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Background: Consensus guidelines recommend ≥ 2 mm margins in patients undergoing partial mastectomy (PM) for ductal carcinoma in situ (DCIS). It is unknown whether the number or proximity of margins less than 2 mm is associated with an increased mastectomy rate in patients attempting breast conservation therapy (BCT) for DCIS. The aim of this study is to examine this relationship. Patients and Methods: An institutional database review identified 208 patients with DCIS who underwent PM at a tertiary referral center and community hospitals from July 2020 to June 2023. Patients with a history of breast cancer, previous surgery for breast cancer, ipsilateral invasive carcinoma, papillary carcinoma, Paget's disease, more lobular carcinoma in situ (LCIS) than DCIS present, initial mastectomy, no DCIS present, routine shave margins (of all vectors), and ≥ 2 mm margins of all six vectors were excluded. Selective intraoperative margin re-excisions were included. Results: A total of 208 patients who met inclusion criteria were retrospectively reviewed. 122 (25%) had one close/positive (< 2 mm) margin and 86 (18%) had two or more close/positive margins. Of the patients with one close/positive margin, 7% (9/122) eventually underwent mastectomy. Of the patients with two or more close/positive margins, 20% (17/86) eventually underwent mastectomy. Overall, no patients with opposing margins underwent mastectomy. Conclusions: Patients undergoing PM for DCIS have a mastectomy rate that is increased threefold, with two or more close/positive margins at initial PM, when compared with those with only one close/positive margin. The presence of opposing close/positive margins at initial PM did not increase the mastectomy rate and most were cleared with re-excision. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is characterised by a high level of heterogeneity, which is influenced by the interaction of neoplastic cells with the tumour microenvironment. The diagnostic and prognostic role of the tumour stroma in BC remains to be defined. Differential interference contrast (DIC) microscopy is a label‐free imaging technique well suited to visualise weak optical phase objects such as cells and tissue. This study aims to compare stromal collagen fibre characteristics between in situ and invasive breast tumours using DIC microscopy and investigate the prognostic value of collagen parameters in BC. A tissue microarray was generated from 200 cases, comprising ductal carcinoma in situ (DCIS; n = 100) and invasive tumours (n = 100) with an extra 50 (25 invasive BC and 25 DCIS) cases for validation was utilised. Two sections per case were used: one stained with haematoxylin and eosin (H&E) stain for histological review and one unstained for examination using DIC microscopy. Collagen fibre parameters including orientation angle, fibre alignment, fibre density, fibre width, fibre length and fibre straightness were measured. Collagen fibre density was higher in the stroma of invasive BC (161.68 ± 11.2 fibre/µm2) compared to DCIS (p < 0.0001). The collagen fibres were thinner (13.78 ± 1.08 µm), straighter (0.96 ± 0.006, on a scale of 0–1), more disorganised (95.07° ± 11.39°) and less aligned (0.20 ± 0.09, on a 0–1 scale) in the invasive BC compared to DCIS (all p < 0.0001). A model considering these features was developed that could distinguish between DCIS and invasive tumours with 94% accuracy. There were strong correlations between fibre characteristics and clinicopathological parameters in both groups. A statistically significant association between fibre characteristics and patients’ outcomes (breast cancer specific survival, and recurrence free survival) was observed in the invasive group but not in DCIS. Although invasive BC and DCIS were both associated with stromal reaction, the structural features of collagen fibres were significantly different in the two disease stages. Analysis of the stroma fibre characteristics in the preoperative core biopsy specimen may help to differentiate pure DCIS from those associated with invasion. [ABSTRACT FROM AUTHOR]

Background: Ductal carcinoma in situ (DCIS) of the breast is an early stage of breast cancer, and preventing its progression to invasive ductal carcinoma (IDC) is crucial for the early detection and treatment of breast cancer. Although single-cell transcriptome analysis technology has been widely used in breast cancer research, the biological mechanisms underlying the transition from DCIS to IDC remain poorly understood. Results: We identified eight cell types through cell annotation, finding significant differences in T cell proportions between DCIS and IDC. Using this as a basis, we performed pseudotime analysis on T cell subpopulations, revealing that differentially expressed genes primarily regulate immune cell migration and modulation. By intersecting WGCNA results of T cells highly correlated with the subtypes and the differentially expressed genes, we identified six key genes: FGFBP2, GNLY, KLRD1, TYROBP, PRF1, and NKG7. Excluding PRF1, the other five genes were significantly associated with overall survival in breast cancer, highlighting their potential as prognostic biomarkers. Conclusions: We identified immune cells that may play a role in the progression from DCIS to IDC and uncovered five key genes that can serve as prognostic markers for breast cancer. These findings provide insights into the mechanisms underlying the transition from DCIS to IDC, offering valuable perspectives for future research. Additionally, our results contribute to a better understanding of the biological processes involved in breast cancer progression. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Retrospective observational studies suggest a potential role of beta-blockers as a protective strategy against progression and metastasis in invasive breast cancer. In this context, we investigated the impact of beta-blocker exposure on risk for progression to invasive breast cancer after diagnosis of ductal cancer in situ (DCIS). Methods: The retrospective study population included 2535 women diagnosed with pure DCIS between 2006 and2012 in three healthcare regions in SwedenExposure to beta-blocker was quantified using a time-varying percentage of days with medication available. The absolute risk was quantified using cumulative incidence functions and cox models were applied to quantify the association between beta-blocker exposure and time from DCIS diagnosis to invasive breast cancer, accounting for delayed effects, competing risks and pre-specified confounders. Results: The median follow-up was 8.7 years. One third of the patients in our cohort were exposed to beta-blockers post DCIS diagnosis. During the study period, 48 patients experienced an invasive recurrence, giving a cumulative incidence of invasive breast cancer progression of 1.8% at five years. The cumulative exposure to beta-blocker was associated with a reduced risk in a dose-dependent manner, though the effect was not statistically significant. Conclusion: Our observational study is suggestive of a protective effect of beta-blockers against invasive breast cancer after primary DCIS diagnosis. These results provide rationales for experimental and clinical follow-up studies in carefully selected DCIS groups. [ABSTRACT FROM AUTHOR]

Abstract Background Ductal carcinoma in situ (DCIS) of the breast is an early stage of breast cancer, and preventing its progression to invasive ductal carcinoma (IDC) is crucial for the early detection and treatment of breast cancer. Although single-cell transcriptome analysis technology has been widely used in breast cancer research, the biological mechanisms underlying the transition from DCIS to IDC remain poorly understood. Results We identified eight cell types through cell annotation, finding significant differences in T cell proportions between DCIS and IDC. Using this as a basis, we performed pseudotime analysis on T cell subpopulations, revealing that differentially expressed genes primarily regulate immune cell migration and modulation. By intersecting WGCNA results of T cells highly correlated with the subtypes and the differentially expressed genes, we identified six key genes: FGFBP2, GNLY, KLRD1, TYROBP, PRF1, and NKG7. Excluding PRF1, the other five genes were significantly associated with overall survival in breast cancer, highlighting their potential as prognostic biomarkers. Conclusions We identified immune cells that may play a role in the progression from DCIS to IDC and uncovered five key genes that can serve as prognostic markers for breast cancer. These findings provide insights into the mechanisms underlying the transition from DCIS to IDC, offering valuable perspectives for future research. Additionally, our results contribute to a better understanding of the biological processes involved in breast cancer progression.

Abstract Background With the development of novel anti-HER2 targeted drugs, such as ADCs, it has become increasingly important to accurately interpret HER2 expression in breast cancer. Previous studies have demonstrated high intra-observer and inter-observer variabilities in evaluating HER2 staining by human eyes. There exists a strong requirement to develop artificial intelligence (AI) systems to achieve high-precision HER2 expression scoring for better clinical therapy. Methods In the present study, we collected breast cancer tissue samples and stained consecutive sections with anti-Calponin and anti-HER2 antibodies. High-quality digital images were selected from immunohistochemical slides and interpreted as HER2 3+, 2+, 1+, and 0. AI models were trained and assessed using annotated training and testing sets. The AI model was trained to automatically identify ductal carcinoma in situ (DCIS) by Calponin staining and myoepithelial annotation and filter out DCIS components in HER2-stained slides using image-overlapping techniques. Furthermore, we organized two-phase validation studies. In phase one, pathologists interpreted 112 HER2 whole-slide images (WSIs) without AI assistance, whereas in phase two, pathologists read the same slides using the AI system after a washing period of 2 weeks. Results Our AI model greatly improved the accuracy of reading (0.902 vs. 0.710). The number of HER2 1 + patients misdiagnosed as HER2 0 was significantly reduced (32/279 vs. 65/279), and they benefitted from ADC drugs. In addition, the AI algorithm improved the intra-group consistency of HER2 readings by pathologists with different years of experience (intra-class correlation coefficient [ICC]: 0.872–0.926 vs. 0.818–0.908), with the improvement most pronounced among junior pathologists (0.885 vs. 0.818). Conclusions We proposed a high-precision AI system to identify and filter out DCIS components and automatically evaluate HER2 expression in invasive breast cancer.

Purpose: Trials demonstrating benefits of tamoxifen for women with ductal carcinoma in situ (DCIS) were published > 20 years ago; yet subsequent uptake of endocrine therapy was low. We estimated endocrine therapy initiation in women with DCIS between 2001 and 2018 in a community setting, reflecting more recent years of diagnosis than previous studies. Methods: This retrospective cohort included adult females ≥ 20 years diagnosed with first primary DCIS between 2001 and 2018, followed through 2019, and enrolled in one of three U.S. integrated healthcare systems. We collected data on endocrine therapy dispensings (tamoxifen, aromatase inhibitors [AIs]) from electronic pharmacy records within 12 months after DCIS diagnosis. Using generalized linear models with a log link and Poisson distribution, we estimated endocrine therapy initiation rates over time and by patient, tumor (including estrogen receptor [ER] status), and treatment characteristics. Results: Among 2020 women with DCIS, 587 (29%) initiated endocrine therapy within 12 months after diagnosis (36% among 1208 women with ER-positive DCIS). Among women who used endocrine therapy, 506 (86%) initiated tamoxifen and 81 (14%) initiated AIs. Age-adjusted endocrine therapy initiation declined from 34 to 21% between 2001 and 2017; between 2015 and 2018, AI use increased from 8 to 35%. Women less likely to initiate endocrine therapy were ER-negative or had borderline/unknown or no ER test results, ≥ 65 years at diagnosis, Black, and received no radiotherapy. Conclusion: One-third of women diagnosed with DCIS initiated endocrine therapy, and use decreased over time. Understanding why women eligible for endocrine therapy do not initiate is important to maximizing disease-free survival following DCIS diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background A better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells. Methods We utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results. Results We revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown. Conclusions Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.

Male breast cancer is a rare entity consisting of less than 1% of all breast cancer diagnoses, in which pure ductal carcinoma in situ (DCIS) without an invasive component accounts for approximately 10% of these diagnoses. Early diagnosis and appropriate management are essential to ensure favorable outcomes. We present a rare case of mammographically and sonographically occult pure DCIS in a male patient presenting with unilateral bloody nipple discharge, highlighting imaging features and the potential utility of breast MRI that aided diagnosis and management.

Background: A better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells. Methods: We utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results. Results: We revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown. Conclusions: Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state. [ABSTRACT FROM AUTHOR]

Now, targeted therapy and immunotherapy are promoted. tumour -Associated Macrophages (TAMs) are an essential component of immune-response in breast cancer(BC) with prognostic controversy. Additionally, their recruiting factors are still obscure. Purpose:This study aimed to evaluate the prognostic significance of CD163 and CD47 in BC of No Special Type (BC-NST) and to explore their suggested role in recruiting TAMs. This immunohistochemical study was conducted on 91 archival specimens of breast cases. Immunoreactivity scores were correlated with TAMs density, clinicopathological data, and survival. Revealed the highest CD163 expression was detected in the pure DCIS group (p = 0.016), while the highest CD47 expression and high TAMs density were reported in the invasive group (p = 0.008, and p = 0.002 respectively) followed by the DCIS group. In IC-NSTs the CD163 and CD47 scores were associated with poor prognostic parameters like(high grade, advanced stage, distant metastasis, ER negativity,Ki67 index, post-surgical chemotherapy, poor NPI group, high mitotic count, dense infiltration of TAMs, shorter OS). Also, CD47 was associated with the dens infiltration of TAMs in DCIS (p = 0.001). There was a significant correlation between tumour cell expression of CD163 and CD47 in IC-NSTs and DCIS (p = 0.002 and p = 0.009 respectively). High CD163 and CD47 expressions in both DCIS andIBC are intimately associated, significantly associated with poor prognosis and are important provoking factors of TAMs. [ABSTRACT FROM AUTHOR]

Purpose: The progression of ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) in humans is highly variable. To better understand the relationship between them, we performed a multi-omic characterization of co-occurring DCIS and IBC lesions in a cohort of individuals. Methods: Formalin-fixed paraffin-embedded tissue samples from 50 patients with co-occurring DCIS and IBC lesions were subjected to DNA-seq and whole transcriptome RNA-seq. Paired DCIS and IBC multi-omics profiles were then interrogated for DNA mutations, gene expression profiles and pathway analysis. Results: Most small variants and copy number variations were shared between co-occurring DCIS and IBC lesions, with IBC exhibiting on average a higher degree of additional mutations. However, 36% of co-occurring lesions shared no common mutations and 49% shared no common copy number variations. The most frequent genomic variants in both DCIS and IBC were PIK3CA, TP53, KMT2C, MAP3K1, GATA3 and SF3B1, with KMT2C being more frequent in DCIS and TP53 and MAP3K1 more frequent in IBC, though the numbers are too small for definitive conclusions. The most frequent copy number variations were seen in MCL1, CKSB1 and ERBB2. ERBB2 changes were not seen in IBC unless present in the corresponding DCIS. Transcriptional profiles were highly distinct between DCIS and IBC, with DCIS exhibiting upregulation of immune-related signatures, while IBC showed significant overexpression in genes and pathways associated with cell division and proliferation. Interestingly, DCIS and IBC exhibited significant differential expression of different components of extracellular matrix (ECM) formation and regulation, with DCIS showing overexpression of ECM-membrane interaction components while IBC showed upregulation of genes associated with fibronectin and invadopodia. Conclusion: While most co-occurring DCIS and IBC were mutationally similar and suggestive of a common clonal progenitor, transcriptionally the lesions are highly distinct, with IBC expressing key pathways that facilitate invasion and proliferation. These results are suggestive of additional levels of regulation, epigenetic or other, that facilitate the acquisition of invasive properties during tumor evolution. [ABSTRACT FROM AUTHOR]

Background: Early invasive ductal carcinoma (IDC) breast cancer often presents with a coexisting ductal carcinoma in situ (DCIS) component, while about 5 % of cases present with an extensive (>25 %) intraductal component (EIC). The impact of EIC on the genomic risk of recurrence is unclear. Methods: Patients with early hormone receptor-positive HER2neu-negative (HR + HER2-) IDC breast cancer and a known OncotypeDX Breast Recurrence Score® (RS) who underwent breast surgery at our institute were included. Using a rule-based text-analysis algorithm, we analyzed pathological reports and categorized patients into three groups: EIC, non-extensive DCIS (DCIS-L), and pure-IDC (NO-DCIS). Genomic risk was determined using OncotypeDX RS. Results: A total of 33 (4.6 %) EIC cases, 377 (57.2 %) DCIS-L cases and 307 (42.8 %) NO-DCIS cases were identified. Patients in the EIC group were younger and had lower tumor grades than other groups. The distribution of genomic risk varied between the groups, with EIC tumors significantly less likely to have a high RS (>25) compared to DCIS-L and No-DCIS tumors (3 % vs 20 % and 20 %, respectively; p = 0.03). When adjusted to age, tumor size, grade and LNs involvement, both DCIS-L and NO-DCIS groups were significantly correlated with a higher probability of high RS compared to the EIC group (OR 12.3 and OR 13.1, respectively; p

Abstract Background Ductal Carcinoma In Situ (DCIS) can progress to invasive breast cancer, but most DCIS lesions never will. Therefore, four clinical trials (COMET, LORIS, LORETTA, AND LORD) test whether active surveillance for women with low-risk Ductal carcinoma In Situ is safe (E. S. Hwang et al., BMJ Open, 9: e026797, 2019, A. Francis et al., Eur J Cancer. 51: 2296–2303, 2015, Chizuko Kanbayashi et al. The international collaboration of active surveillance trials for low-risk DCIS (LORIS, LORD, COMET, LORETTA), L. E. Elshof et al., Eur J Cancer, 51, 1497–510, 2015). Low-risk is defined as grade I or II DCIS. Because DCIS grade is a major eligibility criteria in these trials, it would be very helpful to assess DCIS grade on mammography, informed by grade assessed on DCIS histopathology in pre-surgery biopsies, since surgery will not be performed on a significant number of patients participating in these trials. Objective To assess the performance and clinical utility of a convolutional neural network (CNN) in discriminating high-risk (grade III) DCIS and/or Invasive Breast Cancer (IBC) from low-risk (grade I/II) DCIS based on mammographic features. We explored whether the CNN could be used as a decision support tool, from excluding high-risk patients for active surveillance. Methods In this single centre retrospective study, 464 patients diagnosed with DCIS based on pre-surgery biopsy between 2000 and 2014 were included. The collection of mammography images was partitioned on a patient-level into two subsets, one for training containing 80% of cases (371 cases, 681 images) and 20% (93 cases, 173 images) for testing. A deep learning model based on the U-Net CNN was trained and validated on 681 two-dimensional mammograms. Classification performance was assessed with the Area Under the Curve (AUC) receiver operating characteristic and predictive values on the test set for predicting high risk DCIS-and high-risk DCIS and/ or IBC from low-risk DCIS. Results When classifying DCIS as high-risk, the deep learning network achieved a Positive Predictive Value (PPV) of 0.40, Negative Predictive Value (NPV) of 0.91 and an AUC of 0.72 on the test dataset. For distinguishing high-risk and/or upstaged DCIS (occult invasive breast cancer) from low-risk DCIS a PPV of 0.80, a NPV of 0.84 and an AUC of 0.76 were achieved. Conclusion For both scenarios (DCIS grade I/II vs. III, DCIS grade I/II vs. III and/or IBC) AUCs were high, 0.72 and 0.76, respectively, concluding that our convolutional neural network can discriminate low-grade from high-grade DCIS.

Background: 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. Methods: 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. Results: 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. Conclusions: 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. There is concern about overdiagnosis and overtreatment of ductal carcinoma in situ, the most common form of noninvasive breast cancer, because it is associated with an excellent prognosis. Nonclinical factors, including practice structure and geography, are associated with the receipt of surgery with radiation therapy and of mastectomy. [ABSTRACT FROM AUTHOR]

Ligands of the natural killer group 2D (NKG2DL) family are expressed on malignant cells and are usually absent from healthy tissues. Recognition of NKG2DLs such as MICA/B and ULBP1-3 by the activating immunoreceptor NKG2D, expressed by NK and cytotoxic T cells, stimulates anti-tumor immunity in breast cancer. Upregulation of membrane-bound NKG2DLs in breast cancer has been demonstrated by immunohistochemistry. Tumor cells release NKG2DLs via proteolytic cleavage as soluble (s)NKG2DLs, which allows for effective immune escape and is associated with poor prognosis. In this study, we collected serum from 140 breast cancer (BC) and 20 ductal carcinoma in situ (DCIS) patients at the time of initial diagnosis and 20 healthy volunteers (HVs). Serum levels of sNKG2DLs were quantified through the use of ELISA and correlated with clinical data. The analyzed sNKG2DLs were low to absent in HVs and significantly higher in BC patients. For some of the ligands analyzed, higher sNKG2DLs serum levels were associated with the classification of malignant tumor (TNM) stage and grading. Low sMICA serum levels were associated with significantly longer progression-free (PFS) and overall survival (OS). In conclusion, we provide the first insights into sNKG2DLs in BC patients and suggest their potential role in tumor immune escape in breast cancer. Furthermore, our observations suggest that serum sMICA levels may serve as a prognostic parameter in the patients analyzed in this study. [ABSTRACT FROM AUTHOR]

Relevance. Breast carcinomas (BC) remain one of the most actual problems of modern oncology. According to statistics, the incidence of BC is steadily increasing, making it the most common cancer pathology among women. In this situation, the aspect of diagnosing BC at early, non-invasive stages, is certainly important, which still reduces mortality, increases the possibility of organ-preserving treatment, duration and quality of life of patients.The purpose of study. The purpose of study is to investigate and perform a comparative analysis of imaging techniques for the diagnosis of non-invasive breast carcinomas.Materials and methods. Modern Russian and foreign literature about the diagnosis of non-invasive breast carcinomas was analyzed. Publications not older than 7 years published in specialized medical editions were taken into account Results. Not only main, but also new, promising imaging modalities that are not currently part of routine practice were analyzed. The main imaging patterns in non-invasive breast carcinomas (DCIS, LCIS and Paget's breast cancer), feasibility and prognostic value of certain diagnostic methods in different nosologies of this disease were also discussed.Conclusion. The statistics provided explain the importance of breast carcinomas problem, as well as the relevance of its diagnosis at non-invasive stages. According to the authors, the issue of accurate diagnosis of breast cancer in situ is subject to further discussion and study, but we would like to note that when non-invasive breast carcinoma is suspected and doubtful imaging results are obtained, one should not limit oneself only to routine methods of imaging studies, but expand further diagnostic tactics until accurate results are obtained and a final diagnosis is made.

Abstract Background CA15-3 is often elevated in breast cancer recurrence and rarely in ductal carcinoma in situ (DCIS). We report a case of DCIS with elevated CA15-3 levels, which was diagnosed after over 2 years of follow-up. Case presentation A 74-year-old woman presented with a left-sided breast mass and pain. Redness, swelling, and induration were observed in the left breast. Ultrasonography revealed a non-mass lesion in the left 3 o'clock position, skin thickening, and axillary lymphadenopathy. Serum CA15-3 levels were markedly high at 640 U/mL, suggesting inflammatory breast cancer. However, biopsies showed no malignancy. We diagnosed chronic mastitis with elevated CA15-3 levels and followed up with magnetic resonance imaging and a biopsy, as needed. Finally, DCIS was diagnosed 27 months after the first visit. She underwent a left mastectomy and a sentinel lymph node biopsy; DCIS had spread 6.5 cm and was immunohistochemically positive for CA15-3. No metastasis was found in the lymph nodes, but incidental Hodgkin lymphoma was observed. Postoperative normalization of CA15-3 levels indicated that she had DCIS with elevated CA15-3 levels. The patient underwent chemotherapy for Hodgkin lymphoma postoperatively, and there was no evidence of recurrence 1 year after surgery. Conclusion High CA15-3 levels can also be observed in DCIS, indicating that CA15-3 should not be used solely in breast cancer staging.

Background: The clinical outcome of breast carcinoma varies in each individual due to its molecular heterogeneity. There is a rising interest in whether the associated ductal carcinoma in-situ in invasive ductal carcinoma of breast affects the prognosis and overall survival of the patient. This study evaluates the difference in clinico-pathological and immunohistochemical prognostic factors between invasive ductal carcinoma with associated in-situ component, and invasive ductal carcinoma alone. Materials and Methods: The study was conducted at a tertiary care hospital in South Tamilnadu, India. Two study groups were categorized based on the presence/absence of in-situ component in invasive ductal carcinoma of breast. Clinico-pathological variables and immunohistochemistry [Estrogen receptor (ER), Progesterone receptor (PR), HER2/neu and ki67] findings were compared between the two groups and statistical analysis was performed. Results: There were 25 cases in each group. A significant statistical difference in tumor size was observed between invasive ductal carcinoma associated with in-situ component (mean-3.6cm) and without in-situ component (mean-5.0cm). A higher proliferative index (60%) was seen in invasive ductal carcinoma alone. There was no difference in the expression of Her2neu between the two groups. A proportionate increase in premenopausal population (60%) and hormone receptor positivity (ER, PR) was observed in invasive ductal carcinoma associated with in-situ component. Conclusions: Invasive ductal carcinoma associated with ductal carcinoma in-situ shows a less aggressive behaviour compared to invasive carcinoma alone. Further studies of a larger scale need to be done which might help in identifying the subgroup for targeted therapy.

Simple Summary: Ductal carcinoma in situ is a malignant cell proliferation confined to basement membrane. Current consensus guidelines recommend an optimal margin width of 2 mm and re-excision for closer margin is debated and it is sent back to clinical judgment. Our retrospective study evaluating 197 patients aim to investigate the importance of surgical margin and locoregional recurrence in patients with diagnosis of DCIS and treated with conservative breast surgery. We found no correlation between margins and loco-regional recurrence, and re-excision should be avoided in patients with focally positive margin and no evidence of the disease at post-surgical imaging. The current surgical guidelines recommend an optimal margin width of 2 mm for the management of patients diagnosed with ductal carcinoma in situ (DCIS). However, there are still many controversies regarding re-excision when the optimal margin criteria are not met in the first resection. The purpose of this study is to understand the importance of surgical margin width, re-excision, and treatments to avoid additional surgery on locoregional recurrence (LRR). The study is retrospective and analyzed surgical margins, adjuvant treatments, re-excision, and LRR in patients with DCIS who underwent breast-conserving surgery (BCS). A total of 197 patients were enrolled. Re-operation for a close margin rate was 13.5%, and the 3-year recurrence was 7.6%. No difference in the LRR was reported among the patients subjected to BCS regardless of the margin width (p = 0.295). The recurrence rate according to margin status was not significant (p = 0.484). Approximately 36.9% (n: 79) patients had resection margins < 2 mm. A sub-analysis of patients with margins < 2 mm showed no difference in the recurrence between the patients treated with a second surgery and those treated with radiation (p = 0.091). The recurrence rate according to margin status in patients with margins < 2 mm was not significant (p = 0.161). The margin was not a predictive factor of LRR p = 0.999. Surgical re-excision should be avoided in patients with a focally positive margin and no evidence of the disease at post-surgical imaging. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusion: The use of superparamagnetic iron oxide dye can prevent unnecessary axillary surgery in patients with DCIS undergoing mastectomy. [ABSTRACT FROM AUTHOR]

Introduction: The partial estrogen-agonist action of tamoxifen on bone receptors has beneficial effects on bone mineral density. However, in premenopausal women, the use of tamoxifen causes systemic estrogen depletion, which has detrimental effects on bone health. We aim to investigate the association between tamoxifen and osteoporosis in the real world using data from a longitudinal nationwide cohort of Korean patients. Methods: Data were collected from the National Health Insurance claims database in South Korea. Osteoporosis was defined by diagnostic codes accompanying prescription data for osteoporosis. The cumulative incidence was analyzed by Kaplan-Meier survival curves and the risk factors were analyzed using a multivariable Cox proportional hazard regression model. Results: Between 2009 and 2015, of the 4,654 women with ductal carcinoma in situ (DCIS) without prior osteoporosis, 2,970 were prescribed tamoxifen and 1,684 were not. A total of 356 DCIS survivors were later diagnosed with osteoporosis during a median follow-up period of 84 months. In the overall population, tamoxifen was associated with a low risk of osteoporosis, before and after propensity matching adjusted for age, operation type, and comorbidities (before matching, hazard ratio [HR]=0.69, 95% confidence interval [CI]=0.559-0.851, p<0.001; after matching, HR=0.664, 95% CI=0.513-0.858, p=0.002). In the subgroup analysis, findings were consistent in postmenopausal women but were not evident in the younger age group. Conclusion: In a nationwide cohort study, a low risk of osteoporosis was associated with the use of tamoxifen. The protective effect of tamoxifen was more profound in older women and was not related to the incidence of osteoporosis in younger women. [ABSTRACT FROM AUTHOR]

Background: CA15-3 is often elevated in breast cancer recurrence and rarely in ductal carcinoma in situ (DCIS). We report a case of DCIS with elevated CA15-3 levels, which was diagnosed after over 2 years of follow-up. Case presentation: A 74-year-old woman presented with a left-sided breast mass and pain. Redness, swelling, and induration were observed in the left breast. Ultrasonography revealed a non-mass lesion in the left 3 o'clock position, skin thickening, and axillary lymphadenopathy. Serum CA15-3 levels were markedly high at 640 U/mL, suggesting inflammatory breast cancer. However, biopsies showed no malignancy. We diagnosed chronic mastitis with elevated CA15-3 levels and followed up with magnetic resonance imaging and a biopsy, as needed. Finally, DCIS was diagnosed 27 months after the first visit. She underwent a left mastectomy and a sentinel lymph node biopsy; DCIS had spread 6.5 cm and was immunohistochemically positive for CA15-3. No metastasis was found in the lymph nodes, but incidental Hodgkin lymphoma was observed. Postoperative normalization of CA15-3 levels indicated that she had DCIS with elevated CA15-3 levels. The patient underwent chemotherapy for Hodgkin lymphoma postoperatively, and there was no evidence of recurrence 1 year after surgery. Conclusion: High CA15-3 levels can also be observed in DCIS, indicating that CA15-3 should not be used solely in breast cancer staging. [ABSTRACT FROM AUTHOR]

Abstract Background 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. Methods 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. Results 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. Conclusions 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. Trial registration ISRCTN27544579, prospectively registered on 22 May 2014

We report 2 rare cases of male breast cancer with bloody nipple discharge. Patient 1, a 32-year-old male, presented with a bloody nipple discharge from the left breast. Diagnostic workup revealed papillary ductal carcinoma in situ. Patient 1 underwent bilateral mastectomy with left axillary sentinel lymph node biopsy and has been doing well ever since. Patient 2, a 70-year-old male with concomitant metastatic prostate cancer, presented with a palpable right breast mass and with initially serous, then bloody nipple discharge. Diagnostic workup revealed invasive ductal carcinoma with ductal carcinoma in situ of the right breast. Patient 2 received aromatase inhibitor therapy prior to right total mastectomy with SLN biopsy followed by adjuvant tamoxifen therapy. Patient 2 recovered without complication for 2 years until metastatic disease recurrence was detected. This case report's purpose is to increase awareness and enhance understanding of the presentation, diagnosis, treatment, and outcomes of rare malignant pathologies.

Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce the risk of local recurrence (LR), including invasive LR, which carries a subsequent risk of breast cancer mortality. However, reliable and accurate individual risk prediction remains elusive and RT continues to be standardly recommended for most women with DCIS. Three molecular biomarkers have been studied to better estimate LR risk after BCS—Oncotype DX DCIS score, DCISionRT Decision Score and its associated Residual Risk subtypes, and Oncotype 21-gene Recurrence Score. All these molecular biomarkers represent important efforts towards improving predicted risk of LR after BCS. To prove clinical utility, these biomarkers require careful predictive modeling with calibration and external validation, and evidence of benefit to patients; on this front, further research is needed. Most trials do not incorporate molecular biomarkers in evaluating de-escalation of therapy for DCIS; however, one—the Prospective Evaluation of Breast-Conserving Surgery Alone in Low-Risk DCIS (ELISA) trial—incorporates the Oncotype DX DCIS score in defining a low-risk population and is an important next step in this line of research.

Myofibroblastoma (MFB) of the breast is a rare benign neoplasm of the mammary stroma. Several morphologic variants have been described in the literature, which can create diagnostic challenges for pathologists, in particular the epithelioid variant of MFB, which can mimic invasive lobular carcinoma. We report a case of a 72-year-old female who presented for a painless breast lump and was later found to have 2 lesions on imaging, with 1 lesion corresponding to the palpable lump and the other lying in a different quadrant. Core-needle biopsies demonstrated ductal carcinoma in-situ at both lesional sites with what was originally felt to be an invasive lobular carcinoma at the lesional site which did not correspond to the palpable lump. After mastectomy, with more complete visualization microscopically of the lesional area originally felt to be an invasive lobular carcinoma, the final pathology was consistent with a MFB, predominantly epithelioid variant, in addition to ductal carcinoma in-situ and lobular carcinoma in-situ. In this paper we describe the imaging findings of an epithelioid MFB and how its nonspecific nature necessitates close communication between the radiologist and pathologist to make the correct diagnosis.

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Trial registration: ISRCTN27544579, prospectively registered on 22 May 2014 [ABSTRACT FROM AUTHOR]

Background/aims: To investigate the diagnostic performance of breast MRI in revealing mammographically and sonographically occult lesions requiring excision in patients with pathologic nipple discharge. Materials and methods: In this retrospective study, 57 women with pathologic nipple discharge who had normal or inconclusive mammography and ultrasonography results and underwent breast MRI were determined. Patients who had histopathological diagnosis or ≥ 1-year imaging follow-up were included. MRIs were classified as positive and negative according to final BI-RADS assessment categories. Diagnostic performance of MRI, including sensitivity, specificity, negative predictive value, and positive predictive value, was calculated for detecting both malignancy and lesions requiring surgery. Results: Abnormal contrast enhancement on the pathologic nipple discharge side was detected in 29 MRIs (50.8%), categorized as BI-RADS 4. Abnormal findings were solid masses in 17 cases (58.6%) and non-mass enhancement in 12 cases (41.3%). Despite normal conventional imaging results, 4 malignant lesions and 16 lesions requiring surgery were detected with MRI. The sensitivity and specificity of MRI for detecting lesions requiring surgery were 100% and 68.2%, respectively. The positive predictive value (PPV) and negative predictive value were 55.1% and 100%, respectively. Conclusion: In conclusion, this study confirmed that MRI is a reliable tool to detect lesions requiring surgery in patients with pathologic nipple discharge. MRI should be used in routine workup in patients with normal conventional imaging and imaging follow-up can be safely applied in patients with negative MRI. [ABSTRACT FROM AUTHOR]

Background: Sector resection for Ductal Carcinoma in Situ (DCIS) allows wide excision without compromising breast shape. There are concerns that radiotherapy for some DCIS after sector resection is unnecessary and reduces patient satisfaction and quality of life without affecting survival. This study aimed to investigate whether women with DCIS managed with sector resection without radiotherapy had acceptable rates of recurrence and health‐related quality of life outcomes. Methods: Retrospective study of patients who underwent sector resection for DCIS without adjuvant radiotherapy from 1992 to 2021. Tumour size, grade, necrosis, margins, follow up and time to ipsilateral recurrence was recorded. Patients were posted a BREAST‐Q to assess health‐related quality of life. Results: One hundred and thirty‐eight patients were treated for pure DCIS by two surgeons from 1992 to 2018. One hundred and sixteen patients underwent sector resection, 22 had mastectomy. Average age 61 years. Mean follow up 9.14 years. Recurrence rate after sector resection was 18.97%. 55% were DCIS. Annualized recurrence rate was 2.07%. There were no cancer‐related deaths. BREAST‐Q completion rate was 44%. Satisfaction with breasts, physical, psychosocial, and sexual well‐being scores were significantly higher than normative Australian values and a mixed cohort of women who underwent breast conserving surgery with radiotherapy. Conclusion: DCIS can be safely managed with sector resection without radiotherapy and regular long‐term follow up. This approach results in low annualized recurrence rates, high levels patient satisfaction and health‐related quality of life and should be considered a safe alternative for patients with DCIS to minimize morbidity without affecting cancer survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Ductal carcinoma in situ (DCIS) is recognised as a precursor to invasive breast cancer (IBC), while lobular carcinoma in situ (LCIS) is considered a risk factor for subsequent IBC. To investigate whether the factors that increase the risks of DCIS and LCIS also predispose to IBC, we analysed risk factors for 3075 DCIS cases, 338 LCIS cases, and 1584 controls aged 35–60. Results showed that breastfeeding after childbirth decreased risks of DCIS and LCIS, similar to the association with IBC. Post-menopausal hormone replacement therapy (HRT) increased the risks of DCIS and LCIS, especially in long-term use (10+ years), with a stronger association with LCIS. However, neither parity nor an increasing number of births decreased the risks of DCIS or LCIS, as they do IBC. The study shows both similarities and differences in the risk factors affecting in situ breast cancer and IBC, and results suggest that regular surveillance is warranted in post-menopausal women taking long-term HRT. Ductal carcinoma in situ (DCIS) is widely accepted as a precursor of invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) is considered a risk factor for invasive lobular carcinoma (ILC), and it is unclear whether LCIS is also a precursor. Therefore, it would be expected that similar risk factors predispose to both DCIS and IDC, but not necessarily LCIS and ILC. This study examined associations with risk factors using data from 3075 DCIS cases, 338 LCIS cases, and 1584 controls aged 35–60, recruited from the UK-based GLACIER and ICICLE case-control studies between 2007 and 2012. Analysis showed that breastfeeding in parous women was protective against DCIS and LCIS, which is consistent with research on invasive breast cancer (IBC). Additionally, long-term use of HRT in post-menopausal women increased the risk of DCIS and LCIS, with a stronger association in LCIS, similar to the association with ILC. Contrary to findings with IBC, parity and the number of births were not protective against DCIS or LCIS, while oral contraceptives showed an unexpected protective effect. These findings suggest both similarities and differences in risk factors for DCIS and LCIS compared to IBC and that there may be justification for increased breast surveillance in post-menopausal women taking long-term HRT. [ABSTRACT FROM AUTHOR]

Adjuvant radiotherapy (RT) after breast-conserving surgery for DCIS lowers the relative local recurrence risk by half. To identify a low-risk group with the minimal benefit of RT could avoid side effects and spare costs. In this study, the outcome was compared for different RT-strategies using data from the randomized SweDCIS trial. Five strategies were compared in a Swedish setting: RT-to-none or all, RT to high-risk women defined by DCISionRT, modified Radiation Therapy Oncology Group (RTOG) 9804 criteria, and Swedish Guidelines. Ten-year recurrence risks and cost including adjuvant RT and local recurrence treatment cost were calculated. The mean age at recurrence was 64.4 years (36–90) and the mean cost for treating a recurrence was $21,104. In the SweDCIS cohort (n = 504), 59 women developed DCIS, and 31 invasive recurrence. Ten-year absolute local recurrence risk (invasive and DCIS) according to different strategies varied between 18.6% (12.5–23.6%) and 7.8% (5.0–12.6%) for RT-to-none or to-all, with an additional cost of $2614 US dollars per women and $24,201 per prevented recurrence for RT-to-all. The risk differences between other strategies were not statistically significant, but the larger proportion receiving RT, the fewer recurrences. DCISionRT spared 48% from RT with 8.1% less recurrences compared to RT-to-none, and a cost of $10,534 per prevented recurrence with additional cost depending on the price of the test. RTOG 9804 spared 39% from RT, with 9.7% less recurrences, $9525 per prevented recurrence and Swedish Guidelines spared 13% from RT, with 10.0% less recurrences, and $21,521 per prevented recurrence. It seems reasonable to omit RT in pre-specified low-risk groups with minimal effect on recurrence risk. Costs per prevented recurrence varied more than two-fold but which strategy that could be considered most cost-effective needs to be further evaluated, including the DCISionRT-test price. [ABSTRACT FROM AUTHOR]

Purpose of Review: This study summarizes the management and outcomes of ductal carcinoma in situ (DCIS). It will review recent literature including data supporting the use of a radiation boost, partial breast irradiation, endocrine therapy, HER2 therapy, genomic assays, and omission of radiation or surgery. Recent Findings: Evidence suggests there are a cohort of patients who may benefit from either tumor bed boost, partial breast irradiation, or omission of radiation. Summary: The management for DCIS is continuously evolving in order to identify patients who have higher risk features that necessitate aggressive treatment and those with more favorable features in whom we can de-escalate treatment. [ABSTRACT FROM AUTHOR]

Breast ductal carcinoma in situ (DCIS) is a preinvasive lesion that is considered to be a precursor to invasive breast cancer. Nevertheless, not all DCIS will progress to invasion. Current histopathological classification systems are unable to predict which cases will or will not progress, and therefore many women with DCIS may be overtreated. Artificial intelligence (AI) image-based analysis methods have potential to identify and analyze novel features that may facilitate tumor identification, prediction of disease outcome and response to treatment. Indeed, these methods prove promising for accurately identifying DCIS lesions, and show potential clinical utility in the therapeutic stratification of DCIS patients. Here, we review how AI techniques in histopathology may aid diagnosis and clinical decisions in regards to DCIS, and how such techniques could be incorporated into clinical practice.

INTRODUCTION: We previously developed a convolutional neural networks (CNN)-based algorithm to distinguish atypical ductal hyperplasia (ADH) from ductal carcinoma in situ (DCIS) using a mammographic dataset. The purpose of this study is to further validate our CNN algorithm by prospectively analyzing an unseen new dataset to evaluate the diagnostic performance of our algorithm. MATERIALS AND METHODS: In this institutional review board-approved study, a new dataset composed of 280 unique mammographic images from 140 patients was used to test our CNN algorithm. All patients underwent stereotactic-guided biopsy of calcifications and underwent surgical excision with available final pathology. The ADH group consisted of 122 images from 61 patients with the highest pathology diagnosis of ADH. The DCIS group consisted of 158 images from 79 patients with the highest pathology diagnosis of DCIS. Two standard mammographic magnification views (craniocaudal and mediolateral/lateromedial) of the calcifications were used for analysis. Calcifications were segmented using an open source software platform 3D slicer and resized to fit a 128 × 128 pixel bounding box. Our previously developed CNN algorithm was used. Briefly, a 15 hidden layer topology was used. The network architecture contained 5 residual layers and dropout of 0.25 after each convolution. Diagnostic performance metrics were analyzed including sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve. The positive class was defined as the pure ADH group in this study and thus specificity represents minimizing the amount of falsely labeled pure ADH cases. RESULTS: Area under the receiver operating characteristic curve was 0.90 (95% confidence interval, ± 0.04). Diagnostic accuracy, sensitivity, and specificity was 80.7%, 63.9%, and 93.7%, respectively. CONCLUSION: Prospectively tested on new unseen data, our CNN algorithm distinguished pure ADH from DCIS using mammographic images with high specificity.

BackgroundNovel biomarkers are required to discern between breast tumors that should be targeted for treatment from those that would never become clinically apparent and/or life threatening for patients. Moreover, therapeutics that specifically target breast cancer (BC) cells with tumor-initiating capacity to prevent recurrence are an unmet need. We investigated the clinical importance of LGR5 in BC and ductal carcinoma in situ (DCIS) to explore LGR5 as a biomarker and a therapeutic target.MethodsWe stained BC (n = 401) and DCIS (n = 119) tissue microarrays with an antibody against LGR5. We examined an LGR5 knockdown ER- cell line that was orthotopically transplanted and used for in vitro colony assays. We also determined the tumor-initiating role of Lgr5 in lineage-tracing experiments. Lastly, we transplanted ER- patient-derived xenografts into mice that were subsequently treated with a LGR5 antibody drug conjugate (anti-LGR5-ADC).ResultsLGR5 expression correlated with small tumor size, lower grade, lymph node negativity, and ER-positivity. ER+ patients with LGR5high tumors rarely had recurrence, while high-grade ER- patients with LGR5high expression recurred and died due to BC more often. Intriguingly, all the DCIS patients who later died of BC had LGR5-positive tumors. Colony assays and xenograft experiments substantiated a role for LGR5 in ER- tumor initiation and subsequent growth, which was further validated by lineage-tracing experiments in ER- /triple-negative BC mouse models. Importantly, by utilizing LGR5high patient-derived xenografts, we showed that anti-LGR5-ADC should be considered as a therapeutic for high-grade ER- BC.ConclusionLGR5 has distinct roles in ER- vs. ER+ BC with potential clinical applicability as a biomarker to identify patients in need of therapy and could serve as a therapeutic target for high-grade ER- BC.

Ligands of the natural killer group 2D (NKG2DL) family are expressed on malignant cells and are usually absent from healthy tissues. Recognition of NKG2DLs such as MICA/B and ULBP1-3 by the activating immunoreceptor NKG2D, expressed by NK and cytotoxic T cells, stimulates anti-tumor immunity in breast cancer. Upregulation of membrane-bound NKG2DLs in breast cancer has been demonstrated by immunohistochemistry. Tumor cells release NKG2DLs via proteolytic cleavage as soluble (s)NKG2DLs, which allows for effective immune escape and is associated with poor prognosis. In this study, we collected serum from 140 breast cancer (BC) and 20 ductal carcinoma in situ (DCIS) patients at the time of initial diagnosis and 20 healthy volunteers (HVs). Serum levels of sNKG2DLs were quantified through the use of ELISA and correlated with clinical data. The analyzed sNKG2DLs were low to absent in HVs and significantly higher in BC patients. For some of the ligands analyzed, higher sNKG2DLs serum levels were associated with the classification of malignant tumor (TNM) stage and grading. Low sMICA serum levels were associated with significantly longer progression-free (PFS) and overall survival (OS). In conclusion, we provide the first insights into sNKG2DLs in BC patients and suggest their potential role in tumor immune escape in breast cancer. Furthermore, our observations suggest that serum sMICA levels may serve as a prognostic parameter in the patients analyzed in this study.

Objectives Stereotactic core needle biopsy (SCNB) is used in the diagnostic assessment of suspicious mammographic calcifications to rule out breast ductal carcinoma in situ (DCIS). With advances in imaging technology and increased biopsy tissue volume, the detection rate of calcifications and DCIS in SCNB is unclear. Methods This retrospective study included 916 consecutive SCNBs for calcifications performed on 893 patients in a 2-year period. Results We found the cancer detection rate was 27.1% (DCIS, 23.7%; invasive, 3.4%). The detection rate for calcifications was 74.8% with the standard 3 levels. Additional leveling of calcification-negative cases further increased the detection of both calcifications (to 99.4% of cases) and DCIS (to 32.9% of cases). Lobular neoplasia (LN) was diagnosed in 41 cases. Twenty-five (61.0%) cases of LN were incidental without associated calcification. Of 32 invasive carcinomas detected on SCNB, 87.5% were T1a or less, and calcifications were associated with atypical ductal hyperplasia/DCIS or LCIS. The common benign lesions associated with calcifications were fibrocystic change (32.5%), fibroadenomatous change (30.2%), and columnar cell change and hyperplasia (8.2%). Conclusions We determined the up-to-date detection rates of calcification and DCIS in SCNB, as well as the common benign and malignant breast lesions associated with calcifications. Additional levels significantly increase the detection rate when standard levels show only stromal or scant/absent calcifications. Lobular neoplasia is often an incidental finding in SCNB for calcifications. When calcifications are present with LN, they are commonly florid, pleomorphic LCIS, or with concurrent invasive carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. This study aimed to investigate the potential influence of Mi on survival and assess its correlations with clinicopathological parameters, prognosis and molecular markers. Methods: The number of Mi foci in a cohort of 66 DCIS-Mi cases was assessed from haematoxylin and eosin-stained sections. Disease-free survival, clinicopathological parameters and biomarker expression were correlated with the number of Mi foci. Results: Higher numbers of Mi foci were found in larger tumours (P = 0.031). Conclusion: Greater extent of DCIS is associated with multifocal Mi. [ABSTRACT FROM AUTHOR]

Ultrasound images of ductal carcinoma in situ (DCIS) show a wide range of variations from mass to non-mass lesions. This article describes the characteristics of ultrasound images of DCIS based on the BC-02 study conducted by The Japanese Association of Breast and Thyroid Sonology (JABTS). In the BC-02 study, ultrasound images of 705 DCIS cases were classified by imaging findings. The results showed that non-mass abnormalities accounted for 60% of all lesions and masses for 40%. Looking at each subclassification, hypoechoic areas in the mammary gland were the most common (50% of the total), followed by solid masses (31%), mixed masses (9%), and abnormalities of the ducts (8%). These four classifications accounted for 98% of the total. Echogenic foci without a hypoechoic area, architectural distortion, and clustered microcysts were very rare, accounting for about 1% of the total. The ultrasound images of DCIS were characterized by a wide range of variations from masses to non-masses abnormalities, with hypoechoic areas in the mammary gland being the most common, followed by solid masses. [ABSTRACT FROM AUTHOR]

Ductal carcinoma in situ (DCIS) is the preinvasive form of breast cancer (BC). It is disputed whether all cases of DCIS require extensive treatment as the overall risk of progression to BC is estimated at 40%. Therefore, the crucial objective for researchers is to identify DCIS with significant risk of transformation into BC. Dendritic cells (DC) are professional antigen presenting cells and as such play a pivotal role in the formation of immune cells that infiltrate in breast tumors. The aim of this study was to investigate the relationship between the density of DCs with different superficial antigens (CD1a, CD123, DC-LAMP, DC-SIGN) and various histopathological characteristics of DCIS. Our evaluation indicated that CD123+ and DC-LAMP+ cells were strongly associated with maximal tumor size, grading and neoductgenesis. Together with CD1a+ cells, they were negatively correlated with hormonal receptors expression. Furthermore, the number of DC-LAMP+ cells was higher in DCIS with comedo necrosis, ductal spread, lobular cancerization as well as comedo-type tumors, while CD1a+ cells were abundant in cases with Paget disease. We concluded that different subpopulations of DCs relate to various characteristics of DCIS. Of the superficial DCs markers, DC-LAMP seems particularly promising as a target for further research in this area. [ABSTRACT FROM AUTHOR]

In this paper we investigate an inverse problem of two parameter identification with free boundary conditions modeling ductal carcinoma in situ (DCIS). Based on the characteristics of the DCIS model, we present an inverse problem of ductal carcinoma in situ (IPDCIS) under the conditions of incisional biopsy measurements at two different moments. Compared with the data in other literatures, this kind of measurements are more feasible and easy to obtain. Moreover, the uniqueness solution to the IPDCIS is proved. The IPDCIS of simultaneously determining unknown parameter and boundary function is transformed into a optimization problem, which can be solved by particle swarm optimization (PSO) method. The numerical simulation results are included to demonstrate the validity of the method and accuracy of the formulation of the IPDCIS. According to the information of clinical incision biopsy, the mathematical model of incision diagnosis of tumor growth pattern is established, and the unknown coefficients in the model are determined based on the proposed mathematical model. [ABSTRACT FROM AUTHOR]

Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce the risk of local recurrence (LR), including invasive LR, which carries a subsequent risk of breast cancer mortality. However, reliable and accurate individual risk prediction remains elusive and RT continues to be standardly recommended for most women with DCIS. Three molecular biomarkers have been studied to better estimate LR risk after BCS—Oncotype DX DCIS score, DCISionRT Decision Score and its associated Residual Risk subtypes, and Oncotype 21-gene Recurrence Score. All these molecular biomarkers represent important efforts towards improving predicted risk of LR after BCS. To prove clinical utility, these biomarkers require careful predictive modeling with calibration and external validation, and evidence of benefit to patients; on this front, further research is needed. Most trials do not incorporate molecular biomarkers in evaluating de-escalation of therapy for DCIS; however, one—the Prospective Evaluation of Breast-Conserving Surgery Alone in Low-Risk DCIS (ELISA) trial—incorporates the Oncotype DX DCIS score in defining a low-risk population and is an important next step in this line of research. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether the presence of calcifications in specimens collected during stereotactic-guided vacuum-assisted breast biopsies (VABB) is sufficient to ascertain their adequacy for final diagnosis at pathology. Materials and methods: Digital breast tomosynthesis (DBT)-guided VABBs were performed on 74 patients with calcifications as target. Each biopsy consisted of the collection of 12 samplings with a 9-gauge needle. This technique was integrated with a real-time radiography system (IRRS) which allowed the operator to determine whether calcifications were included in the specimens at the end of each of the 12 tissue collections through the acquisition of a radiograph of every sampling. Calcified and non-calcified specimens were separately sent to pathology and evaluated. Results: A total of 888 specimens were retrieved, 471 containing calcifications and 417 without. In 105 (22.2%) samples out of 471 with calcifications cancer was detected, while the remaining 366 (77.7%) were non-cancerous. Out of 417 specimens without calcifications 56 (13.4%) were cancerous, whereas 361 (86.5%) were non-cancerous. Seven hundred and twenty-seven specimens out of all 888 were cancer-free (81.8%, 95%CI 79–84%). Conclusion: Although there is a statistical significative difference between calcified and non-calcified samples and the detection of cancer (p < 0.001), our study shows that the sole presence of calcifications in the specimens is not sufficient to determine their adequacy for final diagnosis at pathology because non-calcified samples can be cancerous and vice-versa. Ending biopsies when calcifications are first detected through IRRS could lead to false negative results. [ABSTRACT FROM AUTHOR]