Ductal carcinoma in situ (DCIS) is a risk factor for subsequent invasive breast cancer (IBC). To identify events in DCIS that lead to invasive cancer, we performed single-cell RNA sequencing on DCIS lesions and matched normal breast tissue. Inferred copy-number variation was used to identify neoplastic epithelial cells from clinical specimens, which contained a mixture of DCIS and normal ducts. Phylogenetic analysis demonstrated intratumoral clonal heterogeneity that was associated with significant gene expression differences. Classification of epithelial cells into mammary cell states revealed that subclones contained a mixture of cell states, suggesting an ongoing pattern of differentiation after neoplastic transformation. Cell state proportions were significantly different based on estrogen receptor expression, with estrogen receptor-negative DCIS more closely resembling the distribution in the normal breast, particularly with respect to cells with basal characteristics. Specific alterations in cell state proportions were associated with progression to invasive cancer in a cohort of DCIS with longitudinal outcome. Ongoing transcription of key basement membrane (BM) genes occurred in specific subsets of epithelial cell states, including basal/myoepithelial, which are diminished in DCIS. In the transition to IBC, the BM protein laminin, but not COL4, was altered in DCIS adjacent to invasion. Loss of COL4, but not laminin, in an in vitro DCIS model led to an invasive phenotype. These findings suggest that the process of invasion is a loss-of-function event due to an imbalance in critical cell populations essential for BM integrity rather than a gain of an invasive phenotype by neoplastic cells.

Single-cell analyses reveal ductal carcinoma in situ comprises multiple genetic clones with significant phenotypic diversity and link alterations in epithelial cell states and basement membrane integrity with invasive breast cancer progression.

Ductal carcinoma in situ (DCIS) is overtreated, in part because of inability to predict which DCIS cases diagnosed at core needle biopsy (CNB) will be upstaged at excision. This study aimed to determine whether quantitative magnetic resonance imaging (MRI) features can identify DCIS at risk of upstaging to invasive cancer.

This prospective observational clinical trial analyzed women with a diagnosis of DCIS on CNB. All the participants underwent preoperative 3T MRI. Quantitative MRI features from routine dynamic contrast-enhanced (DCE) MR images (e.g., peak percent enhancement [PE]) and from advanced high temporal-resolution DCE MR images (e.g., Ktrans) were measured. Clinical, pathologic, and mammographic features were reviewed. Associations with upstaging were summarized using the area under the receiver operating characteristic curve (AUC).

Of 58 DCIS lesions at CNB, 15 (26%) were upstaged to invasive cancer at surgery. Of the 58 lesions, 46 (79%) enhanced on MRI, although enhancement alone was not significantly associated with upstaging (p = 0.71). Among the DCIS lesions that enhanced, higher PE was most strongly associated with upstaging (AUC, 0.81; adjusted p = 0.009) and outperformed MRI features acquired via high temporal resolution DCE-MRI (AUC, 0.50-0.73). Lesion span on MRI was not significantly associated with upstaging risk (AUC, 0.55; adjusted p = 0.61), nor were any clinical, pathologic, or mammographic features (p > 0.24).

Quantitative features acquired from routine clinical breast MRI and advanced DCE-MRI demonstrated good performance in identifying which DCIS lesions were upstaged to invasive cancer at excision. These features may prove valuable for appropriate selection of active surveillance in future DCIS de-escalation trials.

Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer with debated management strategies, particularly in unscreened populations where delayed detection often leads to advanced presentations. Understanding DCIS in this context is crucial for improving risk stratification, treatment, and outcomes.

This study aims to explore the clinicopathologic features, progression, and outcomes of DCIS in an unscreened population, comparing findings with national and international studies.

We conducted a retrospective analysis of 172 patients diagnosed with isolated DCIS at Liaquat National Hospital and Medical College, Karachi, Pakistan, from January 2019 to December 2023. Data collected included demographics, presenting symptoms, imaging findings, biopsy methods, histopathologic features, and treatment details. Statistical analysis was performed using SPSS Statistics for Windows, Version 25 (Released 2017; SPSS Inc., Chicago, United States), with p ≤ 0.05 considered significant.

Of 4690 breast cancer cases, 3.6% were isolated DCIS. The median age was 51 years, with 66% postmenopausal. The most common symptom was a palpable lump (68%), with only 3.5% detected via screening. High-grade DCIS was prevalent (41.7%), with comedo necrosis in 23.7%. Tumor size exceeded 5 cm in 25.8% of cases. Breast-conserving surgery (BCS) was performed in 39.9% of patients, with a 15.4% re-surgery rate. Mastectomy and sentinel lymph node biopsy were required in 56.6% of cases. The upgrade rate to invasive carcinoma was 39.9%, higher than global averages. Estrogen receptor positivity was noted in 70.9% of patients.

DCIS in unscreened populations presents more aggressively, with larger, higher-grade tumors and a significant risk of progression to invasive disease. The findings emphasize the need for targeted screening and tailored management strategies to improve outcomes. Future research should focus on optimizing diagnostic and therapeutic approaches in such high-risk groups.

This systematic review and meta-analysis investigate the added value of structured integration of Breast Imaging Reporting and Data System (BI-RADS) criteria using the Kaiser score (KS) to avoid unnecessary biopsies in BI-RADS 4 lesions.

A systematic review and meta-analysis were conducted using predefined criteria. Eligible articles, published in English until May 2024, dealt with KS in the context of BI-RADS 4 MRI. Two reviewers extracted study characteristics, including true positives (TP), false positives (FP), true negatives (TN), and false negatives (FN). Sensitivity, specificity, negative likelihood ratio, and positive likelihood ratio were calculated using bivariate random effects. Fagan nomograms identified the maximum pre-test probability at which post-test probabilities of a negative MRI aligned with the 2% malignancy rate benchmark for downgrading BI-RADS 4 to BI-RADS 3. I² statistics and meta-regression explored sources of heterogeneity. p-values < 0.05 were considered significant.

Seven studies with 1877 lesions (833 malignant, 1044 benign) were included. The average breast cancer prevalence was 47.3%. Pooled sensitivity was 94.3% (95%-CI 88.9%-97.1%), and pooled specificity was 68.1% (95%-CI 56.6%-77.7%) using a random effects model. Overall, 52/833 cases were FNs (6.2%). Fagan nomograms showed that KS could rule out breast cancer in BI-RADS 4 lesions at a pre-test probability of 20.3% for all lesions, 25.4% for masses, and 15.2% for non-mass lesions.

In MRI-assessed BI-RADS 4 lesions, applying structured BI-RADS criteria with the KS reduces unnecessary biopsies by 70% with a 6.2% FN rate. Breast cancer can be ruled out up to pre-test probabilities of 20.3%.

Question What, if any, value is added by structured integration of BI-RADS criteria using the Kaiser Score (KS) to avoid unnecessary biopsies in BI-RADS 4 lesions? Findings The structured integration of BI-RADS criteria using the Kaiser Score (KS) reduces unnecessary biopsies in BI-RADS 4 lesions by 70%. Clinical relevance The structured approach offered by the Kaiser Score (KS) avoids unnecessary recalls, potentially reducing patient anxiety, lessening the burden on medical personnel, and the need for further imaging and biopsies due to more objective and thus efficient clinical decision-making in evaluating BI-RADS 4 lesions.

Background/Objectives: Ductal carcinoma in situ (DCIS) is the most common non-invasive form of breast cancer. It is not clear to what extent DCIS is a part of the hereditary breast/ovarian cancer syndrome caused by BRCA1/2 mutations. Therefore, we investigated the association of BRCA1/2 mutations in patients with DCIS and assessed their impact on survival. Methods: We studied 564 Polish women with DCIS for six alleles in BRCA1 (c.181T>G, c.5266dupC, c.4035delA, c.3700_3704del5, c.68_69del and c.5251C>T) and four in BRCA2 (c.658_659del, c.3847_3848del, c.5946del and c.7913_7917del). To investigate the association of BRCA1/2 founder mutations with DCIS risk, we tested 4702 controls as a reference. To analyze survival, mutation carriers were followed for an average of 110 months. Results: A BRCA1 mutation was present in seven (1.24%) cases and in twenty-two (0.47%) controls (OR = 3.27, 95%CI 1.36 to 7.87, p = 0.01). A BRCA2 mutation was present in eight (1.42%) cases versus six (0.13%) controls (OR = 11.3, 95%CI 3.9 to 32.6, p < 0.0001). Three of the fifteen cases with BRCA1/2 mutations developed invasive ipsilateral or contralateral breast cancer, on average 6 years from the diagnosis of DCIS. There were no deaths reported among the 15 mutation carriers with DCIS. Conclusions: DCIS is a part of the hereditary breast/ovarian cancer syndrome caused by BRCA1/2 mutations. Women with DCIS should receive genetic counseling and testing for BRCA1/2 mutations. BRCA1/2 mutations may predispose women to a better DCIS prognosis, but further studies are needed.

The standard treatment for ductal carcinoma in situ became well established through the results of several valuable clinical trials, and its therapeutic benefits have now come to be taken for granted. Ductal carcinoma in situ has an extremely good prognosis with the current treatment approach, with a 10-year breast cancer-specific survival rate of 97-98%. According to one retrospective cohort study, the breast cancer-specific survival rate of patients with low-grade ductal carcinoma in situ does not differ significantly between patients undergoing and not undergoing surgery. Some patients with ductal carcinoma in situ are not at a risk of progression to invasive cancer, but the predictors of such progression have not yet been clearly identified. Therefore, the same therapeutic strategies have been used to treat ductal carcinoma in situ and under the assumption that they have risks of invasive breast cancer, and a well-balanced risk/benefit ratio in respect of treatment has not yet been achieved. Based on the results of several recent clinical trials aimed at ensuring provision of a well-balanced treatment for patients with ductal carcinoma in situ which carries a good prognosis, de-escalation of postoperative adjuvant therapy has now begun. Currently, not only is the optimization of postoperative adjuvant therapy accelerating, but also clinical trials to de-escalate basic surgical treatments are under way. There is a possibility of achieving individualized treatment for patients with ductal carcinoma in situ of the breast with reduced treatment intervention. In this review, we present an overview of the current treatment approaches and potential future management strategies for ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) is a noninvasive breast disease that variably progresses to invasive breast cancer (IBC). Given the unpredictability of this progression, most DCIS patients are aggressively managed similar to IBC patients. Undoubtedly, this treatment paradigm places many DCIS patients at risk of overtreatment and its significant consequences. Historically, prognostic modeling has included the assessment of clinicopathological features and genomic markers. Although these provide valuable insights into tumor biology, they remain insufficient to predict which DCIS patients will progress to IBC. Contemporary work has begun to focus on the microenvironment surrounding the ductal cells for molecular patterns that might predict progression. In this review, extracellular microenvironment alterations occurring with the malignant transformation from DCIS to IBC are detailed. Not only do changes in collagen abundance, organization, and localization mediate the transition to IBC, but also the discrete post-translational regulation of collagen fibers is understood to promote invasion. Other extracellular matrix proteins, such as matrix metalloproteases, decorin, and tenascin C, have been characterized for their role in invasive transformation and further demonstrate the prognostic value of the extracellular matrix. Importantly, these extracellular matrix proteins influence immune cells and fibroblasts toward pro-tumorigenic phenotypes. Thus, the progressive changes in the extracellular microenvironment play a key role in invasion and provide promise for prognostic development.

Ductal carcinoma in-situ (DCIS) is a pre-invasive form of invasive breast cancer (IBC). Due to improved breast cancer screening, it now accounts for ~ 25% of all breast cancers. While the treatment success rates are over 90%, this comes at the cost of considerable morbidity, considering that the majority of DCIS never become invasive and our understanding of the molecular changes occurring in DCIS that predispose to invasive disease is limited. The aim of this study is to characterize molecular changes that occur in DCIS, with the goal of improving DCIS risk stratification.

We identified and obtained a total of 197 breast tissue samples from 5 institutions (93 DCIS progressors, 93 DCIS non-progressors, and 11 adjacent normal breast tissues) that had at least 10-year follow-up. We isolated DNA and RNA from archival tissue blocks and characterized genome-wide mRNA expression, DNA methylation, DNA copy number variation, and RNA splicing variation.

We obtained all four genomic data sets in 122 of the 197 samples. Our intrinsic expression subtype-stratified analyses identified multiple molecular differences both between DCIS subtypes and between DCIS and IBC. While there was heterogeneity in molecular signatures and outcomes within intrinsic subtypes, several gene sets that differed significantly between progressing and non-progressing DCIS were identified by Gene Set Enrichment Analysis.

DCIS is a molecularly highly heterogenous disease with variable outcomes, and the molecular events determining DCIS disease progression remain poorly defined. Our genome-wide multi-omic survey documents DCIS-associated alterations and reveals molecular heterogeneity within the intrinsic DCIS subtypes. Further studies investigating intrinsic subtype-stratified characteristics and molecular signatures are needed to determine if these may be exploitable for risk assessment and mitigation of DCIS progression. The highly significant associations of specific gene sets with IBC progression revealed by our Gene Set Enrichment Analysis may lend themselves to the development of a prognostic molecular score, to be validated on independent DCIS cohorts.

This study aimed to develop and validate an ultrasound radiomics model for distinguishing invasive ductal carcinoma (IDC) from ductal carcinoma in situ (DCIS) by combining intratumoral and peritumoral features.

Retrospective analysis was performed on 454 patients from Chengzhong Hospital. The patients were randomly divided in accordance with a ratio of 8:2 into a training group (363 cases) and validation group (91 cases). In addition, 175 patients from Yanghu Hospital were used as the external test group. The peritumoral ranges were set to 2, 4, 6, 8, and 10 mm. Mann-Whitney U-test, recursive feature elimination, and a least absolute shrinkage and selection operator were used to in the dimension reduction of the radiomics features and clinical knowledge, and machine learning logistic regression classifiers were utilized to construct the diagnostic model. The area under the curve (AUC) of the receiver operating characteristics, accuracy, sensitivity, and specificity were used to evaluate the model performance.

By combining peritumoral features of different ranges, the AUC of the radiomics model was improved in the validation and test groups. In the validation group, the maximum increase in AUC was 9.7% (P = 0.031, AUC = 0.803) when the peritumoral range was 8 mm. Similarly, when the peritumoral range was only 8 mm in the test group, the maximum increase in AUC was 4.9% (P = 0.005, AUC = 0.770). In this study, the best prediction performance was achieved when the peritumoral range was only 8 mm.

The ultrasound-based radiomics model that combined intratumoral and peritumoral features exhibits good ability to distinguish between IDC and DCIS. The selection of peritumoral range size exerts an important effect on the prediction performance of the radiomics model.

The current standard of treatment for ductal carcinoma in situ (DCIS) is surgery with or without adjuvant radiotherapy. With a growing debate about overdiagnosis and overtreatment of low-risk DCIS, active surveillance is being explored in several ongoing trials. We conducted a systematic review and meta-analysis to evaluate the recurrence of low-risk DCIS under various treatment approaches.

PubMed, Embase, Web of Science, and Cochrane were searched for studies reporting ipsilateral breast tumour event (IBTE), contralateral breast cancer (CBC), and breast cancer-specific survival (BCSS) rates at 5 and 10 years in low-risk DCIS. The primary outcome was invasive IBTE (iIBTE) defined as invasive progression in the ipsilateral breast.

Thirty three eligible studies were identified, involving 47,696 women with low-risk DCIS. The pooled 5-year and 10-year iIBTE rates were 3.3% (95% confidence interval [CI]: 1.3, 8.1) and 5.9% (95% CI: 3.8, 9.0), respectively. The iIBTE rates were significantly lower in patients who underwent surgery compared to those who did not, at 5 years (3.5% vs. 9.0%, P = 0.003) and 10 years (6.4% vs. 22.7%, P = 0.008). Similarly, the 10-year BCSS rate was higher in the surgery group (96.0% vs. 99.6%, P = 0.010). In patients treated with breast-conserving surgery, additional radiotherapy significantly reduced IBTE risk, but not total-CBC risk.

This review showed a lower risk of progression and better survival in women who received surgery and additional RT for low-risk DCIS. However, our findings were primarily based on observational studies, and should be confirmed with the results from the ongoing trials.

The field cancerization theory suggests that a group of cells containing oncogenic mutations are predisposed to transformation1, 2. We previously identified single cells in BRAF V600E ;p53 -/- zebrafish that reactivate an embryonic neural crest state before initiating melanoma3-5. Here we show that single cells reactivate the neural crest fate from within large fields of adjacent abnormal melanocytes, which we term the "cancer precursor zone." These cancer precursor zone melanocytes have an aberrant morphology, dysplastic nuclei, and altered gene expression. Using single cell RNA-seq and ATAC-seq, we defined a distinct transcriptional cell attractor state for cancer precursor zones and validated the stage-specific gene expression initiation signatures in human melanoma. We identify the cancer precursor zone driver, ID1, which binds to TCF12 and inhibits downstream targets important for the maintenance of melanocyte morphology and cell cycle control. Examination of patient samples revealed precursor melanocytes expressing ID1, often surrounding invasive melanoma, indicating a role for ID1 in early melanomagenesis. This work reveals a surprising field effect of melanoma initiation in vivo in which tumors arise from within a zone of morphologically distinct, but clinically covert, precursors with altered transcriptional fate. Our studies identify novel targets that could improve early diagnosis and prevention of melanoma.

As the benefits of intensive locoregional therapy for ductal carcinoma in situ (DCIS) are realized over time in older adults, life expectancy may help to guide treatment decisions. We examined whether life expectancy was associated with extent of locoregional therapy in this population.

Women ≥ 70 years old with < 5 cm of DCIS diagnosed 2010-2015 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset and categorized by a life expectancy ≤ 5 or > 5 years, defined by a validated claims-based measure. Differences in locoregional therapy (mastectomy + axillary surgery, mastectomy-only, lumpectomy + radiation therapy (RT) + axillary surgery, lumpectomy + RT, lumpectomy-only, and no treatment) by life expectancy were assessed using Pearson chi-squared tests. Generalized linear mixed models were used to identify factors associated with receipt of lumpectomy-only.

Of 5346 women (median age of 75 years, range 70-97 years), 927 (17.3%) had a life expectancy ≤ 5 years. Of the 4041 patients who underwent lumpectomy, 710 (13.3%) underwent axillary surgery. More patients with life expectancy ≤ 5 years underwent lumpectomy-only (39.4% versus 27%), mastectomy-only (8.1% versus 5.3%), or no treatment (5.8% versus 3.2%; p < 0.001). On multivariable analysis, women with life expectancy ≤ 5 years had a significantly greater likelihood of undergoing lumpectomy-only [OR 1.90, 95% CI (1.63-2.22)].

Life expectancy is associated with lower-intensity locoregional therapy for older women with DCIS, yet a large proportion of patients with a life expectancy ≤ 5 years received RT and axillary surgery, highlighting potential overtreatment and opportunities to de-escalate locoregional therapy in older adults.

Ductal carcinoma in situ (DCIS) of the breast is one of the most common pre-invasive cancers diagnosed in women. Quality of life (QoL) is extremely important to assess in studies including these patients due to the favorable prognosis of the disease. The primary objective of this systematic review was to compile a comprehensive list of QoL issues, all existing QoL assessment tools, and patient-reported outcome measures used to assess DCIS.

A search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases from inception to August 2023, using keywords such as "ductal carcinoma in-situ", "quality of life", and "patient-reported outcomes." QoL issues and QoL tools in primary research studies were extracted.

A total of 67 articles identified issues pertaining to patients with DCIS spanning physical, functional, and psychosocial QoL domains. Physical and functional issues observed in patients included pain, fatigue, and impaired sexual functioning. Psychosocial issues such as anxiety, depression, and confusion about one's disease were also common. QoL tools included those that assessed general QoL, breast cancer-specific tools, and issue-specific questionnaires.

The current instruments available to assess QoL in patients with DCIS do not comprehensively capture the issues that are pertinent to patients. Thus, the modification of existing tools or the creation of a DCIS-specific QoL tool is recommended to ensure that future research will be sensitive towards challenges faced by patients with DCIS.

To identify mechanisms underlying the growth of ductal carcinoma in situ (DCIS) and properties that lead to progression to invasive cancer, we performed single-cell RNA-sequencing (scRNA-seq) on DCIS lesions and matched synchronous normal breast tissue. Using inferred copy number variations (CNV), we identified neoplastic epithelial cells from the clinical specimens which contained a mixture of DCIS and normal ducts. Phylogenetic analysis based on the CNVs demonstrated intratumoral clonal heterogeneity was associated with significant gene expression differences. We also classified epithelial cells into mammary cell states and found that individual genetic clones contained a mixture of cell states suggesting an ongoing pattern of differentiation after neoplastic transformation. Cell state proportions were significantly different based on estrogen receptor (ER) expression with ER-DCIS more closely resembling the distribution in the normal breast, particularly with respect to cells with basal characteristics. Using deconvolution from bulk RNA-seq in archival DCIS specimens, we show that specific alterations in cell state proportions are associated with progression to invasive cancer. Loss of an intact basement membrane (BM) is the functional definition of invasive breast cancer (IBC) and scRNA-seq data demonstrated that ongoing transcription of key BM genes occurs in specific subsets of epithelial cell states. Examining BM in archival microinvasive breast cancers and an in vitro model of invasion, we found that passive loss of BM gene expression due to cell state proportion alterations is associated with loss of the structural integrity of the duct leading to an invasive phenotype. Our analyses provide detailed insight into DCIS biology.

Single cell analysis reveals that preinvasive breast cancer is comprised of multiple genetic clones and there is substantial phenotypic diversity both within and between these clones. Ductal carcinoma in situ (DCIS) of the breast is a non-invasive condition commonly identified through mammographic screening. A primary diagnosis of DCIS carries little mortality risk on its own, but its presence is a risk factor for subsequent clonally related invasive breast cancer (IBC) (1-5).

Ductal carcinoma in situ (DCIS) is recognised by the World Health Organisation (WHO) Classification of Tumours (WCT) as a non-invasive neoplastic epithelial proliferation confined to the mammary ducts and lobules. This report categorises the references cited in the DCIS chapter of the 5th edition of the WCT (Breast Tumours) according to prevailing evidence levels for evidence-based medicine and the Hierarchy of Evidence for Tumour Pathology (HETP), identifying potential gaps that can inform subsequent editions of the WCT for this tumour.

We included all citations from the DCIS chapter of the WCT (Breast Tumours, 5th edition). Each citation was appraised according to its study design and evidence level. We developed our map of cited evidence, which is a graphical matrix of tumour type (column) and tumour descriptors (rows). Spheres were used to represent the evidence, with size and colour corresponding to their number and evidence level respectively. Thirty-six publications were retrieved. The cited literature in the DCIS chapter comprised mainly case series and were regarded as low-level. We found an unequal distribution of citations among tumour descriptors. 'Pathogenesis' and 'prognosis and prediction' contained the most references, while 'clinical features', 'aetiology' and 'diagnostic molecular pathology' had only a single citation each. 'Prognosis and prediction' had the greatest proportion of moderate- and high-levels of evidence.

Our findings align with the disposition for observational studies inherent in the field of pathology. Our map is a springboard for future efforts in mapping all available evidence on DCIS, potentially augmenting the editorial process and future editions of WCTs.

New approaches are needed to determine which ductal carcinoma in situ (DCIS) is at high risk for progression to invasive ductal carcinoma (IDC). We retrospectively studied DCIS patients who declined surgery (2002-2019), and received endocrine therapy (ET) and breast MRI. Baseline MRI and changes at 3 months and 6 months were analyzed by recursive partitioning to stratify IDC risk. Sixty-two patients (63 DCIS; 1 bilateral) with a mean follow-up of 8.5 years were included. Fifty-one percent remained on active surveillance (AS) without evidence of IDC, with a mean duration of 7.6 years. A decision tree based on MRI features of lesion distinctness and background parenchymal enhancement (BPE) at baseline and change after 3 months of ET stratified patients into low, intermediate, and high risk for progression to IDC. MRI imaging features in patients treated with ET and undergoing AS, may help determine which DCIS lesions are at low versus high risk for IDC.

Ductal carcinoma in situ (DCIS) accounts for approximately 30% of new breast cancer diagnoses. However, our understanding of how normal breast tissue evolves into DCIS and invasive cancers remains insufficient. Further, conclusions regarding the mechanisms of disease progression in terms of histopathology, genetics, and radiology are often conflicting and have implications for treatment planning. Moreover, the increase in DCIS diagnoses since the adoption of organized breast cancer screening programs has raised concerns about overdiagnosis and subsequent overtreatment. Active monitoring, a nonsurgical management strategy for DCIS, avoids surgery in favor of close imaging follow-up to de-escalate therapy and provides more treatment options. However, the two major challenges in active monitoring are identifying occult invasive cancer and patients at risk of invasive cancer progression. Subsequently, four prospective active monitoring trials are ongoing to determine the feasibility of active monitoring and refine the patient eligibility criteria and follow-up intervals. Radiologists play a major role in determining eligibility for active monitoring and reviewing surveillance images for disease progression. Trial results published over the next few years would support a new era of multidisciplinary DCIS care.

Risk of recurrence and progression of ductal carcinoma in situ (DCIS) to invasive cancer remains uncertain, emphasizing the need for developing predictive biomarkers of aggressive DCIS.

Human cell lines and mouse models of disease progression were analyzed for candidate risk predictive biomarkers identified and validated in two independent DCIS cohorts.

RNA profiling of normal mammary and DCIS tissues (n = 48) revealed that elevated SOX11 expression correlates with MKI67, EZH2, and DCIS recurrence score. The 21T human cell line model of DCIS progression to invasive cancer and two mouse models developing mammary intraepithelial neoplasia confirmed the findings. AKT activation correlated with chromatin accessibility and EZH2 enrichment upregulating SOX11 expression. AKT and HER2 inhibitors decreased SOX11 expression along with diminished mammosphere formation. SOX11 was upregulated in HER2+ and basal-like subtypes (P < 0.001). Longitudinal DCIS cohort (n = 194) revealed shorter recurrence-free survival in SOX11+ than SOX11- patients (P = 0.0056 in all DCIS; P < 0.0001 in HER2+ subtype) associated with increased risk of ipsilateral breast event/IBE (HR = 1.9, 95%CI = 1.2-2.9; P = 0.003).

Epigenetic activation of SOX11 drives recurrence of DCIS and progression to invasive cancer, suggesting SOX11 as a predictive biomarker of IBE.

Ductal-carcinoma in situ (DCIS) is a pre-invasive form of breast cancer with good prognosis. Follow-up guidelines in the Netherlands are currently the same as for invasive breast cancer. Due to fear of invasive breast cancer or recurrence, it is hypothesized that follow-up for DCIS after treatment is more intense in practice resulting in potentially unnecessary high costs. This study investigates the follow-up in practice for patients with DCIS compared to the recommendations in order to inform clinicians and policy makers how to utilize these guidelines.

Patients diagnosed with pure DCIS between 2004 and 2014 were followed up until 2018. Information on duration and frequency of follow-up visits, reasons and decision makers for shortening, and prolonging follow-up was collected. Prolonged follow-up was defined as deviation from the Dutch guideline: more than 5 years of follow-up and older than 60 years.

Of the 227 patients the mean number of visits per year was 1.4 and mean years of follow-up was 6.0. Thirty-three percent had prolonged follow-up and 26% shorter follow-up than recommended. A majority (78%) of decision for prolonged follow-up was being made by clinicians.

Follow-up duration is in almost half of patients with DCIS according to guidelines and with most prolonged follow-up only up to a year longer than recommended. In most cases suspicious findings and the timing of the population screening program appeared to cause prolonged follow-up. If accepted by patients and clinicians, future DCIS specific guidelines should address these reasons and tailor to the individual risks.

Ductal carcinoma in situ with microinvasion (DCISM) is a challenging subtype of breast cancer with controversial invasiveness and prognosis. Accurate diagnosis of DCISM from ductal carcinoma in situ (DCIS) is crucial for optimal treatment and improved clinical outcomes. However, there are often some suspicious small cancer nests in DCIS, and it is difficult to diagnose the presence of intact myoepithelium by conventional hematoxylin and eosin (H&E) stained images. Although a variety of biomarkers are available for immunohistochemical (IHC) staining of myoepithelial cells, no single biomarker is consistently sensitive to all tumor lesions. Here, we introduced a new diagnostic method that provides rapid and accurate diagnosis of DCISM using multiphoton microscopy (MPM). Suspicious foci in H&E-stained images were labeled as regions of interest (ROIs), and the nuclei within these ROIs were segmented using a deep learning model. MPM was used to capture images of the ROIs in H&E-stained sections. The intensity of two-photon excitation fluorescence (TPEF) in the myoepithelium was significantly different from that in tumor parenchyma and tumor stroma. Through the use of MPM, the myoepithelium and basement membrane can be easily observed via TPEF and second-harmonic generation (SHG), respectively. By fusing the nuclei in H&E-stained images with MPM images, DCISM can be differentiated from suspicious small cancer clusters in DCIS. The proposed method demonstrated good consistency with the cytokeratin 5/6 (CK5/6) myoepithelial staining method (kappa coefficient = 0.818).

Artificial intelligence (AI) has been implemented in multiple fields of medicine to assist in the diagnosis and treatment of patients. AI implementation in radiology, more specifically for breast imaging, has advanced considerably. Breast cancer is one of the most important causes of cancer mortality among women, and there has been increased attention towards creating more efficacious methods for breast cancer detection utilizing AI to improve radiologist accuracy and efficiency to meet the increasing demand of our patients. AI can be applied to imaging studies to improve image quality, increase interpretation accuracy, and improve time efficiency and cost efficiency. AI applied to mammography, ultrasound, and MRI allows for improved cancer detection and diagnosis while decreasing intra- and interobserver variability. The synergistic effect between a radiologist and AI has the potential to improve patient care in underserved populations with the intention of providing quality and equitable care for all. Additionally, AI has allowed for improved risk stratification. Further, AI application can have treatment implications as well by identifying upstage risk of ductal carcinoma in situ (DCIS) to invasive carcinoma and by better predicting individualized patient response to neoadjuvant chemotherapy. AI has potential for advancement in pre-operative 3-dimensional models of the breast as well as improved viability of reconstructive grafts.

Breast cancer becomes invasive when carcinoma cells invade through the basement membrane (BM)-a nanoporous layer of matrix that physically separates the primary tumour from the stroma. Single cells can invade through nanoporous three-dimensional matrices due to protease-mediated degradation or force-mediated widening of pores via invadopodial protrusions. However, how multiple cells collectively invade through the physiological BM, as they do during breast cancer progression, remains unclear. Here we developed a three-dimensional in vitro model of collective invasion of the BM during breast cancer. We show that cells utilize both proteases and forces-but not invadopodia-to breach the BM. Forces are generated from a combination of global cell volume expansion, which stretches the BM, and local contractile forces that act in the plane of the BM to breach it, allowing invasion. These results uncover a mechanism by which cells collectively interact to overcome a critical barrier to metastasis.

Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited.

We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis.

Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18-137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06-41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7-2.3%) experienced axillary lymph node metastasis.

Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.

Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25-60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.

Fibroids and endometriosis are sex hormone-mediated and exhibit cancer-like behavior. Breast cancer may be more common in women who have had these conditions, but the literature is conflicting and does not always address factors like hysterectomy/oophorectomy status, race/ethnicity, menopause, and hormone receptor subtypes.

Data are from the Sister Study, a cohort of 50,884 U.S. women enrolled in 2003 to 2009 and followed through 2020. Cox proportional hazards models with time-varying exposures and covariates assessed the relationship of fibroids or endometriosis with breast cancer. Logistic regression examined the association with estrogen receptor (ER) status among cases.

Fibroids (19,932 cases) were positively associated with breast cancer [fully adjusted HR: 1.07; 95% confidence interval (CI): 1.01-1.14], notably among Black participants (HR: 1.34; 95% CI: 1.07-1.69) and women who had a hysterectomy (HR: 1.18; 95% CI: 1.05-1.31). Endometriosis (3,970 cases) was not associated with breast cancer (HR: 0.99; 95% CI: 0.91-1.08). Among 4,419 breast cancer cases, fibroids were positively associated with ER+ subtypes (OR: 1.34; 95% CI: 1.10-1.65), while endometriosis was negatively associated with ER+ subtypes (OR: 0.78; 95% CI: 0.61-1.01).

We observed a modest positive association between fibroids and breast cancer, particularly ER+ breast cancer. No relationship with endometriosis and breast cancer incidence was found.

Fibroids, even in those with a family history of breast cancer, might modify breast cancer risk stratification tools. Future studies should further assess this link and interrogate shared risk factors.

Ductal carcinoma in situ (DCIS) is the most common form of noninvasive breast cancer and is associated with an excellent prognosis. As a result, there is concern about overdiagnosis and overtreatment of DCIS because most patients with DCIS are treated as though they have invasive breast cancer and undergo either breast-conserving surgery (BCS)-most commonly followed by radiation therapy (RT)-or mastectomy. Little research to date has focused on nonclinical factors influencing treatments for DCIS.

Population-based data were analyzed from five state cancer registries (California, Florida, New Jersey, New York, and Texas) on women aged 65 years and older newly diagnosed with DCIS during the years 2003 to 2014 using a retrospective cohort design and multinominal logistic modeling. The registry records with Medicare enrollment data and fee-for-service claims to obtain treatments (BCS alone, BCS with RT, or mastectomy) were merged. Surgeon practice structure was identified through physician surveys and internet searches.

Patients of surgeons employed by cancer centers or health systems were less likely to receive BCS with RT or mastectomy than patients of surgeons in single specialty or multispecialty practices. There also was substantial geographic variation in treatments, with patients in New York, New Jersey, and California being less likely to receive BCS with RT or mastectomy than patients in Texas or Florida.

These findings suggest nonclinical factors including the culture of the practice and/or financial incentives are significantly associated with the types of treatment received for DCIS. Increasing awareness and targeted efforts to educate physicians about DCIS management among older women with low-grade DCIS could reduce patient harm and yield substantial cost savings.

Ductal carcinoma in situ is very rare in male patients, accounting for approximately 5%-7% of all male breast cancers. We present a case of a man in his early 70s who presented with bloody nipple discharge and gynaecomastia and was subsequently diagnosed with ductal carcinoma in situ (DCIS). We discuss his management with surgical resection and the consideration of adjuvant treatment. We also review the existing literature on the presentation, diagnosis and management of DCIS in men.

Ductal carcinoma in situ (DCIS) is a nonobligate precursor to invasive cancer that classically presents as asymptomatic calcifications on screening mammography. The increase in DCIS diagnoses with organized screening programs has raised concerns about overdiagnosis, while a patientcentric push for more personalized care has increased awareness about DCIS overtreatment. The standard of care for most new DCIS diagnoses is surgical excision, but nonsurgical management via active monitoring is gaining attention, and multiple clinical trials are ongoing. Imaging, along with demographic and pathologic information, is a critical component of active monitoring efforts. Commonly used imaging modalities including mammography, ultrasound, and MRI, as well as newer modalities such as contrast-enhanced mammography and dedicated breast PET, can provide prognostic information to risk stratify patients for DCIS active monitoring eligibility. Furthermore, radiologists will be responsible for closely surveilling patients on active monitoring and identifying if invasive progression occurs. Active monitoring is a paradigm shift for DCIS care, but the success or failure will rely heavily on the interpretations and guidance of radiologists.

Unnecessary axillary surgery can potentially be avoided in patients with DCIS undergoing mastectomy. Current guidelines recommend upfront sentinel lymph node biopsy during the index operation due to the potential of upstaging to invasive cancer. This study reviews a single institution's experience with de-escalating axillary surgery using superparamagnetic iron oxide dye for axillary mapping in patients undergoing mastectomy for DCIS.

This is a retrospective single-institution cross-sectional study. All medical records of patients who underwent mastectomy for a diagnosis of DCIS from August 2021 to January 2023 were reviewed and patients who had SPIO injected at the time of the index mastectomy were included in the study. Descriptive statistics of demographics, clinical information, pathology results, and interval sentinel lymph node biopsy were performed.

A total of 41 participants underwent 45 mastectomies for DCIS. The median age of the participants was 58 years (IQR = 17; range 25 to 76 years), and the majority of participants were female (97.8%). The most common indication for mastectomy was diffuse extent of disease (31.7%). On final pathology, 75.6% (34/45) of mastectomy specimens had DCIS without any type of invasion and 15.6% (7/45) had invasive cancer. Of the 7 cases with upgrade to invasive disease, 2 (28.6%) of them underwent interval sentinel lymph node biopsy. All sentinel lymph nodes biopsied were negative for cancer.

The use of superparamagnetic iron oxide dye can prevent unnecessary axillary surgery in patients with DCIS undergoing mastectomy.

In total mastectomy (TM), sentinel lymph node biopsy (SLNB) is recommended but can be omitted for breast-conserving surgery (BCS) in patients with ductal carcinoma in situ (DCIS). However, concerns regarding SLNB-related complications and their impact on quality of life exist. Consequently, further research is required to evaluate the role of axillary surgeries, including SLNB, in the treatment of TM. We aimed to explore the clinicopathological factors and outcomes associated with axillary surgery in patients with a final diagnosis of pure DCIS who underwent BCS or TM.

We retrospectively analyzed large-scale data from the Korean Breast Cancer Society registration database, highlighting on patients diagnosed with pure DCIS who underwent surgery and were categorized into two groups: BCS and TM. Patients were further categorized into surgery and non-surgery groups according to their axillary surgery status. The analysis compared clinicopathological factors and outcomes according to axillary surgery status between the BCS and TM groups.

Among 18,196 patients who underwent surgery for DCIS between 1981 and 2022, 11,872 underwent BCS and 6,324 underwent TM. Both groups leaned towards axillary surgery more frequently for large tumors. In the BCS group, clinical lymph node status was associated with axillary surgery (odds ratio, 11.101; p = 0.003). However, in the TM group, no significant differences in these factors were observed. Survival rates did not vary between groups according to axillary surgery performance.

The decision to perform axillary surgery in patients with a final diagnosis of pure DCIS does not affect the prognosis, regardless of the breast surgical method. Furthermore, regardless of the breast surgical method, axillary surgery, including SLNB, should be considered for high-risk patients, such as those with large tumors. This may reduce unnecessary axillary surgery and enhance the patients' quality of life.

With progress in treatments, breast ductal carcinoma in situ (DCIS) outcomes have substantially improved. However, as various treatment methods are used in different countries and institutions, consensus on the optimal treatment method is lacking. This study aimed to analyze the prognostic factors and provide a reference for optimizing the clinical treatment of DCIS.

This retrospective clinical study collected data from DCIS patients at the Sun Yat-sen University Cancer Center from 2010 to 2017. The Kaplan-Meier method and Cox regression model were used to assess disease-free survival (DFS), overall survival (OS), and local control (LC) rates.

Among the 483 included patients, 83.6% (404) underwent mastectomies. The median follow-up time was 101 months. The number of patients undergoing breast-conserving surgery (BCS) with radiotherapy has gradually increased. Axillary lymph node dissection was the main surgery performed from 2010 to 2015, and the proportion of sentinel lymph node biopsies (SLNBs) has increased. LC and DFS rates with BCS without radiotherapy were significantly lower than those with mastectomy (P = .002; P < .001). Additionally, the patients who did not undergo axillary surgery had worse LC and OS rates than those who underwent SLNB (P = .028 and P = .038). Endocrine therapy (ET) or its duration had no significant effect on prognosis.

In conclusion, BCS without radiotherapy and lack of axillary surgery were independent prognostic factors. We recommend performing BCS with radiotherapy and SLNB more in clinical practice, as well as shortening the ET duration.

A 2 mm resection margin is considered adequate for ductal carcinoma in situ (DCIS). We assessed the effectiveness of a tailored radiation dose for margins < 2 mm and the appropriate margin width for high-risk DCIS. We retrospectively evaluated 137 patients who received adjuvant radiotherapy after breast-conserving surgery for DCIS between 2013 and 2019. The patients were divided into three- positive, close (< 2 mm), and negative (≥ 2 mm) margin groups. Radiation dose to the tumor bed in equivalent dose in 2 Gy fractions were a median of 66.25 Gy, 61.81 Gy, and 59.75 Gy for positive, close, and negative margin groups, respectively. During a median follow-up of 58 months, the crude rates of local recurrence were 15.0%, 6.7%, and 4.6% in the positive, close, and negative margin groups, respectively. The positive margin group had a significantly lower 5-year local recurrence-free survival (LRFS) rate compared to the close and negative margin groups in propensity-weighted log-rank analysis (84.82%, 93.27%, and 93.20%, respectively; p = 0.008). The difference in 5-year LRFS between patients with the high- and non-high-grade tumors decreased as the margin width increased (80.4% vs. 100.0% for margin ≥ 2 mm, p < 0.001; 92.3% vs. 100.0% for margin ≥ 6 mm, p = 0.123). With the radiation dose tailored for margin widths, positive margins were associated with poorer local control than negative margins, whereas close margins were not. Widely clear margins (≥ 2 mm) were related to favorable local control for high-grade DCIS.

The LOw RISk DCIS (LORIS) study was set up to compare conventional surgical treatment with active monitoring in women with ductal carcinoma in situ (DCIS). Recruitment to trials with a surveillance arm is known to be challenging, so strategies to maximise patient recruitment, aimed at both patients and recruiting centres, were implemented.

Women aged ≥ 46 years with a histologically confirmed diagnosis of non-high-grade DCIS were eligible for 1:1 randomisation to either surgery or active monitoring. Prior to randomisation, all eligible women were invited to complete: (1) the Clinical Trials Questionnaire (CTQ) examining reasons for or against participation, and (2) interviews exploring in depth opinions about the study information sheets and film. Women agreeing to randomisation completed validated questionnaires assessing health status, physical and mental health, and anxiety levels. Hospital site staff were invited to communication workshops and refresher site initiation visits to support recruitment. Their perspectives on LORIS recruitment were collected via surveys and interviews.

Eighty percent (181/227) of eligible women agreed to be randomised. Over 40% of participants had high anxiety levels at baseline. On the CTQ, the most frequent most important reasons for accepting randomisation were altruism and belief that the trial offered the best treatment, whilst worries about randomisation and the influences of others were the most frequent most important reasons for declining. Most women found the study information provided clear and useful. Communication workshops for site staff improved knowledge and confidence but only about half said they themselves would join LORIS if eligible. The most common recruitment barriers identified by staff were low numbers of eligible patients and patient preference.

Recruitment to LORIS was challenging despite strategies aimed at both patients and site staff. Ensuring that recruiting staff support the study could improve recruitment in similar future trials.

ISRCTN27544579, prospectively registered on 22 May 2014.

The chemokine stromal cell-derived-factor 1 (SDF)-1/CXCL12 acts by binding to its receptors, the CXC-4 chemokine receptor (CXCR4) and the CXC-7 chemokine receptor (CXCR7). The binding of CXCL12 to its receptors results in downstream signaling that leads to cell survival, proliferation and migration of tumor cells. CXCL12 and CXCR4 are highly expressed in breast cancer (BC) and glioblastoma (GBM) compared to normal cells. High expression of this chemokine axis correlates with increased therapy resistance and grade, tumor spread and poorer prognosis in these tumors. Tamoxifen (TMX) is a selective estrogen receptor modulator (SERM) that inhibits the expression of estrogen-regulated genes, including growth and angiogenic factors secreted by tumor cells. Additionally, TMX targets several proteins, such as protein kinase C (PKC), phospholipase C (PLC), P-glycoprotein (PgP), phosphatidylinositol-3-kinase (PI3K) and ion channels. This drug showed promising antitumor activity against both BC and GBM cells. In this review, we discuss the role of the CXCL12-CXCR4-CXCR7 chemokine axis in BC and GBM tumor biology and propose TMX as a potential modulator of this axis in these tumors. TMX modulates the CXCL12-CXCR4-CXCR7 axis in BC, however, there are no studies on this in GBM. We propose that studying this axis in GBM cells/patients treated with TMX might be beneficial for these patients. TMX inhibits important signaling pathways in these tumors and the activation of this chemokine axis is associated with increased therapy resistance.

DCIS detection has increased dramatically since the introduction of screening mammography. Current guidance concordant care recommends surgical intervention for all patients with DCIS, followed by radiation and/or endocrine therapy for some. Adjuvant therapies after surgical excision have reduced recurrence rates but not breast cancer mortality. Given the lack of evidence of current treatment regimens and the morbidity associated with these treatments, there is concern that DCIS is over-treated. Active surveillance may be a favorable alternative for selected patients and is currently being investigated through four international clinical trials.

Breast MRI has high sensitivity and negative predictive value, making it well suited to problem solving when other imaging modalities or physical examinations yield results that are inconclusive for the presence of breast cancer. Indications for problem-solving MRI include equivocal or uncertain imaging findings at mammography and/or US; suspicious nipple discharge or skin changes suspected to represent an abnormality when conventional imaging results are negative for cancer; lesions categorized as Breast Imaging Reporting and Data System 4, which are not amenable to biopsy; and discordant radiologic-pathologic findings after biopsy. MRI should not precede or replace careful diagnostic workup with mammography and US and should not be used when a biopsy can be safely performed. The role of MRI in characterizing calcifications is controversial, and management of calcifications should depend on their mammographic appearance because ductal carcinoma in situ may not appear enhancing on MR images. In addition, ductal carcinoma in situ detected solely with MRI is not associated with a higher likelihood of an upgrade to invasive cancer compared with ductal carcinoma in situ detected with other modalities. MRI for triage of high-risk lesions is a subject of ongoing investigation, with a possible future role for MRI in decreasing excisional biopsies. The accuracy of MRI is likely to increase with the use of advanced techniques such as deep learning, which will likely expand the indications for problem-solving MRI. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.