cells. After confirming the close resemblance of mammary tumors arising in this model to human BLBC at both transcriptomic and genomic levels, we focused our studies on the pre-malignant progression of BLBC. Initiated GFP+ mutant cells showed a stepwise pre-malignant progression trajectory from focal expansion to hyper-alveolarization and then to micro-invasion. Furthermore, despite morphological similarities to alveoli, hyper-alveolarized structures actually originate from ductal cells based on twin-spot analysis of GFP-RFP sibling cells. Finally, luminal-to-basal transition occurred exclusively in cells that have progressed to micro-invasive lesions. Our MADM model provides excellent spatiotemporal resolution to illuminate the pre-malignant progression of BLBC, and should enable future studies on early detection and prevention for this cancer.

Circulating neutrophils from patients with early breast cancer have distinct subtype-dependent phenotypes.

PURPOSE: An elevated number of circulating neutrophils is a poor prognostic factor for breast cancer, where evidence of bone marrow cancer-dependent priming is found. However, how early this priming is detectable remains unclear. PATIENTS AND METHODS: Here, we investigate changes in circulating neutrophils from newly diagnosed breast cancer patients before any therapeutic interventions. To do this, we assessed their lifespan and their broader intracellular kinase network activation states by using the Pamgene Kinome assay which measures the activity of neutrophil kinases. RESULTS: We found sub-type specific L-selectin (CD62L) changes in circulating neutrophils as well as perturbations in their overall global kinase activity. Strikingly, breast cancer patients of different subtypes (HR+, HER2+, triple negative) exhibited distinct neutrophil kinase activity patterns indicating that quantifiable perturbations can be detected in circulating neutrophils from early breast cancer patients, that are sensitive to both hormonal and HER-2 status. We also detected an increase in neutrophils lifespan in cancer patients, independently of tumour subtype. CONCLUSIONS: Our results suggest that the tumour-specific kinase activation patterns in circulating neutrophils may be used in conjunction with other markers to identify patients with cancer from those harbouring only benign lesions of the breast. Given the important role neutrophil in breast cancer progression, the significance of this sub-type of specific priming warrants further investigation.

Spectrum of Mucin-containing Lesions of the Breast: Multimodality Imaging Review with Pathologic Correlation.

Mucin-containing lesions of the breast encompass a wide range of benign and malignant processes. The spectrum of histologic findings includes incidental mucus-filled benign cysts or ducts, mucocele-like lesions (MLLs), mucin-producing ductal carcinoma in situ, and invasive mucinous carcinoma. MLL is characterized by the presence of mucin-containing cysts that are typically associated with extravasated stromal mucin. MLL is often benign but can be associated with epithelial atypia or malignancy. Mucinous carcinoma represents the malignant end of the spectrum of mucinous lesions of the breast. Evidence-based literature supports a conservative approach for benign MLLs without associated atypia or malignancy, reserving excision for those lesions exhibiting such pathologic features. The most common imaging finding for MLL is microcalcifications at mammography. No specific imaging feature is predictive of malignant outcome at surgical excision. Invasive mucinous carcinoma is a heterogeneous breast tumor subtype, as defined according to the World Health Organization criteria. Mucinous carcinomas are categorized into pure (>90% mucinous component) or mixed (10%-90% mucinous component) subtypes. Pure mucinous carcinomas are generally associated with excellent prognosis and survival, with a few exceptions. Mixed mucinous carcinomas do not have the same favorable prognosis and instead behave similarly to invasive breast carcinomas of no special type. Characteristic diagnostic imaging features can be identified for mucinous carcinoma based on its mucinous and nonmucinous contents. ©RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.