Expression of immune-related genes and breast cancer recurrence in women with ductal carcinoma in situ.

BACKGROUND AND AIM: Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer with highly variable clinical behavior, but risk stratification is still challenging. We sought to identify immune-related gene expression signatures of pure DCIS associated with different risks of breast cancer recurrence. METHODS: A retrospective nested case-control study of 143 pure DCIS was performed including 70 women with subsequent ipsilateral breast event (IBE, in situ or invasive; cases) and 73 DCIS women with no IBE and matched for age, tumor size, treatment, hormone receptors/HER2 status, and follow-up time (controls). RNA was extracted from DCIS samples and subjected to next-generation sequencing gene expression analysis of 395 immune-related genes. Correlations between DCIS immune-related gene expression and IBE were analyzed using weighted Cox regression for nested case-control data. RESULTS: Eight immune-related genes were differentially expressed between cases and controls. MAGEA10 expression (present vs. absent) and high expression levels of IFNA17 and CBLB (Q4 vs. Q1) were observed more frequently in DCIS of women with subsequent IBE, mainly invasive (p-valueFDR < 0.05). Conversely, expression of IL3RA1, TAGAP, TNFAIP8, and high expression levels of CCL2 and LRP1 were associated with a lower risk of IBE (p-valueFDR < 0.05). CONCLUSION: This exploratory analysis of pure DCIS showed significant differences in immune-related gene expression profiles between women with and with no subsequent IBE, particularly as invasive IBE. These results, after additional validation, could improve risk stratification and management of DCIS patients.

Tools to Guide Radiation Oncologists in the Management of DCIS.

Similar to invasive breast cancer, ductal carcinoma in situ is also going through a phase of changes not only from a technical but also a conceptual standpoint. From prescribing radiotherapy to everyone to personalized approaches, including radiotherapy omission, there is still a lack of a comprehensive framework to guide radiation oncologists in decision making. Many pieces of the puzzle are finding their place as high-quality data mature and are disseminated, but very often, the interpretation of risk factors and the perception of risk remain very highly subjective. Sharing the therapeutic choice with patients requires effective communication for an understanding of risks and benefits, facilitating an informed decision that does not increase anxiety and concerns about prognosis. The purpose of this narrative review is to summarize the current state of knowledge to highlight the tools available to radiation oncologists for managing DCIS, with an outlook on future developments.

Systematic review and meta-analysis of prognostic characteristics for breast cancers in populations with digital versus film mammography indicate the transition may have increased both early detection and overdiagnosis.

OBJECTIVE: Film mammography has replaced digital mammography in breast screening programs globally. This led to a small increase in the rate of detection, but whether the detection of clinically important cancers increased is uncertain. We aimed to assess the impact on tumour characteristics of screen-detected and interval breast cancers. STUDY DESIGN AND SETTING: We searched seven databases from inception to 08 October 2023 for publications comparing film and digital mammography within the same population of asymptomatic women at population (average) risk of breast cancer. We recorded reported tumour characteristics and assessed risk of bias using the ROBINS-I tool. We synthesized results using meta-analyses of random effects. RESULTS: Eighteen studies were included in the analysis from 8 countries, including 11,592,225 screening examinations (8,117,781 film; 3,474,444 digital). There were no differences in tumour size, morphology, grade, node status, receptor status, or stage in the pooled differences for screen-detected and interval invasive cancer tumour characteristics. There were statistically significant increases in screen-detected DCIS across all grades: 0.05 (0.00-0.11), 0.14 (0.05-0.22), and 0.19 (0.05-0.33) per 1,000 screens for low, intermediate, and high grade DCIS respectively. There were similar (non-statistically significant) increases in screen-detected invasive cancer across all grades. CONCLUSION: The increased detection of all grades of DCIS and invasive cancer may indicate both increased early detection of more aggressive disease and increased overdiagnosis. FUNDING: Australian National Health and Medical Research Council and the National Breast Cancer Foundation. REGISTRATION: PROSPERO 2017:CRD42017070601.

Nipple-Sparing Mastectomy and Adequate Margins for Patients With Ductal Carcinoma In Situ.

BACKGROUND: For patients with ductal carcinoma in situ (DCIS) undergoing breast conservation surgery (BCS), guidelines advise a margin width of at least 2 mm, with studies demonstrating decreased recurrence risk compared to narrower margins. However, limited data exist establishing if this margin is appropriate in mastectomies, and specifically for nipple-sparing mastectomy (NSM). Consequently, we evaluated the margins of DCIS patients undergoing NSM and resulting oncologic outcomes. METHODS: A single-institution retrospective review was performed in patients with DCIS or DCIS with microinvasion (DCIS + MI) undergoing NSM from April 2010 to December 2021. Patient and tumor characteristics, margin status, treatment, and outcomes information were collected. The association between margins and local-regional (LRR) and distant recurrence (DR) were examined. RESULTS: 161 patients were included, comprising 284 NSM (164 therapeutic, 120 prophylactic). 153 patients had DCIS and 8 had DCIS + MI. Most patients had hormone sensitive, 123 (76.4%), and nuclear grade 2, 72 (44.7%), disease. In total, 35 (21.7%) patients had positive or <2 mm margins. Of these, 21 (60%) involved the anterior margin. At a median follow-up of 45 months (range 0-151), 2.5% (n = 4) had a LRR and .6% (n = 1) had a DR. Of patients with a recurrence, only 2 had positive or <2 mm margins, 1 had received endocrine therapy, and none received adjuvant radiation. DISCUSSION: No specific margin status was found to correlate with recurrence for patients with DCIS or DCIS + MI undergoing NSM, with an altogether low recurrence risk. Overall, this suggests that recommended DCIS margins in BCS doesn't necessarily apply in NSM, where margins of <2 mm may be acceptable.

Assessing the malignancy of suspicious breast microcalcifications: the role of contrast enhanced mammography.

PURPOSE: To assess the role of contrast-enhanced mammography (CEM) in predicting the malignancy of breast calcifications. MATERIAL AND METHODS: We retrospectively evaluated patients with suspicious calcifications (BIRADS 4) who underwent CEM and stereotactic vacuum-assisted biopsy (VAB) at our institution. We assessed the sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of CEM in predicting malignancy of microcalcifications with a 95% confidence interval; we performed an overall analysis and a subgroup analysis stratified into group A-low risk (BIRADS 4a) and group B-medium/high risk (BIRADS 4b-4c). We then evaluated the correlation between enhancement and tumour proliferation index (Ki-67) for all malignant lesions. RESULTS: Data from 182 patients with 184 lesions were collected. Overall the SE of CEM in predicting the malignancy of microcalcifications was 0.70, SP was 0.85, the PPV was 0.82, the NPV was 0.76 and AUC was 0.78. SE in group A was 0.89, SP was 0.89, PPV was 0.57, NPV was 0.98 and AUC was 0.75. SE in group B was 0.68, SP was 0.80, PPV was 0.87, NPV was 0.57 and AUC was 0.75. Among malignant microcalcifications that showed enhancement (N = 52), 61.5% had Ki-67 ≥ 20% and 38.5% had low Ki-67 values. Among the lesions that did not show enhancement (N = 22), 90.9% had Ki-67 < 20% and 9.1% showed high Ki-67 values 20%. CONCLUSIONS: The absence of enhancement can be used as an indicative parameter for the absence of disease in cases of low-suspicious microcalcifications, but not in intermediate-high suspicious ones for which biopsy remains mandatory and can be used to distinguish indolent lesions from more aggressive neoplasms, with consequent reduction of overdiagnosis and overtreatment.

Ductal carcinoma in situ within a fibroadenoma: A case report and review of literature.

BACKGROUND: Fibroadenoma (FA) is the most common tumor found in young women, although it can occur in any age group. Ductal carcinoma in situ (DCIS) that is confined in a FA is rare; it is most frequently reported as an incidental finding. CASE SUMMARY: We report a case of DCIS within a FA in a 46-year-old female without cancer-related personal and family histories. The patient was diagnosed with a breast conglomerate of nodules and was followed for 1 year. In the current control image study, we found suspicious microcalcification, as a new finding, within one of the nodules. Consequently, a core biopsy of the tumor, which appeared hypoechoic, oval, and circumscribed, was performed. The pathological diagnosis was ductal carcinoma in situ within a fibroepithelial lesion. The patient underwent breast-conserving surgery and received radiotherapy as well as endocrine therapy (tamoxifen). CONCLUSION: We recommend a multidisciplinary approach for adequate treatment and follow-up.

Outcomes of atypical (B3) core biopsy lesions diagnosed across BreastScreen NSW, Australia.

INTRODUCTION: Atypical or B3 lesions comprise a heterogeneous group of uncertain malignant potential. B3 lesions diagnosed on core biopsy are usually recommended for diagnostic open biopsy. Identifying factors which could allow conservative management of B3 lesions would be helpful in avoiding unnecessary surgery. The aim of this study was to identify the upgrade rate to malignancy for B3 core biopsy lesions and to compare characteristics of lesions which were malignant and benign at excision. METHOD: This retrospective study used data from BreastScreen New South Wales (NSW), Australia, of women who were diagnosed with B3 lesions on needle biopsy from 2011 to 2019. RESULTS: During the study period, 1927 B3 lesions were included. The upgrade rate to malignancy was 26.4%. Of the malignant lesions on excision, 29.6% were invasive and 69.2% were in situ. The rates of upgrade to invasive cancer and DCIS varied substantially with the core biopsy lesion type. Lesions with atypia on core biopsy had significantly higher upgrade rates to malignancy at 34.7% compared to 13.6% for lesions without atypia (p < 0.0001). Lesions with malignant pathology were significantly larger than those with benign pathology (difference = 5.1 mm (95% CI 2.7-7.5 mm), p < 0.001). CONCLUSIONS: The overall upgrade rate of B3 lesions to malignancy was 26.4%. The majority of the lesions were upgraded to DCIS instead of invasive cancer. Upgrade rates varied by lesion type. Lesions with atypia had significantly higher upgrade rates to cancer compared to lesions without atypia. Malignant lesions were significantly larger than benign lesions.

High-grade pancreatic intraepithelial neoplasia diagnosed based on changes in magnetic resonance cholangiopancreatography findings: A case report.

BACKGROUND: High-grade pancreatic intraepithelial neoplasia (PanIN) exhibits no mass and is not detected by any examination modalities. However, it can be diagnosed by pancreatic juice cytology from indirect findings. Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct (MPD) and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography (ERCP). We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range, but without caudal MPD dilatation on magnetic resonance cholangiopancreatography (MRCP). CASE SUMMARY: A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision, which revealed pancreatic cysts. MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation. Thus, course observation was performed. After 24 mo, MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst. We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination. We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN. Pancreatic parenchyma invasion was not observed, and curative resection was achieved. CONCLUSION: High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.

Prevalence of diverse colorectal polyps and risk factors for colorectal carcinoma in situ and neoplastic polyps.

BACKGROUND: Most colorectal cancers originate from precancerous polyps. This study aimed to determine the prevalence of colorectal polyps with diverse pathological morphologies and to explore the risk factors for colorectal carcinoma in situ (CCS) and neoplastic polyps. METHODS: Inpatients admitted from January 2018 to May 2023 were screened through the hospital information system. Polyps were classified according to pathological morphology. The prevalence of polyps was described by frequency and 95% confidence interval. Univariate and multivariate logistic regression analyses were used to explore the risk factors for CCS and neoplastic polyps. RESULTS: In total, 2329 individuals with 3550 polyps were recruited. Among all patients, 76.99% had neoplastic polyps and 44.31% had advanced adenomas. Tubular adenoma had the highest prevalence at 60.15%, and the prevalence of CCS was 3.86%. Patients with a colorectal polyp diameter ≥ 1.0 cm or number ≥ 3 were 8.07 times or 1.98 times more likely to develop CCS than were those with a diameter < 1.0 cm or number < 3, respectively (OR 8.07, 95%CI 4.48-14.55, p < 0.0001; and OR 1.98, 95%CI 1.27-3.09, p = 0.002). The risk of CCS with schistosome egg deposition was also significantly increased (OR 2.70, 95%CI 1.05-6.98). The higher the levels of carbohydrate antigen (CA) 724 (OR 1.01, 95%CI 1.00-1.02) and CA211 (OR 1.16, 95%CI 1.03-1.32) in patients with colorectal polyps were, the greater the risk of CCS. When colorectal neoplastic polyps were analyzed, we discovered that for each 1-year increase in age, the risk of neoplastic polyps increased by 3% (OR 1.03, 95%CI 1.02-1.04), p < 0.0001. Patients with a polyp diameter ≥ 1.0 cm had a 2.11-fold greater risk of neoplastic polyps compared to diameter < 1.0 cm patients (OR 3.11, 95%CI 2.48-3.92), p < 0.0001. In addition, multiple polyps and CA199 levels are risk factors for neoplastic polyps. CONCLUSION: More than 3/4 of colorectal polyp patients have neoplastic polyps. Patients are more inclined to develop CCS and neoplastic polyps if they have large polyps (> 1.0 cm) or multifocal polyps. The levels of the tumor markers CA724 and CA211 show some potential usefulness for predicting CCS and may be exploited for early identification of high-risk populations.

Inhibiting Pathological Calcium Phosphate Mineralization: Implications for Disease Progression.

Pathological calcifications, especially calcium phosphate microcalcifications (MCs), appear in most early breast cancer lesions, and their formation correlates with more aggressive tumors and a poorer prognosis. Hydroxyapatite (HA) is a key MC component that crystallizes in the tumor microenvironment. It is often associated with malignant breast cancer lesions and can trigger tumorigenesis in vitro. Here, we investigate the impact of additives on HA crystallization and inhibition, and how precancerous breast cells respond to minerals that are deposited in the presence of these additives. We show that nonstoichiometric HA spontaneously crystallizes in a solution simulating the tumor microenvironmental fluids and exhibits lump-like morphology similar to breast cancer MCs. In this system, the effectiveness of poly(aspartic acid) and poly(acrylic acid) (PAA) to inhibit HA is examined as a potential route to improve cancer prognosis. In the presence of additives, the formation of HA lumps is associated with the promotion or only minimal inhibition of mineralization, whereas the formation of amorphous calcium phosphate (ACP) lumps is followed by inhibition of mineralization. PAA emerges as a robust HA inhibitor by forming spherical ACP particles. When precancerous breast cells are exposed to various HA and ACP minerals, the most influential factors on cell proliferation are the mineral phase and whether the mineral is in the form of discrete particles or particle aggregates. The tumorigenic effects on cells, ranging from cytotoxicity and suppression of proliferation to triggering of proliferation, can be summarized as HA particles < HA aggregates < ACP particles < ACP aggregates. The cellular response to minerals can be attributed to a combination of factors, including mineral phase, crystallinity, morphology, surface texture, aggregation state, and surface potential. These findings have implications for understanding mineral-cell interactions within the tumor microenvironment and suggest that, in some cases, the byproducts of HA inhibition can contribute to disease progression more than HA itself.

Paget's Presentation of High-Grade Ductal Carcinoma In Situ (DCIS) in a Very Young Female With Breast Cancer 2 (BRCA2) Mutation.

This is a case of a previously healthy 29-year-old female with erythema and skin excoriations of the left breast nipple-areolar complex (NAC). After a repeat trial and failure of topical hydrocortisone, a diagnostic mammogram and nipple biopsy revealed Paget's disease (PD) of the nipple with ductal carcinoma in situ (DCIS). A subsequent genetic analysis found a breast cancer 2 (BRCA2) gene mutation. Treatment consisted of a left breast skin-sparing simple mastectomy with sentinel lymph node (SLN) biopsy and immediate tissue expander placement for implant reconstruction. Further management involved right breast short-interval surveillance with annual mammography and magnetic resonance imaging (MRI) with the possibility of prophylactic surgery along with oophorectomy after childbearing.

Changing trends in the management of ductal carcinoma in situ in Republic of Korea: a comprehensive analysis using Health Insurance Review and Assessment data [2009-2020].

Background: Increasing rates of diagnosis of ductal carcinoma in situ (DCIS), given the widespread use of mammography, is a global trend. Various attempts have been made in the selection of surgical methods and application of radiation therapy (RT), and the prevalence of infectious diseases has also affected these attempts. This study aimed to investigate evolving treatment patterns and trends in the management of DCIS in South Korea. Methods: We conducted a comprehensive search of the Korean Health Insurance Review and Assessment Service-National Patient Sample (HIRA-NPS) database and selected patients who underwent breast surgery following a DCIS diagnosis between 2009 and 2020. Based on this sample, the analyses were weighted according to the Korean population. We examined annual variations in mastectomy types, reconstructive procedures, and RT utilization from a multidisciplinary perspective. Results: In our weighted sample, 43,780 patients with DCIS underwent surgery, with a consistent annual increase of 10%. The proportion of lumpectomy procedures increased from 56.7% to 65.4%, showing a greater growth rate than that of total mastectomies (TMs). Following the availability of reconstruction data in 2015, shifts have emerged toward a preference for implant-based autologous tissue reconstruction. As we transitioned to the latter part of our study, the trend was marked by the increasing adoption of hypofractionated RT and omission of RT. Of the patients who underwent lumpectomy in 2020, 25.6% adopted hypofractionated RT and 53.8% omitted RT. This transformation was particularly evident among older patients, individuals treated in metropolitan areas, and those treated in small-sized healthcare facilities. Conclusions: Our study sheds light on the changing landscape of DCIS treatment in South Korea incorporating perspectives from surgeons, plastic surgeons, and radiation oncologists. We observed an increase in the rates of lumpectomy and implant-based reconstruction. Adoption of hypofractionated RT and omission of RT showed increasing trends.

Immediate and delayed risk of breast cancer associated with classic lobular carcinoma in situ and its variants.

OBJECTIVE: To determine the risk of breast cancer due to lobular carcinoma in situ (LCIS). METHODS: This retrospective IRB-approved study identified cases of LCIS after percutaneous breast biopsy from 7/2005 to 7/2022. Excluded were cases with less than 2 years of imaging surveillance or a concurrent ipsilateral breast cancer diagnosis within 6 months of the LCIS diagnosis. Final outcomes of cancer versus no cancer were determined by pathology at surgical excision or the absence of cancer on imaging surveillance. RESULTS: A total of 116 LCIS lesions were identified. The primary imaging findings targeted for percutaneous biopsy included calcifications (50.0%, 58/116), MR enhancing lesions (25.0%, 29/116), noncalcified mammographic architectural distortions (10.3%, 12/116), or masses (14.7%, 17/116). Surgical excision was performed in 49.1% (57/116) and imaging surveillance was performed in 50.9% (59/116) of LCIS cases. There were 22 cancers of which 11 cancers were discovered at immediate excision [19.3% (11/57) immediate upgrade] and 11 cancers developed later while on imaging surveillance [18.6% (11/59) delayed risk for cancer]. Among all 22 cancers, 63.6% (14/22) occurred at the site of LCIS (11 at immediate excision and 3 at surveillance) and 36.4% (8/22) occurred at a location away from the site of LCIS (6 in a different quadrant and 2 in the contralateral breast). CONCLUSION: LCIS has both an immediate risk (19.3%) and a delayed risk (18.6%) for cancer with 90.9% occurring in the ipsilateral breast (63.6% at and 27.3% away from the site of LCIS) and 9.1% occurring in the contralateral breast.

Breast tissue imaging atlas using ultra-fast confocal microscopy to identify cancer lesions.

New generation ultra-fast fluorescence confocal microscopy (UFCM) allows to image histological architecture of fresh breast tissue and may be used for ex vivo intraoperative analysis for margin status. The criteria to identify breast tumoral and non-tumoral tissues in UFCM images are still objects of investigation. The objective of the study was to create an atlas of ex vivo UFCM images of breast tissues and breast carcinomas based on the first extensive collection of large field-of-view UFCM breast images. One hundred sixty patients who underwent conserving surgery for breast cancer were included. Their fresh surgical specimens were sliced, stained with acridine orange, and imaged at high resolution with large-field-of-view UFCM. The resulting images were digitally false colored to resemble frozen sections. Each UFCM image was correlated with the corresponding definitive histology. Representative images of normal tissue, inflammation, benign lesions, invasive carcinoma (IC), and ductal carcinoma in situ (DCIS) were collected. A total of 320 large-field images were recorded from 58 IC of no special type, 44 invasive lobular carcinomas, 1 invasive mucinous carcinoma, 47 DCIS, 2 lobular carcinomas in situ, and 8 specimens without cancer. Representative images of the main components of the normal breast and the main types of ICs and DCIS were annotated to establish an UFCM atlas. UFCM enables the imaging of the fresh breast tissue sections. Main morphological criteria defined in traditional histopathology such as tissue architecture and cell features can be applied to describe UFCM images content. The generated atlas of the main normal or tumoral tissue features will support the adoption of this optical technology for the intraoperative examination of breast specimens in clinical practice as it can be used to train physicians on UFCM images and develop artificial intelligence algorithms. Further studies are needed to document rare breast lesions.

Bowen disease with sebaceous differentiation arising from clonal seborrheic keratosis.

We present a rare case of clonal seborrheic keratosis (SK) with focal Bowen disease (BD) (squamous cell carcinoma in situ) accompanied by sebaceous differentiation. An 89-year-old woman presented with a pale reddish-brown plaque on the left buttock. Histopathological examination of the excisional specimen revealed hyperkeratosis, acanthosis, and intraepidermal epithelioma. In some areas of the tumor, we observed proliferation of basaloid keratinocytes within the intraepidermal nests and pseudohorn cysts. This area was diagnosed as clonal SK. However, in other areas, the tumor cells within the intraepidermal nests showed nuclear pleomorphism, abnormal mitoses, dyskeratotic cells, and clumping cells, consistent with BD with a nested/clonal pattern (clonal BD). The SK and BD areas were contiguous with the transitional zone. Some nests within the BD area contained vacuolated cells with bubbly cytoplasm and scalloped nuclei, suggestive of sebaceous differentiation. Therefore, we made the diagnosis of clonal BD with sebaceous differentiation arising from clonal SK. All areas contained intraepidermal nests, which revealed that the lesions were not the result of accidental collision, but that the neoplastic cells in the intraepidermal nests of the SK transformed into BD and underwent sebaceous differentiation.

Familial pancreatic cancer: a long fruitful journey.

In the early years of my GI fellowship, a healthy 40-year-old man came to my clinic and announced that he was going to die of pancreatic cancer. His brothers, father and uncles had all died of the disease; he felt his fate was inescapable. I asked whether his family members had seen doctors or had any tests. His answer was yes to both. Even so, doctors could not diagnose the pancreatic cancer at early stages. CT scans were always negative. I thought to myself, in order to help this patient-CT scans may not be reliable for early detection. Perhaps other methods of imaging the pancreas might be of more benefit. This patient opened a door that led to a 30-year journey of trying to detect pancreatic cancer at earlier stages when it is curable.

Upgrade Rates of Variant Lobular Carcinoma In Situ Compared to Classic Lobular Carcinoma In Situ Diagnosed in Core Needle Biopsies: A 10-Year Single Institution Retrospective Study.

The primary aim of this study was to determine the upgrade rates of variant lobular carcinoma in situ (V-LCIS, ie, combined florid [F-LCIS] and pleomorphic [P-LCIS]) compared with classic LCIS (C-LCIS) when diagnosed on core needle biopsy (CNB). The secondary goal was to determine the rate of progression/development of invasive carcinoma on long-term follow-up after primary excision. After institutional review board approval, our institutional pathology database was searched for patients with "pure" LCIS diagnosed on CNB who underwent subsequent excision. Radiologic findings were reviewed, radiologic-pathologic (rad-path) correlation was performed, and follow-up patient outcome data were obtained. One hundred twenty cases of LCIS were identified on CNB (C-LCIS = 97, F-LCIS = 18, and P-LCIS = 5). Overall upgrade rates after excision for C-LCIS, F-LCIS, and P-LCIS were 14% (14/97), 44% (8/18), and 40% (2/5), respectively. Of the total cases, 79 (66%) were deemed rad-path concordant. Of these, the upgrade rate after excision for C-LCIS, F-LCIS, and P-LCIS was 7.5% (5 of 66), 40% (4 of 10), and 0% (0 of 3), respectively. The overall upgrade rate for V-LCIS was higher than for C-LCIS (P = .004), even for the cases deemed rad-path concordant (P value: .036). Most upgraded cases (23 of 24) showed pT1a disease or lower. With an average follow-up of 83 months, invasive carcinoma in the ipsilateral breast was identified in 8/120 (7%) cases. Six patients had died: 2 of (contralateral) breast cancer and 4 of other causes. Because of a high upgrade rate, V-LCIS diagnosed on CNB should always be excised. The upgrade rate for C-LCIS (even when rad-path concordant) is higher than reported in many other studies. Rad-path concordance read, surgical consultation, and individualized decision making are recommended for C-LCIS cases. The risk of developing invasive carcinoma after LCIS diagnosis is small (7% with ∼7-year follow-up), but active surveillance is required to diagnose early-stage disease.

Development of erlotinib-loaded nanotransferosomal gel for the topical treatment of ductal carcinoma in situ.

Aims: This study was aimed to formulate erlotinib (ERL)-loaded transferosomal gel (ERL@TG) intended for topical application for the treatment of ductal carcinoma in situ. Materials & methods: The optimized process involved a thin-film hydration method to generate ERL-loaded transferosomes (ERL@TFS), which was incorporated into a carbopol gel matrix to generate ERL@TG. The optimized formulation was characterized in vitro followed by cytotoxicity evaluation on MCF-7 breast cancer cell lines and acute toxicity and skin irritation studies was performed in vivo. Results: In a comparative assessment against plain ERL, ERL@TG displayed enhanced efficacy against MCF-7 cell lines, reflected in considerably lower IC50 values with an enhanced safety profile. Conclusion: Optimized ERL@TG was identified as a promising avenue for addressing ductal carcinoma in situ breast cancer.

Despite progress, breast cancer remains a significant cause of death. This study aimed to revolutionize the treatment of noninvasive ductal carcinoma in situ, a type of breast cancer, by developing a special gel that can be applied directly to the breast. The developed gel was in the nanoform, a 'nanotransfersomal' gel that contained erlotinib, a potent drug for breast cancer. To ensure its effectiveness, we evaluated the erlotinib-loaded transfersomal gel through various tests. The results confirmed that the gel was nano-sized and loaded with a high amount of erlotinib. Animal studies were conducted to check if the prepared gel caused any skin irritation and interestingly, there was no irritation observed on the animals' skin. Furthermore, we treated breast cancer cells with the developed gel using a method called MTT assay and the results showed improved cell-killing activity in comparison to plain drug. In conclusion, this special gel represents a breakthrough in breast cancer treatment. It offers hope for better outcomes in the fight against this disease. This innovative approach involves directly applying the gel on the affected area topically to increase patient compliance and decreasing side effects of drugs. This could potentially transform ductal carcinoma in situ breast cancer treatment, bringing us closer to improved treatments and outcomes.

Exposure to di-2-ethylhexyl phthalate and breast neoplasm incidence: A cohort study.

BACKGROUND: Phthalates are ubiquitous environmental endocrine disruptors. As the predominant phthalate, di-2-ethylhexyl phthalate (DEHP) has been considered possibly carcinogenic to humans but large-scale longitudinal evidence is needed to further clarify its carcinogenicity. OBJECTIVES: To examine the association between DEHP exposure and incidence of breast malignant neoplasm, carcinoma in situ and benign neoplasm. METHODS: A total of 273,295 women from UK Biobank cohort were followed up for a median of 13.5 years. Disease information was collected from National Health Service Cancer Registry and National Death Index. Baseline and yearly-average level of DEHP exposure were estimated for each individual by linking chemical monitoring record of European Environment Agency with home address of the participants by Kriging interpolation model. Cox proportional hazard model was employed to estimate the association between DEHP exposure and breast neoplasms. RESULTS: The median (IQR) of baseline and yearly-average DEHP concentration were 8000.25 (interquartile range: 6657.85-11,948.83) and 8000.25 (interquartile range: 1819.93-11,359.55) µg/L. The highest quartile of baseline DEHP was associated with 1.11 fold risk of carcinoma in situ (95 % CI, 1.00, 1.23, p < 0.001) and 1.27 fold risk of benign neoplasm (95 % CI, 1.05, 1.54, p < 0.001). As for yearly-average exposure, each quartile of DEHP was positively associated with higher risk of malignant neoplasm (HR, 1.05; 95 % CI, 1.03, 1.07, p < 0.001), carcinoma in situ (HR, 1.08; 95 % CI, 1.04, 1.11, p < 0.001) and benign neoplasm (HR, 1.13; 95 % CI, 1.07, 1.20, p < 0.001). Stratification analysis showed no significant modification effects on the DEHP-neoplasm relationship by menopausal status or ethnicity but a suggestive higher risk in younger women and those who underwent oral contraceptive pill therapy. In sensitivity analysis, the associations remained when excluding the cases diagnosed within 2 years post baseline. CONCLUSIONS: Real-world level of DEHP exposure was associated with higher risk of breast neoplasms. Because of the health risks associated with DEHP, its release to the environment should be managed.