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The management of burn injuries presents a significant challenge in clinical settings, yet an optimal solution remains elusive. Therefore, this study aimed to develop a topical therapeutic formulation to address the complex issues hindering burn wound healing. Emphasizing the sustained presence of bioactive principles, we synthesized a bioactive gel derived from decellularized caprine small intestine submucosa (D-CIS) and encapsulated it with nano-formulations of cerium oxide and curcumin to create a burn wound dressing material with enhanced properties. The choice of encapsulated components was guided by their antimicrobial, antioxidant, and immune-modulating characteristics, along with their inherent ability to gradually release bioactive substances. The encapsulated (cerium oxide and curcumin) D-CIS bioactive gel demonstrated a range of properties, including antimicrobial, antioxidant, and anti-inflammatory effects, along with sustained release kinetics of bioactive molecules. These combined effects facilitated accelerated burn wound healing by mitigating oxidative stress, reducing inflammation, and promoting cell recruitment for epithelial and vascular regeneration. This study contributes to the development of a novel bioactive gel incorporating cerium oxide and curcumin, offering a promising approach to enhance burn wound healing.

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BACKGROUND/AIM: Ductal carcinoma in situ is considered a local disease with no metastatic potential, thus sentinel lymph node biopsy (SLNB) may be deemed an overtreatment. SLNB should be reserved for patients with invasive cancer, even though the risk of upstaging rises to 25 %. We aimed to identify clinicopathological predictors of post-operative upstaging in invasive carcinoma. METHODS: We retrospectively analyzed patients with a pre-operative diagnosis of DCIS subjected to breast surgery between January 2017 to December 2021, and evaluated at the Breast Unit of PTV (Policlinico Tor Vergata, Rome). RESULTS: Out of 267 patients diagnosed with DCIS, 33(12.4 %) received a diagnosis upstaging and 9(3.37 %) patients presented with sentinel lymph node (SLN) metastasis. In multivariate analysis, grade 3 tumor (OR 1.9; 95 % CI 1.2-5.6), dense nodule at mammography (OR 1.3; 95 % CI 1.1-2.6) and presence of a solid nodule at ultrasonography (OR 1.5; 95 % CI 1.2-2.6) were independent upstaging predictors. Differently, the independent predictors for SLNB metastasis were: upstaging (OR 2.1.; 95 % CI 1.2-4.6; p = 0.0079) and age between 40 and 60yrs (OR 1.4; 95 % CI 1.4-2.7; p = 0.027). All 9 patients with SLN metastasis received a diagnosis upstaging and were aged between 40 and 60 years old. CONCLUSION: We identified pre-operative independent predictors of upstaging to invasive ductal carcinoma. The combined use of different predictors in an algorithm for surgical treatments of DCIS could reduce the numbers of unnecessary SLNB.

Asunto(s)

Algoritmos , Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Metástasis Linfática , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Estudios Retrospectivos , Persona de Mediana Edad , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/secundario , Carcinoma Ductal de Mama/cirugía , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/secundario , Adulto , Anciano , Biopsia del Ganglio Linfático Centinela/métodos , Pronóstico , Estudios de Seguimiento , Mamografía , Mastectomía , Estadificación de Neoplasias

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

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BACKGROUND: Breast conserving surgery (BCS) is well established for the management of ductal carcinoma in situ (DCIS), but neither randomized trials nor guidelines address management of ipsilateral breast tumor recurrence (IBTR) after BCS for DCIS. PATIENTS AND METHODS: We identified women treated with BCS for DCIS who developed IBTR as a first event. Between those treated with mastectomy versus re-BCS, we compare the clinicopathologic characteristics, the use of adjuvant radiotherapy (RT) both upfront ("primary RT") and post IBTR ("secondary RT"), of tamoxifen, the rate of third events (local, regional, distant), and both breast cancer specific (BCSS) and overall survival (OS). RESULTS: Of 3001 women treated with BCS for DCIS (1978-2010), 383 developed an IBTR as a first event (1983-2023) and were treated by mastectomy (51%) versus re-BCS (49%). Compared with re-BCS, mastectomy patients at initial treatment were higher grade (74% versus 59%, p = 0.004), with more frequent primary RT (61% versus 21%, p < 0.001). Third local events were more frequent for re-BCS than mastectomy (16% versus 3%, p = 0.001), but there were no differences in breast cancer specific or overall survival. CONCLUSIONS: For isolated IBTR following BCS for DCIS and treated by mastectomy versus re-BCS (1) mastectomy was associated with less favorable initial pathology and more frequent use of primary RT, (2) re- recurrence was more frequent with re-BCS, and (3) BCSS and OS were comparable. Our data suggest a wider role for re-BCS and further study of the relationship between secondary RT and the rate of third breast events.

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Male breast cancer is a rare disease, and it is important to have a high index of suspicion in patients presenting with breast symptoms, such as a breast mass or nipple discharge. Most male patients who are diagnosed with breast cancer present with breast complaints and/or a strong family history of cancer. Here, we will present a 47-year-old male patient who was diagnosed with bilateral ductal carcinoma in situ during a routine gynecomastia surgery after massive weight loss. This case demonstrates the importance of sending breast tissue specimens for pathology, especially in a male patient.

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Introduction: Breast cancer (BC) is the most common cancer affecting women in the United States. Ductal carcinoma in situ (DCIS) is the earliest identifiable pre-invasive BC lesion. Estimates show that 14 to 50% of DCIS cases progress to invasive BC. Methods: Our objective was to identify nuclear matrix proteins (NMP) with specifically altered expression in DCIS and later stages of BC compared to non-diseased breast reduction mammoplasty and a contralateral breast explant culture using mass spectrometry and RNA sequencing to accurately identify aggressive DCIS. Results: Sixty NMPs were significantly differentially expressed between the DCIS and non-diseased breast epithelium in an isogenic contralateral pair of patient-derived extended explants. Ten of the sixty showed significant mRNA expression level differences that matched the protein expression. These 10 proteins were similarly expressed in non-diseased breast reduction cells. Three NMPs (RPL7A, RPL11, RPL31) were significantly upregulated in DCIS and all other BC stages compared to the matching contralateral breast culture and an unrelated non-diseased breast reduction culture. RNA sequencing analyses showed that these three genes were increasingly upregulated with BC progression. Finally, we identified three NMPs (AHNAK, CDC37 and DNAJB1) that were significantly downregulated in DCIS and all other BC stages compared to the isogenically matched contralateral culture and the non-diseased breast reduction culture using both proteomics and RNA sequencing techniques. Discussion: These genes should form the basis of, or contribute to, a molecular diagnostic panel that could identify DCIS lesions likely to be indolent and therefore not requiring aggressive treatment.

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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.

Asunto(s)

Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Invasividad Neoplásica , Proteínas del Tejido Nervioso , Neuropilina-1 , Neuropilina-2 , Humanos , Neuropilina-1/metabolismo , Neuropilina-1/genética , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Neuropilina-2/metabolismo , Neuropilina-2/genética , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/genética , Línea Celular Tumoral , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Transición Epitelial-Mesenquimal/genética , Animales , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratones , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/genética , Regulación Neoplásica de la Expresión Génica , Transducción de Señal

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BACKGROUND: Current guidelines do not recommend routine sentinel node biopsy (SLNB) for ductal carcinoma in situ (DCIS), except in the setting of mastectomy or microinvasive disease. This study aimed to evaluate national SLNB utilization in women undergoing upfront mastectomy for DCIS, identify predictors of SLNB utilization, and determine the percentage with a positive SLNB. METHODS: A retrospective cohort analysis was performed using the NCDB of women with clinical DCIS who underwent upfront mastectomy between 2012 and 2017. Demographic and clinicopathologic variables were compared between patients who underwent SLNB and those who did not. Multivariate logistic regression models were used to identify factors associated with SLNB utilization and positive SLNB. RESULTS: About 38,973 patients met inclusion criteria: 34,231 (88%) underwent SLNB and 4742 (12%) had no surgical axillary staging. Most patients were age 50-69 (51%), non-Hispanic White (71%), with private insurance (66%). On multivariate analysis, older patients were less likely to receive SLNB (P < .01), while patients with higher grade DCIS were more likely to undergo SLNB (P < .01). In those who underwent SLNB (n = 34,231), only 1,149 (3.4%) had nodal involvement. Non-Hispanic Black patients had increased odds of a positive SLNB (P < .01), while those with estrogen receptor positive disease were less likely to be node positive (OR 0.68, P < .001). CONCLUSIONS: While 88% of patients had a SLNB, only 3.4% were found to be node positive. Given this low rate, it is reasonable to consider SLNB omission in select patients with low grade, hormone receptor positive DCIS undergoing upfront mastectomy.

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Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Mastectomía , Biopsia del Ganglio Linfático Centinela , Humanos , Femenino , Biopsia del Ganglio Linfático Centinela/estadística & datos numéricos , Persona de Mediana Edad , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Intraductal no Infiltrante/patología , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Estudios Retrospectivos , Mastectomía/estadística & datos numéricos , Anciano , Adulto , Metástasis Linfática/patología , Axila

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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.

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PURPOSE: The current standard of treatment for ductal carcinoma in situ (DCIS) is surgery with or without adjuvant radiotherapy. With a growing debate about overdiagnosis and overtreatment of low-risk DCIS, active surveillance is being explored in several ongoing trials. We conducted a systematic review and meta-analysis to evaluate the recurrence of low-risk DCIS under various treatment approaches. METHODS: PubMed, Embase, Web of Science, and Cochrane were searched for studies reporting ipsilateral breast tumour event (IBTE), contralateral breast cancer (CBC), and breast cancer-specific survival (BCSS) rates at 5 and 10 years in low-risk DCIS. The primary outcome was invasive IBTE (iIBTE) defined as invasive progression in the ipsilateral breast. RESULTS: Thirty three eligible studies were identified, involving 47,696 women with low-risk DCIS. The pooled 5-year and 10-year iIBTE rates were 3.3% (95% confidence interval [CI]: 1.3, 8.1) and 5.9% (95% CI: 3.8, 9.0), respectively. The iIBTE rates were significantly lower in patients who underwent surgery compared to those who did not, at 5 years (3.5% vs. 9.0%, P = 0.003) and 10 years (6.4% vs. 22.7%, P = 0.008). Similarly, the 10-year BCSS rate was higher in the surgery group (96.0% vs. 99.6%, P = 0.010). In patients treated with breast-conserving surgery, additional radiotherapy significantly reduced IBTE risk, but not total-CBC risk. CONCLUSION: This review showed a lower risk of progression and better survival in women who received surgery and additional RT for low-risk DCIS. However, our findings were primarily based on observational studies, and should be confirmed with the results from the ongoing trials.

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BACKGROUND: Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer, with 5-10% of cases progressing into invasive disease. Herein, we investigated the association between HER2-low and clinico-pathological characteristics in DCIS and subsequent ipsilateral loco-regional relapse (LRR). MATERIALS AND METHODS: We accessed our prospectively maintained institutional database. HER2 status was determined by immunohistochemistry and classified as null (score 0), over-expressed (3+), and low (1+ or 2+); in situ hybridization was not considered since it is not used for routine DCIS diagnostics. RESULTS: Among 375 patients with DCIS, median age was 54 (27-88) years, with a primary tumor size < 2.5 cm in 63%, grade III in 33%, and positive hormone receptor status (HR) in 81% of cases; 71% underwent breast-conserving surgery, 34% received adjuvant endocrine and 39% radiotherapy. A total of 197 (52%) had tumors with low HER2 expression, which resulted significantly associated with grade I/II (P < .001), Ki67< 20% (P < .001), and HR-positive status (P < .001). HER2-low distribution varied from 19.61% and 50% in ER negative and ER-low (<10%) to 60% and 69% in ER high (50%-95%) and very high tumors (> 95%) (P < .001). After a median 39-month follow-up (IQR 16-65), cumulative incidences of LRR was 0.054. Among 17 patients with paired primary tumor and LRR, 5 had discordant HER2 status, with an even distribution of increased and decreased HER2 expression. CONCLUSIONS: Low HER2 expression in DCIS is associated with features of reduced aggressiveness. Importantly, changes in HER2 expression may occur prompting retesting in recurrent cases, in line with observations in invasive breast cancer.

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In breast cancer (BC) pathogenesis models, normal cells acquire somatic mutations and there is a stepwise progression from high-risk lesions and ductal carcinoma in situ to invasive cancer. The precancer biology of mammary tissue warrants better characterization to understand how different BC subtypes emerge. Primary methods for BC prevention or risk reduction include lifestyle changes, surgery, and chemoprevention. Surgical intervention for BC prevention involves risk-reducing prophylactic mastectomy, typically performed either synchronously with the treatment of a primary tumor or as a bilateral procedure in high-risk women. Chemoprevention with endocrine therapy carries adherence-limiting toxicity.

Asunto(s)

Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Carcinoma Intraductal no Infiltrante/terapia , Carcinoma Intraductal no Infiltrante/patología

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Background: This retrospective study aimed to investigate the outcomes and adverse events (AEs) associated with adjuvant radiotherapy with helical tomotherapy (hT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). Methods: Twenty-eight patients with DCIS underwent postoperative hT between 2011 and 2020. hT was chosen since it provided optimal target coverage and tolerable organ-at-risk doses to the lungs and heart when tangential 3-dimensional conformal radiotherapy (3D-CRT) was presumed to provide unfavorable dosimetry. The median total (single) dose was 50.4 Gy (1.8 Gy). The median time between BCS and the start of hT was 5 weeks (range, 4-38 weeks). Statistical analysis included local recurrence-free survival, overall survival (OS), and secondary cancer-free survival. AEs were classified according to the Common Toxicity Criteria for Adverse Events, version 5. Results: The patients' median age was 58 years. The median follow-up period was 61 months (range, 3-123 months). The 1-, 3-, and 5-year OS rates were 100% each. None of the patients developed secondary cancer, local recurrence, or invasive breast cancer during follow-up. The most common acute AEs were dermatitis (n = 27), fatigue (n = 4), hyperpigmentation (n = 3), and thrombocytopenia (n = 4). The late AE primarily included surgical scars (n = 7) and hyperpigmentation (n = 5). None of the patients experienced acute or late AEs > grade 3. The mean conformity and homogeneity indices were 0.9 (range, 0.86-0.96) and 0.056 (range, 0.05-0.06), respectively. Conclusion: hT after BCS for DCIS is a feasible and safe form of adjuvant radiotherapy for patients in whom 3D-CRT is contraindicated due to unfavorable dosimetry. During follow-up, there were no recurrences, invasive breast cancer diagnoses, or secondary cancers, while the adverse effects were mild.

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Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Mastectomía Segmentaria , Radioterapia de Intensidad Modulada , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Anciano , Radioterapia de Intensidad Modulada/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Carcinoma Intraductal no Infiltrante/radioterapia , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Intraductal no Infiltrante/patología , Adulto , Estudios Retrospectivos , Radioterapia Adyuvante/efectos adversos , Radioterapia Adyuvante/métodos , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/patología , Resultado del Tratamiento , Dosificación Radioterapéutica , Estudios de Seguimiento , Terapia Combinada

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Deep vein thrombosis (DVT) is a type of venous thromboembolism that usually involves a clot formation in the deep veins of the lower extremities. Its formation is linked to Virchow's Triad which factors in venous stasis, endothelial damage, and hypercoagulability. Venous stasis is the primary factor contributing to the development of DVT and it refers to varicosity, external pressure placed on the extremity, or immobilization due to bed rest or long flights. Clinical presentation of DVT depends on the extent and location of the thrombus with common signs including localized swelling, pain, warmth, and edema. The Wells criteria are typically applied to assess the likelihood of thrombus formation alongside D-dimer assay, ultrasound, or CT imaging. As previously mentioned, these mostly occur in the lower extremities. However, upper extremity DVT has been noted and has been linked to inherited issues with coagulation and autoimmune disorders. This report will discuss a case of left-arm DVT in a patient who underwent bilateral mastectomy with sentinel node biopsy for a diagnosis of ductal carcinoma in situ in the left breast.

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BACKGROUND: In invasive breast cancer, there are no differences among the mid- and long-term oncological safety results of nipple-sparing mastectomy (NSM), skin-sparing mastectomy (SSM), and simple mastectomy (SM). There are several reports comparing NSM and SSM with SM in the context of ductal carcinoma in situ (DCIS); however, the eligibility criteria vary among institutions, and there are no reports that compare all three surgical methods simultaneously within the same institution. This study aimed to compare the local recurrence and survival rates of the three techniques (NSM, SSM, and SM) in Japanese patients undergoing mastectomy for DCIS. METHODS: Patients undergoing NSM, SSM, or SM at our institution between 2006 and 2015 were identified, and their outcomes were analyzed. RESULTS: The mean follow-up period was 80.4 months (standard deviation [SD]: 37.1 months). NSM was performed in 152 cases, SSM in 49, and SM in 44. Five of 245 patients developed local recurrences. Four of these patients had invasive cancer. The primary endpoints of 5-year cumulative local recurrence were 2.4% (95% confidence interval [CI]: 0.0-5.0) for NSM, 2.2% (95% CI: 0.0-6.3) for SSM, and 0% (95% CI: 0.0-0.0) for SM. There were no significant differences among the 5-year local recurrence rates. CONCLUSIONS: In this single-center, retrospective study, the oncological safety of SSM and NSM for DCIS was comparable to that of conventional SM.

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Cancers evolve in a dynamic ecosystem. Thus, characterizing cancer's ecological dynamics is crucial to understanding cancer evolution and can lead to discovering novel biomarkers to predict disease progression. Ductal carcinoma in situ (DCIS) is an early-stage breast cancer characterized by abnormal epithelial cell growth confined within the milk ducts. Although there has been extensive research on genetic and epigenetic causes of breast carcinogenesis, none of these studies have successfully identified a biomarker for the progression and/or upstaging of DCIS. In this study, we show that ecological habitat analysis of hypoxia and acidosis biomarkers can significantly improve prediction of DCIS upstaging. First, we developed a novel eco-evolutionary designed approach to define habitats in the tumor intra-ductal microenvironment based on oxygen diffusion distance in our DCIS cohort of 84 patients. Then, we identify cancer cells with metabolic phenotypes attributed to their habitat conditions, such as the expression of CA9 indicating hypoxia responding phenotype, and LAMP2b indicating a hypoxia-induced acid adaptation. Traditionally these markers have shown limited predictive capabilities for DCIS upstaging, if any. However, when analyzed from an ecological perspective, their power to differentiate between indolent and upstaged DCIS increased significantly. Second, using eco-evolutionary guided computational and digital pathology techniques, we discovered distinct spatial patterns of these biomarkers and used the distribution of such patterns to predict patient upstaging. The patterns were characterized by both cellular features and spatial features. With a 5-fold validation on the biopsy cohort, we trained a random forest classifier to achieve the area under curve(AUC) of 0.74. Our results affirm the importance of using eco-evolutionary-designed approaches in biomarkers discovery studies in the era of digital pathology by demonstrating the role of eco-evolution dynamics in predicting cancer progression.

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Background: Breast cancer, as one of the most common malignancies among women globally, presents a concerning incidence rate, underscoring the importance of addressing the treatment of its precursor lesion, ductal carcinoma in situ (DCIS). Treatment decisions for DCIS, involving the balance between breast-conserving surgery (BCS) and mastectomy, remain an area requiring further investigation. This study aimed to compare influence of different surgical types on overall survival (OS) of patients with DCIS and identify specific subgroups with improved OS to develop an effective survival nomogram for patients. Methods: Patient data from the Surveillance, Epidemiology, and End Results (SEER) database for DCIS cohort from 2010 to 2020 were retrieved. Kaplan-Meier (K-M) survival curves were utilized to compare prognostic OS of patients with different surgical methods. Cox regression analysis was employed to determine prognostic factors and establish a nomogram to predict 3-, 5-, and 10-year survival rates. The model was confirmed by Concordance Index (C-index), calibration curves, and receiver operating characteristic (ROC) curves. Results: A total of 71,675 patients with DCIS were included. Patients who underwent subcutaneous mastectomy (SM) demonstrated the best OS compared to other surgical types. Additionally, adjuvant radiotherapy or chemotherapy in combination with surgery significantly improved OS compared to surgery alone. Among DCIS patients aged ≤74 years, those who underwent SM benefited the most in terms of OS, while in the age group of 63-74 years, patients who underwent BCS had significantly higher OS than those who underwent total (simple) mastectomy (TM)/modified radical mastectomy (MRM). Multiple factors were associated with improved OS in DCIS patients, and these factors were integrated into the nomogram to establish OS predictions. The C-index, calibration curves, and ROC curves indicated that the nomogram was suitable for assessing patient prognosis. Conclusions: This study demonstrated that SM treatment yielded the best survival rates for DCIS patients, providing important guidance for future surgical decision-making. Moreover, identifying multiple independent factors related to survival and establishing reliable survival nomograms can assist physicians in developing personalized treatment plans and prolonging patient survival.

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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.

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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 < 0.02). Moreover, patients with EIC had a lower likelihood for adjuvant chemotherapy recommendation. CONCLUSIONS: In early HR + HER2- IDC, an EIC correlates with a reduced genomic recurrence risk. The impact on genomic risk seems to be influenced by the extent, not merely the presence, of DCIS.

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Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Recurrencia Local de Neoplasia , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Carcinoma Intraductal no Infiltrante/genética , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Anciano , Adulto , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/análisis , Receptores de Progesterona/metabolismo , Medición de Riesgo , Estudios Retrospectivos , Genómica , Factores de Riesgo

RESUMEN

Introduction In females, carcinoma of the breast is a common malignancy. Disease management can be challenging for the treating clinician if the condition is presented in a locally advanced stage. Clinical presentation of a disease in a defined area provides a comprehensive map to target the at-risk population efficiently and select the appropriate intervention accordingly. In this retrospective study, we analyzed different factors that can affect breast carcinoma outcomes by assessing patients for a specific period of one year. Methods This is a retrospective study of carcinoma of breast patients and was conducted between 2017 and 2018. Results We reported a 25.83% incidence of breast cancer during the study period. A painful breast lump was present in 54.2% of patients, axillary nodes were present in 50% of patients, ulcers were present in 10% of patients, and nipple discharge was present in 8.5% of patients. According to the side and quadrant of involvement, the right side was the most common site of involvement in 55.7% of patients, and the upper outer quadrant was the most common quadrant involved in 61.4% of patients. The most familiar stage of the presentation was stage II, presented in 45.7% of patients. The most common histology was infiltrating ductal carcinoma, presented in 85.7% of patients. Conclusions This retrospective cohort study shows that carcinoma of the breast is a predominant malignancy among middle-aged females in developing countries such as India. This predominance is due to unawareness regarding disease symptoms and the fear of diagnosed malignancy during the investigation of symptoms. Early detection by screening and intervention at an early stage is the core of treatment success in this malignant disease. However, it is still challenging to apply screening as a tool to pick up early malignant disease in developing countries like India.