Coumarin derivatives possess diverse biological activities, encompassing antibacterial, antifungal, anticancer, antidiabetic, anti-inflammatory, and antioxidant effects. This study concentrates on the synthesis of two new coumarins: the first derived from rhizomes of Luvunga scandens and the second from 7-(diethylamino)-4-methyl-2H-chromen-2-one via bromination facilitated by NBS (N-bromosuccinimide) reagent. Their antibacterial and anticancer properties were evaluated in vitro, alongside in silico docking targeting the chromen-2-one group. Bromination of compound 1 yielded novel compound 2, while compound 4 was efficiently synthesized from 7-(diethylamino)-4-methyl-2H-chromen-2-one (3) using NBS. Testing on lung, breast, and liver cancer cell lines indicated that compound 2 effectively inhibited Staphylococcus aureus and Bacillus cereus at concentrations of 13.20 and 6.6 µM, respectively. It also demonstrated significant inhibition against MCF-7 breast cancer cells with a half-maximal inhibitory concentration (IC50) value of 50.37 ± 3.70 µM. Molecular docking revealed compound 2’s interaction with 2VF5 enzyme, elucidating its bacterial inhibition mechanism, with Gibbs energy and inhibition constant values of -7.42 kcal mol-1 and 3.62 µM, respectively. Additionally, compound 2 exhibited anticancer activity via alignment with topoisomerase 1 (3TOP): 1T8I, supported by molecular dynamics simulations illustrating strong ligand interactions. Analysis of pharmacophore kinetics highlighted the complex’s hydrophilic nature, indicating its potential therapeutic efficacy. activities antifungal antidiabetic antiinflammatory, antiinflammatory anti inflammatory, inflammatory anti-inflammatory effects coumarins 7diethylamino4methyl2Hchromen2one diethylaminomethylHchromenone 7 diethylamino methyl 2H chromen one H Nbromosuccinimide N bromosuccinimide (N-bromosuccinimide reagent vitro chromen2one chromenone group 3 (3 lung 1320 13 20 13.2 66 6 6. µM respectively MCF7 MCF MCF- halfmaximal half maximal IC50 IC (IC50 5037 50 37 50.3 370 70 3.7 2s s VF 2VF enzyme mechanism 7.42 742 42 -7.4 mol1 mol mol- 362 62 3.6 Additionally 3TOP TOP (3TOP) 1T8I TI T I interactions complexs complex nature efficacy Hchromen ( 132 13. IC5 (IC5 503 5 50. 3. 7.4 74 -7. 36 (3TOP (IC 7. -7 -

A series of novel thieno[2,3-d]pyrimidine derivatives were designed, synthesized and evaluated for their biological ability. 2-Amino-4,7-dihydro-5H-thieno[2,3-d]pyrano-3-cyanonitrile was synthesized by Gewald reaction using pyranone as substrate, malonitrile and sulfur powder as raw materials and triethylamine as base at room temperature. Subsequent amination with N,N-dimethylformamide dimethyl acetal (DMF-DMA) gave N'-(3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyran-2-yl)-N,N-dimethylmethanimidamide. In this article, the 23 thieno[2,3-d] pyrimidines were obtained by Dimroth rearrangement condensation with different anilines, 16 of them being new compounds. Meanwhile, all compounds were assessed for breast cancer MDA-MB-231 cell line bioactivity with paclitaxel (PTX) as the positive control, and all compounds in the series showed inhibitory effects on breast cancer cell MDA-MB-231. The IC50 of compound l against MDA-MB-231 is 27.6 μM, which is similar to that of PTX with an IC50 of 29.3 μM. This means that compound l exhibits comparable inhibitory activity to PTX in MDA-MB-231 cells and may be considered as a potential anti-MDA-MB-231 inhibitor. thieno2,3dpyrimidine thieno23dpyrimidine thienodpyrimidine thieno 2,3 d pyrimidine 2 3 designed ability 2Amino4,7dihydro5Hthieno2,3dpyrano3cyanonitrile 2Amino47dihydro5Hthieno23dpyrano3cyanonitrile AminodihydroHthienodpyranocyanonitrile Amino 4,7 dihydro 5H pyrano cyanonitrile 4 7 H substrate temperature N,Ndimethylformamide NNdimethylformamide N,N dimethylformamide N DMFDMA DMF DMA (DMF-DMA N3cyano4,7dihydro5Hthieno2,3cpyran2ylN,Ndimethylmethanimidamide. N3cyano47dihydro5Hthieno23cpyran2ylNNdimethylmethanimidamide NcyanodihydroHthienocpyranylNNdimethylmethanimidamide cyano c pyran yl dimethylmethanimidamide. dimethylmethanimidamide N'-(3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyran-2-yl)-N,N-dimethylmethanimidamide article thieno2,3d thieno23d thienod thieno[2,3-d anilines 1 Meanwhile MDAMB231 MDAMB MDA MB 231 MDA-MB-23 (PTX control MDAMB231. 231. IC IC5 276 27 6 27. μM 293 29 29. antiMDAMB231 antiMDAMB anti anti-MDA-MB-23 inhibitor thieno2 3dpyrimidine dpyrimidine 2, 2Amino4 7dihydro5Hthieno2 3dpyrano3cyanonitrile Hthieno dpyrano 47 4, Ndimethylformamide NN N3cyano4 3cpyran2ylN Ndimethylmethanimidamide cpyran ylN N3cyano4,7dihydro5Hthieno2,3cpyran2ylN,Ndimethylmethanimidamide ylNNdimethylmethanimidamide 3d MDAMB23 MDA-MB-2 antiMDAMB23 anti-MDA-MB-2 2Amino dihydroHthieno 7dihydro5Hthieno dpyranocyanonitrile Ncyano N3cyano cpyranylN MDAMB2 MDA-MB- antiMDAMB2 anti-MDA-MB- MDA-MB anti-MDA-MB

SUMMARY OBJECTIVE: The objective of this study was to analyze the genetic alterations of tumors within the scope of the homologous recombination deficiency gene panel in patients diagnosed with synchronous endometrial ovarian cancer who have been followed for over 5 years using next-generation sequencing. METHODS: DNA was isolated from the patient’s formalin-fixed, paraffin-embedded tissue blocks. Next-generation sequencing was performed using the Illumina capture-based sequencing method. Samples were sequenced using the Sophia HR Solution DNA Kit. RESULTS: Seven patients were included in this study. The ratios of likely pathogenic (LP)/pathogenic (P) somatic mutations in ATM (serine/threonine kinase or Ataxia-telangiectasia mutated gene), BRCA2 (breast cancer type 2 susceptibility gene), BARD1 (BRCA1 associated RING domain 1), TP53 (tumor protein p53), BIRP1 (BRCA1-interacting helicase 1 gene), PALB2 (partner and localizer of BRCA2), and CHECK2 were 21 (48.8%), 8 (18.6%), 5 (11.6%), 3 (6.9%), 2 (4.6%), 2 (4.6%), and 2 (4.6%), respectively, in endometrium, and the ratios of somatic mutations in ATM, BRCA2, TP53, BARD1, RAD54L (DNA repair/recombination protein like), BIRP1, and RAD51D (RAD51 recombinase paralog D) were 24 (60%), 6 (15%), 5 (12.5%), 2 (5%), 2 (5%), 1 (2.5%), and 1 (2.5%), respectively, in ovary. In endometrioid-synchronous endometrial ovarian cancer cases, P/LP mutations were observed in ATM and CHECK2 genes in endometrium and ATM, BRCA2, and TP53 genes in ovary. In two non-endometrioid-synchronous endometrial ovarian cancer cases, CHEK2 (checkpoint kinase 2) mutations were observed in endometrium and ATM and TP53 mutations in ovary, whereas in one case, P/LP mutations in ATM and TP53 genes were common in both tissues. CONCLUSION: Pathogenic variations confirming the diagnosis of synchronous endometrial ovarian cancer with genetic alterations were identified in all but one case. ATM gene mutation emerged as the most common alteration and has a potential association with a favorable prognosis. OBJECTIVE nextgeneration next generation METHODS patient s formalinfixed, formalinfixed formalin fixed, fixed formalin-fixed paraffinembedded paraffin embedded blocks Nextgeneration Next capturebased capture based method Kit RESULTS LP/pathogenic LPpathogenic LP /pathogenic P (P serine/threonine serinethreonine serine threonine Ataxiatelangiectasia Ataxia telangiectasia gene, , gene) BRCA breast BARD BRCA1 (BRCA 1, 1) TP TP5 tumor p53, p53 p p53) BIRP BRCA1interacting BRCAinteracting interacting PALB partner BRCA2) CHECK 48.8%, 488 48.8% 48 (48.8%) 18.6%, 186 18.6% 18 (18.6%) 11.6%, 116 11.6% 11 (11.6%) 6.9%, 69 6.9% 9 (6.9%) 4.6%, 46 4.6% 4 (4.6%) respectively RADL RAD L repairrecombination repair like, like like) RADD D RAD51 (RAD5 60%, 60 60% (60%) 15%, 15 15% (15%) 12.5%, 125 12.5% 12 (12.5%) 5%, 5% (5%) 2.5%, 25 2.5% (2.5%) ovary endometrioidsynchronous endometrioid cases PLP nonendometrioidsynchronous non CHEK checkpoint case tissues CONCLUSION prognosis p5 48.8 (48.8% 18.6 (18.6% 11.6 (11.6% 6.9 (6.9% 4.6 (4.6% RAD5 (RAD (60% (15% 12.5 (12.5% (5% 2.5 (2.5% 48. (48.8 18. (18.6 11. (11.6 6. (6.9 4. (4.6 (60 (15 12. (12.5 (5 2. (2.5 (48. (18. (11. (6. (4. (6 (1 (12. ( (2. (48 (18 (11 (4 (12 (2

Abstract Primary angiosarcomas of the breast are a rare entity with a poor prognosis. We present the case of a patient with a well-differentiated primary angiosarcoma of the breast, who initially came to our office due to self-detection of a palpable, painless, rapidly growing nodule. She had no personal or family history of breast cancer. The physical examination revealed a poorly defined nodule, with skin changes, presenting a purplish coloration of the breast. Without palpable lymphadenopathy. The mammography only revealed a nodule with irregular edges, which was given a BI-RADS category 5, so it was essential to take a core needle biopsy, obtaining a histopathological report compatible with primary angiosarcoma of the breast. A total mastectomy was performed, which is the first treatment option and the most recommended according to medical evidence limited to a few cases. In addition, a sentinel lymph node biopsy was performed, obtaining six negative results for metastasis, which should be reserved in select cases. Adjuvant chemotherapy was given, which is still controversial, given that there is no strong recommendation regarding it. Currently, the patient has a one-year disease-free period and continues to be followed up.

Resumen Los angiosarcomas primarios de la mama son una entidad rara, de mal pronóstico. Se presenta el caso de una paciente con un angiosarcoma primario de mama bien diferenciado, quien en primera instancia acudió a consulta por autodetección de nódulo palpable, indoloro, de rápido crecimiento. No contaba con antecedentes personales ni familiares para cáncer de mama. Al examen físico se evidenció un nódulo mal delimitado, con cambios cutáneos y coloración violácea de la mama. Sin adenopatías palpables. En la mamografía únicamente se evidenció un nódulo de bordes irregulares, al cual se le otorgó una categoría BI-RADS 5, por lo que fue imprescindible la toma de biopsia por aguja de corte, obteniendo un reporte histopatológico compatible con angiosarcoma primario de mama. Se optó por una mastectomía total, la cual es la piedra angular del tratamiento y lo más recomendado según la evidencia médica, limitada a pocos casos. Además, se realizó biopsia de ganglio centinela, obteniendo seis negativos para metástasis, lo cual debe reservarse en casos selectos. Se otorgó quimioterapia adyuvante, la cual aún es controversial, dado que no existe una recomendación fuerte respecto a esta. Actualmente la paciente presenta un año de periodo libre de enfermedad y continúa en seguimiento.

Abstract: Metastatic cardiac tumors are rare, and their diagnosis can be challenging, partly due to the absence of specific clinical signs and the difficulty imposed by their heterogeneous histology on characterization in non-invasive imaging studies. They are usually metastases from lung carcinoma, and breast cancer. Other malignant neoplasms, such as urothelial carcinoma, are rare entities. The case of a male patient with a history of squamous cell carcinoma of the bla dder, who underwent surgery and neoadjuvant chemotherapy is presented. Approximately 18 months later, he manifested with pulmonary embolism secondary to fragmentation of a partially thrombosed tumor mass located in the right heart chambers. The definitive biopsy following surgical excision reveals metastasis of urothelial carcinoma.

Resumen: Los tumores cardíacos metastásicos son poco frecuentes y su diagnóstico puede ser desafiante, en parte por la ausencia de signos clínicos específicos, como también por la dificultad que su histología heterogénea impone sobre su caracterización en los estudios de imágenes no invasivas. Suelen corresponder a linfomas, carcinoma de pulmón y mama. Otras neoplasias malignas, como el carcinoma urotelial, son entidades raras. Se presenta el caso de un paciente masculino con antecedente de Carcinoma Escamoso de Vejiga, sometido a cirugía y quimioterapia neoadyuvante, que aproximadamente 18 meses después debuta con cuadro de embolia pulmonar secundaria a fragmentación de masa tumoral parcialmente trombosada alojada en cavidades cardiacas derechas. La biopsia definitiva posterior a exéresis quirúrgica demuestra metástasis de carcinoma urotelial.

Resumen Las metástasis en la glándula tiroides a partir de tu mores malignos no tiroideos son raras pero significativas. A menudo son asintomáticas, lo que indica tumores primarios en etapas avanzadas y un mal pronóstico. Aunque infrecuentemente, el cáncer de mama puede metastatizar en la glándula tiroides. Presentamos el caso de una mujer de 56 años con antecedente de cáncer de mama que consultó por bocio nodular. El examen físico y las imágenes revelaron un nódulo tiroideo y ganglios linfáticos cervicales con características sospechosas. La punción aspiración con aguja fina confirmó la presencia de células epiteliales atípicas en el nódulo tiroideo y los ganglios linfáticos. Una evaluación adicional, que incluyó tomografía por emisión de positrones, biopsia histológica e inmunohistoquímica, respaldó el diagnóstico de cáncer de mama metastásico en la glándula tiroides. Debido a la extensión local de la enfermedad, no fue factible realizar una tiroidectomía total. Se inició el tratamiento con ri bociclib y letrozol, pero desafortunadamente la paciente tuvo una progresión desfavorable con el desarrollo de metástasis en el sistema nervioso. El carcinoma metas tásico en la glándula tiroides es raro, pero ha aumentado debido a las técnicas de diagnóstico mejoradas. El cáncer de mama puede metastatizar en la tiroides. El diagnóstico implica imágenes, punción aspiración con aguja fina e in munohistoquímica. Las opciones de tratamiento incluyen cirugía, radioterapia y quimioterapia, pero el pronóstico generalmente es desfavorable.

Abstract Metastases to the thyroid gland from nonthyroidal malignant tumors are rare but significant. They are often asymptomatic, indicating advanced-stage primary tumors and poor prognosis. Although infrequently, breast cancer (BC) can metastasize to the thyroid gland. We present the case of a 56-year-old woman with a history of BC who pre sented with a nodular goiter. Physical examination and im aging revealed a thyroid nodule and cervical lymph nodes with suspicious features. Fine-needle aspiration biopsy (FNAB) confirmed the presence of atypical epithelial cells in the thyroid nodule and lymph nodes. Further evaluation, including positron emission tomography, histological biop sy, and immunohistochemistry, supported the diagnosis of metastatic BC to the thyroid gland. Due to the local extent of the disease, total thyroidectomy was not feasible. The treatment with ribociclib and letrozole was initiated, but unfortunately, the patient had an unfavorable progression with the development of metastasis in the nervous system. Metastatic carcinoma to the thyroid gland is rare but has increased due to improved diagnostic techniques. BC can metastasize to the thyroid. Diagnosis involves imaging, FNAB, and immunohistochemistry. Treatment options include surgery, radiotherapy, and chemotherapy, but the prognosis is generally poor.

Resumen Introducción : La región selar es un sitio infrecuente de metástasis, encontrándose en el 1% de las cirugías hipofisarias. Los tumores primarios más habituales son mama y pulmón. En general son diagnosticadas en pa cientes con enfermedad avanzada, aunque pueden ser el debut de la enfermedad oncológica. Métodos : Análisis retrospectivo de las características clínicas, bioquímicas, radiológicas de pacientes con me tástasis selares o hipofisarias (MS) durante el periodo 2009-2020. Resultados : Se reportaron 18 casos de pacientes, 11 de ellos con confirmación histológica. La mediana de edad fue 53 años (rango: 35-75), 53% hombres. La loca lización del tumor primario fue: 8 pulmón, 6 mama, 1 carcinoma folicular de tiroides, 1 linfoma Hodgkin y 2 carcinomas renales de células claras. La media de tiem po entre el diagnóstico del tumor primario y la aparición de la MS -en los casos de presentación metacrónica- fue 108 meses (rango: 11-180). En 8 pacientes (44.4%), el diagnóstico de la neoplasia primaria se hizo a partir del hallazgo de la masa selar. Diabetes insípida, hipopitui tarismo, trastornos visuales, oftalmoplejía y cefalea se presentaron en el 78, 77, 61, 39 y 39%, respectivamente. Quince pacientes presentaron masas con extensión su pra/paraselar; y 3 lesión limitada a la hipófisis y tallo. Fueron operados 11/18 por vía transesfenoidal, para diagnóstico y/o descompresión. Fallecieron 17, con una mediana de sobrevida de 6 meses (1- 36). Discusión : La sospecha de MS debe estar presente ante una masa selar y supraselar con captación difusa del gadolinio, diabetes insípida, hipopituitarismo y/o disfunción visual, aun en pacientes sin antecedentes oncológicos.

Abstract Introduction : Sellar metastases (SM) are rare mani festations of malignancy. Breast and lung cancer are the most common primary tumors. Most cases are di agnosed in patients with advanced malignant disease; however, symptoms of pituitary involvement can pre cede the diagnosis of the primary tumor. Methods : Retrospective analysis of symptoms at presentation, hormonal, radiological and histological findings, management, and outcome of patients with SM from 2009 to 2020. Results : Eighteen patients´cases were included, 11 with histological confirmation. Median (m) age was 53 years (range 35-75), 53% male. Primary malignant tu mors: 8 lungs, 6 breast, 1 follicular thyroid carcinoma, 1 Hodgkin lymphoma, and 2 clear cell renal carcinomas. The m time between the diagnosis of the primary neo plasm and the occurrence of the SM was 108 months (range: 11-180). In 8 patients the diagnosis of the primary neoplasm was made after the finding of the symptom atic sellar mass. Insipidus diabetes, adenohypophysis deficit, visual disorders, headache, and cranial nerve deficits were evident in 78, 77, 61, 39 and 39% of the cases, respectively. Fifteen patients harbored supra / parasellar masses, in three a lesion was limited to the pituitary gland, and stalk. Eleven out of 18 (61.1%) of the patients were operated on by the trans-sphenoidal approach, for diagnostic and / or decompressive pur poses. Eighteen died, with a median survival time of 6 months (1-36). Discussion : In the presence of a pituitary lesion with diffuse gadolinium uptake, associated with insipidus diabetes and / or visual disorder SM should be suspected even in patients without a history of oncological disease.

Resumen La neumatosis intestinal y el neumoperitoneo no son entidades patológicas en sí mismas, son signos radio lógicos que resultan de alguna condición subyacente. En general, estos se asocian con procesos graves intra-abdominales que resultan en cirugías de urgencias con resecciones de intestino. A continuación, presentamos el caso de una mujer de 80 años, con diagnóstico de cáncer de mama estadio IV en tratamiento con ful vestrant y ribociclib, que ingresó a nuestro centro por dolor abdominal y vómitos. Se diagnosticó neumatosis intestinal y neumoperitoneo por lo que se procedió a laparotomía exploradora por sospecha de isquemia intestinal. No hubo evidencia de necrosis o perforación intestinal por lo que no se realizó resección. Evolucionó durante la internación de forma satisfactoria y en el control tomográfico al mes del egreso hubo resolución completa del cuadro. Si bien está descrito esta afectación en relación a los episodios de aumento de presión intraabdominal, como en la emesis, también se describió en pacientes con neoplasias, principalmente del tubo digestivo, ya sea por daño local o por toxicidad asociada a la quimioterapia. No encontramos reportes en la literatura de neumatosis intestinal vinculada a esta medicación antineoplásica en humanos. Probablemente en nuestro caso la etiolo gía haya sido multifactorial. Es posible que el ribociclib haya jugado un rol, ya sea por un mecanismo indirecto asociado a los vómitos y la inmunosupresión o directo sobre el enterocito debido a su mecanismo de acción celular no específico.

Abstract Pneumatosis intestinalis and pneumoperitoneum are not pathological entities in themselves, they are radiological signs that result from some underlying condition. In general, these are associated with serious intra-abdominal processes that result in emergency surgeries with bowel resections. Below, we present the case of an 80-year-old woman, diagnosed with stage IV breast cancer under treatment with fulvestrant and ribociclib, who was admitted to our center due to abdominal pain and vomiting. She was diagnosed with intestinal pneumatosis and pneumoperitoneum, so she underwent exploratory laparotomy for sus pected intestinal ischemia. There was no evidence of intestinal necrosis or perforation, so resection was not performed. She progressed satisfactorily during hospitalization and in the tomographic control one month after discharge there was complete resolution of the condition. Although this condition has been described in relation to episodes of increased intra-abdominal pressure, such as emesis, it has also been described in patients with neoplasms, mainly of the digestive tract, either due to lo cal damage or toxicity associated with chemotherapy. We found no reports in the literature of pneumatosis intesti nalis linked to this antineoplastic medication in humans. Probably in our case the etiology was multifactorial. It is possible that ribociclib played a role, either through an indirect mechanism associated with vomiting and im munosuppression or directly on the enterocyte due to its non-specific cellular mechanism of action.

Resumen Introducción: El cáncer de mama es una enfermedad de importancia mundial, caracterizada por un crecimiento anormal de las células que están en el tejido mamario, causada por distintos factores, los cuales pueden ser genéticos, esporádicos, hereditarios y ambientales. Objetivo: Analizar cómo se relacionan los diferentes factores con vigencia y no vigencia de la mamografía en mujeres chilenas dentro del rango etario entre 50 a 69 años, en el año 2023. Método: Estudio observacional, analítico y descriptivo. De esta forma, se analizaron dos grupos que investigar: las mujeres de 50 a 69 años con mamografía vigente (control) y las mujeres que no la tenían vigente (caso), para poder relacionar diversas variables en relación con ello. El total de la muestra fue de 207 mujeres, 119 controles y 88 casos. Resultados: Según la encuesta, las mujeres mayores de 59 años con una odds ratio de 1 (p < 0,87) no tenían diferencias respecto a la vigencia de su mamografía con las menores de 60 años, no así en las mujeres que no se preocupan por su salud, las cuales tienen cuatro veces más probabilidad de no tener la mamografía vigente (p < 0,81). Por otra parte, las mujeres que no poseían el conocimiento sobre la función de la mamografía poseen siete veces más probabilidad de no tener su mamografía vigente. Conclusiones: Es necesario realizar un abordaje diferenciado en cada uno de los factores, tanto de riesgo como protector, asociado al desarrollo del cáncer de mama.

Abstract Introduction: Breast cancer is a disease of global importance, characterized by abnormal growth of cells in the breast tissue, caused by different factors, which can be genetic, sporadic, hereditary and environmental. Objective: Analyze how the different factors are related to validity and non-validity of mammography in Chilean women within the age range between 50 and 69 years, in the year 2023. Method: Observational, analytical and descriptive study. In this way, the two groups to be investigated were analyzed: women between 50 and 69 years old with a current mammogram (control) and women who did not have it current (case), in order to relate various variables in relation to it. The total sample was 207 women, 119 controls and 88 cases. Results: According to the survey, women over 59 years of age with an odds ratio 1 (p < 0.87) had no differences regarding the validity of their mammography with those under 60 years of age, but not in women who do not worry about their health, which are four times more likely to not have a current mammogram (p < 0.81). On the other hand, women who did not have knowledge about the function of mammography are seven times more likely to not have a current mammogram. Conclusions: It is necessary to carry out a differentiated approach to each of the factors, both risk and protective, associated with the development of breast cancer.

Abstract This case report presents a rare manifestation of a pigmented cutaneous metastasis of breast carcinoma with a zosteriform distribution. A 77-year-old woman, previously diagnosed with invasive ductal carcinoma of the breast, exhibited pigmented lesions resembling shingles on the left thoracodorsal region. Dermoscopic and histopathological examinations confirmed invasive carcinoma of mammary origin associated with melanocytic colonization. The zosteriform pattern, though rare, has been reported in cases of cutaneous metastasis from breast cancer. Treatment options include addressing the primary tumor and direct approaches such as surgery or radiotherapy for skin lesions. This report highlights the importance of clinical suspicion, histopathological evaluation, and immunohistochemical examinations for accurate diagnosis, enabling timely and appropriate treatment for improved patient outcomes.

Resumo Este relato de caso apresenta uma manifestação rara de metástase cutânea pigmentada de câncer de mama com distribuição zosteriforme. Uma mulher de 77 anos, previamente diagnosticada com carcinoma ductal invasivo de mama, apresentava lesões pigmentadas semelhantes a herpes-zóster na região toracodorsal esquerda. Os exames dermatoscópico e histopatológico confirmaram carcinoma invasivo de origem mamária associado à colonização melanocítica. O padrão zosteriforme, embora raro, já foi relatado em casos de metástases cutâneas de câncer de mama. As opções de tratamento incluem abordar o tumor primário e abordagens diretas, como cirurgia ou radioterapia para lesões cutâneas. Este relatório destaca a importância da suspeita clínica, avaliação histopatológica e exames imuno-histoquímicos para um diagnóstico preciso, permitindo um tratamento oportuno e apropriado para melhores resultados dos pacientes.

ABSTRACT Introduction: Every year more than 2.3 million cases of breast cancer are registered, making it the most common type of cancer among adults. The association between breast cancer and occupational factors is an issue that has been studied in the literature since the beginning of the 18th century. Technological developments have allowed a more in-depth study of the relationship between breast cancer and occupational factors such as exposure to chemicals, pesticides, metals and also sources of exposure to ionising and non-ionising radiation.The aim of the present literature review is to complete an update on the scientific knowledge about the relationship between occupational exposure to ionising radiation in healthcare workers and the development of breast cancer. Methodology: A research was carried using Medline with the PubMed search engine and Elsevier with the Science Direct search engine. The search words used were a combination of breast cancer, occupational exposure, ionizing radiation and healthcare workers. A research was also carried out in Revista Portuguesa de Saúde Ocupacional, using the terms “Breast Cancer” and “Ionizing Radiation”. Discussion/Conclusions: Current literature is not unanimous about the specific clinical and pathological features of breast cancer possibly linked to occupational settings. Healthcare professionals such as radiology technicians, nurses, orthopaedic surgeons and interventional cardiologists are especially vulnerable to this type of exposure, particularly to ionising radiation. However, some studies have pointed to a difficulty in establishing a causal relationship between these factors due to the number of variables involved, such as the duration and intensity of exposure and the influence of other risk factors. Changes in equipment, procedures and protective measures have resulted in lower doses in recent years, which means that the risk of breast cancer is low at current levels of occupational exposure to ionizing radiation.

RESUMO Introdução: Todos os anos são registados mais de 2,3 milhões de casos de cancro da mama, o que o torna o tipo cancro mais comum entre os adultos. A associação entre o cancro da mama e fatores ocupacionais é uma questão que tem vindo a ser estudada na literatura desde o início do século XVIII. Os desenvolvimentos tecnológicos permitiram um estudo mais aprofundado sobre a relação entre o cancro da mama e os fatores profissionais como a exposição a produtos químicos, pesticidas, metais e também fontes de exposição a radiação ionizante e não ionizante. O objetivo da presente revisão de literatura é incidir na relação entre a exposição ocupacional a radiação ionizante em trabalhadores da saúde e o desenvolvimento de cancro da mama. Metodologia: Foi efetuada uma pesquisa na Medline, com o motor de busca PubMed e na Elsevier, com o motor de busca Science Direct. As palavras de pesquisa usadas foram uma combinação dos termos breast cancer, occupational exposure, ionizing radiation e healthcare workers. Foi também realizada pesquisa na Revista Portuguesa de Saúde Ocupacional utilizando os termos “Cancro de mama” e “Radiação Ionizante”. Discussão/Conclusão: A literatura atual não é unânime quanto às características clínicas e patológicas específicas do cancro da mama possivelmente ligadas a contextos profissionais. Os profissionais de saúde, tais como técnicos de radiologia, enfermeiros, cirurgiões ortopédicos e cardiologistas de intervenção são especialmente vulneráveis a este tipo de exposição, nomeadamente à radiação ionizante. No entanto, alguns estudos apontaram para uma dificuldade em estabelecer uma relação causal entre estes fatores e o desenvolvimento de doença devido ao número de variáveis envolvidas, tais como a duração e intensidade da exposição e à influência de outros fatores de risco. As mudanças no equipamento, procedimentos e medidas de proteção resultaram em doses mais baixas nos anos mais recentes, o que significa que o risco de cancro da mama é baixo nos níveis atuais de exposição profissional à radiação ionizante.

Abstract This article aims to map the global scientific production on social or cultural representations and breast cancer in Public Health and discuss how it is presented in the literature. We conducted a scoping review guided by the question: “How are cultural or social representations in the context of breast cancer described in the global scientific Public Health production?”. We searched for works in five scientific literature sources and included 45 studies. The analytical process followed the content analysis technique in the thematic modality. The analyzed collection can be thematized into the following categories: (1) Compromised body image and interactions, (2) Spirituality, (3) Loss of control over life, (4) Going on with life, and (5) Association with ethnic-racial issues. Despite advances in biomedicine, we observed that representations of breast cancer still have metaphors associated with cancer in the last century. We conclude that, among other aspects, care for women with breast cancer cannot be guided only by biomedical and epidemiological approaches since this disease is traversed by knowledge that competes with these approaches. question How production. . production?” 4 studies modality categories 1 (1 interactions 2 (2 Spirituality 3 (3 life (4 5 (5 ethnicracial ethnic racial issues biomedicine century aspects production? (

Resumo O objetivo deste artigo é mapear a produção científica global sobre representações sociais ou culturais e câncer de mama no campo da saúde coletiva e discutir como esse fenômeno se apresenta na literatura. Foi realizada uma revisão de escopo, tendo como norte a seguinte pergunta: “Como representações culturais ou sociais no contexto do câncer de mama são descritas na produção científica global no âmbito da saúde coletiva?”. As buscas foram realizadas em cinco fontes de literatura científica, sendo incluídos 45 estudos. O tratamento analítico seguiu a técnica de análise de conteúdo na modalidade temática. O acervo analisado pode ser tematizado nas seguintes categorias: (1) Comprometimento na imagem corporal e nas interações; (2) Espiritualidade; (3) Perda do controle da vida; (4) Seguir com a vida e (5) Associação a questões étnico-raciais. Apesar dos avanços da biomedicina, observa-se que nas representações do câncer de mama ainda permanecem metáforas associadas ao câncer no século passado. Conclui-se que, dentre outros aspectos, a atenção a mulheres com câncer de mama não pode ser pautada apenas pelas abordagens biomédica e epidemiológica, uma vez que essa doença é atravessada por saberes que competem com essas abordagens. escopo pergunta Como coletiva. . coletiva?” 4 estudos temática categorias 1 (1 interações 2 (2 Espiritualidade 3 (3 (4 5 (5 étnicoraciais. étnicoraciais étnico raciais. raciais étnico-raciais biomedicina observase observa passado Concluise Conclui aspectos epidemiológica coletiva? (

Abstract Introduction : Triple negative breast cancer endophe notype (TNBC) is one of the least frequent and without therapeutic target; therefore we propose to study the correlation of PD-L1 immune checkpoint with the es tablishment of tumor microenvironment assessed by intratumoral stromal lymphocyte infiltration (TILS) and its importance in clinical practice. Methods : A retrospective case-control study was performed, with 31 cases of triple-negative infiltrat ing breast carcinoma and 57 unmatched controls of Luminal A, Luminal B and HER-2 endophenotype seen in one year. The following variables were evaluated: histologic type and grade, PD-L1 expression with clone 22C3, TILS, lymphovascular invasion, tumor size, lymph node involvement and metastasis. Statistical analysis was performed with the chi-square test and Spearman correlation coefficient test. Results : a statistically significant negative correlation was found between TILS and PD-L1 (rho - 0.106, p 0.025), indicating that the higher the expression of PD-L1, the lower the intratumoral lymphocytic infiltration. In the TILS B (10-40% TILS) and C (40-90% TILS) groups where there was a marked intratumoral inflammatory infiltrate, a greater number of patients were negative for PD-L1 (CPS <10) with 16 and 10 cases, respectively. For TNBC cases a negative association coefficient was identified (rho -0.378) with statistical significance (p 0.01). Discussion : The association between TNBC, TILS and PDL1 expression was established, which is important for the establishment of target therapies and the develop ment of precision medicine.

Resumen Introducción : El endofenotipo de cáncer de mama triple negativo (TNBC) es uno de los menos frecuentes y sin diana terapéutica, por tanto, se plantea estudiar la correlación del punto de control inmunológico PD-L1 con el establecimiento de microambiente tumoral evaluado por la infiltración linfocitaria intratumoral estromal (TILs) y su importancia en la práctica clínica. Métodos : Se realizó un estudio retrospectivo de casos y controles, con 31 casos de carcinoma infiltrante de la mama triple negativo y 57 controles no pareados de endofenotipo Luminal A, Luminal B y HER-2 atendidos en un año. Se evaluaron las variables: tipo y grado his tológico, expresión PD-L1 con el clon 22C3, TILs, invasión linfovascular, tamaño tumoral, compromiso de ganglios linfáticos y metástasis. El análisis estadístico se ejecutó con la prueba de chi cuadrado y prueba de coeficiente de correlación de Spearman. Resultados : Se encontró una correlación negativa estadísticamente significativa entre TILs y PD-L1 (rho - 0.106, p 0.025), indicando que a mayor expresión de PD-L1, es menor la infiltración linfocitaria intratumo ral. En los grupos de TILs B (10-40% TILs) y C (40-90% TILs) donde se presenta marcado infiltrado inflamatorio intratumoral se evidenció mayor número de pacientes negativos para PD-L1 (CPS <10) con 16 y 10 casos res pectivamente. Para los casos TNBC se logró identificar un coeficiente de asociación negativa (rho -0.378) y con significancia estadística (p 0.01). Discusión : Se estableció la asociación de TNBC, TILs y expresión de PDL1, lo cual es importante para la instau ración de terapias diana y el desarrollo de la medicina de precisión.

Resumo O objetivo deste artigo é mapear a produção científica global sobre representações sociais ou culturais e câncer de mama no campo da saúde coletiva e discutir como esse fenômeno se apresenta na literatura. Foi realizada uma revisão de escopo, tendo como norte a seguinte pergunta: “Como representações culturais ou sociais no contexto do câncer de mama são descritas na produção científica global no âmbito da saúde coletiva?”. As buscas foram realizadas em cinco fontes de literatura científica, sendo incluídos 45 estudos. O tratamento analítico seguiu a técnica de análise de conteúdo na modalidade temática. O acervo analisado pode ser tematizado nas seguintes categorias: (1) Comprometimento na imagem corporal e nas interações; (2) Espiritualidade; (3) Perda do controle da vida; (4) Seguir com a vida e (5) Associação a questões étnico-raciais. Apesar dos avanços da biomedicina, observa-se que nas representações do câncer de mama ainda permanecem metáforas associadas ao câncer no século passado. Conclui-se que, dentre outros aspectos, a atenção a mulheres com câncer de mama não pode ser pautada apenas pelas abordagens biomédica e epidemiológica, uma vez que essa doença é atravessada por saberes que competem com essas abordagens.

Abstract This article aims to map the global scientific production on social or cultural representations and breast cancer in Public Health and discuss how it is presented in the literature. We conducted a scoping review guided by the question: “How are cultural or social representations in the context of breast cancer described in the global scientific Public Health production?”. We searched for works in five scientific literature sources and included 45 studies. The analytical process followed the content analysis technique in the thematic modality. The analyzed collection can be thematized into the following categories: (1) Compromised body image and interactions, (2) Spirituality, (3) Loss of control over life, (4) Going on with life, and (5) Association with ethnic-racial issues. Despite advances in biomedicine, we observed that representations of breast cancer still have metaphors associated with cancer in the last century. We conclude that, among other aspects, care for women with breast cancer cannot be guided only by biomedical and epidemiological approaches since this disease is traversed by knowledge that competes with these approaches.