CRISPR/Cas9-mediated activation of CDH1 suppresses metastasis of breast cancer in rats

BACKGROUND Cancer is a life-threatening disease that affects approximately 18 million individuals worldwide. Breast cancer is the most common female neoplasm globally with more than 276,480 new cases of invasive breast cancer expected to be diagnosed in women in the U.S. alone in 2020. Genetic and epigenetic factors play role in the carcinogenesis and progression of this disease. In this study, MCF-7 adenocarcinoma cells were transfected with CRISPR/Cas9 plasmid to either knock out CDK11 or to activate CDH1. Treated cells were allografted into the mammary glands of female rats (150­190 g, 6­8 weeks) to evaluate the capability of these cells to control cancer progression and metastasis. RESULTS qPCR data revealed a significant downregulation of CDK11 and upregulation of CDH1. Cell cycle analysis and apoptosis assays indicated the knockout of CDK11 and simultaneous activation of CDH1 resulted in cell cycle arrest at G2/M phase and accumulation of cells at G2. Meanwhile, the percentage of cells that underwent late apoptosis increased in both genome editing hits. Histopathological sectioning data indicated that untransfected MCF-7 cells were capable of developing tumors in the mammary gland and initiation g angiogenesis. Transfected cells significantly restricted cancer cell infiltration/invasion by minimally localizing tumors and inhibiting angiogenesis. CONCLUSIONS Although further investigation is needed, the present data indicate the potentiality of using CRISPR/Cas9-based therapy as a promising approach to treat breast cancer. Impact: these data indicate targeting cancer-related genes via any genome editing tool might represent a novel approach to combat cancer.

ICON 2013: Practical consensus recommendations for hormone receptor-positive Her2-negative advanced or metastatic breast cancer.

The management of hormone receptor‑positive Her2‑negative breast cancer patients with advanced or metastatic disease is a common problem in India and other countries in this region. This expert group used data from published literature, practical experience, and opinion of a large group of academic oncologists, to arrive at practical consensus recommendations for use by the community oncologists.

Breast Metastases from Extramammary Malignancies: Typical and Atypical Ultrasound Features

Breast metastases from extramammary malignancies are uncommon. The most common sources are lymphomas/leukemias and melanomas. Some of the less common sources include carcinomas of the lung, ovary, and stomach, and infrequently, carcinoid tumors, hypernephromas, carcinomas of the liver, tonsil, pleura, pancreas, cervix, perineum, endometrium and bladder. Breast metastases from extramammary malignancies have both hematogenous and lymphatic routes. According to their routes, there are common radiological features of metastatic diseases of the breast, but the features are not specific for metastases. Typical ultrasound (US) features of hematogenous metastases include single or multiple, round to oval shaped, well-circumscribed hypoechoic masses without spiculations, calcifications, or architectural distortion; these masses are commonly located superficially in subcutaneous tissue or immediately adjacent to the breast parenchyma that is relatively rich in blood supply. Typical US features of lymphatic breast metastases include diffusely and heterogeneously increased echogenicities in subcutaneous fat and glandular tissue and a thick trabecular pattern with secondary skin thickening, lymphedema, and lymph node enlargement. However, lesions show variable US features in some cases, and differentiation of these lesions from primary breast cancer or from benign lesions is difficult. In this review, we demonstrate various US appearances of breast metastases from extramammary malignancies as typical and atypical features, based on the results of US and other imaging studies performed at our institution. Awareness of the typical and atypical imaging features of these lesions may be helpful to diagnose metastatic lesions of the breast.

Melanoma metastatic to a ruptured silicone breast implant capsule.

Metastasis to the breast is rare and most commonly represents spread from a contra-lateral primary mammary carcinoma. Metastasis of solid non-mammary carcinoma is very rare and melanoma and neuro-endocrine bronchogenic carcinoma are the more common primary neoplasms implicated. In up to half of affected individuals, there may be no prior diagnosis of malignancy. Breast metastasis by melanoma to our knowledge has never been described to an augmented breast, moreover, to a ruptured implant capsule.

Sodium iodide symporter, estrogen receptor, and progesterone receptor expression in carcinoma breast - An immunohistochemical analysis.

Background: Sodium iodide symporter (NIS), a transporter of iodine is essential for thyroid hormone biosynthesis. It also plays a role in the radioiodine treatment of thyroid cancers. NIS mediated radioiodine transport to breast cancers is under active investigation due to its potential therapeutic utility. Cellular localization and quantification using immunohistochemistry may provide clues for its utility in management of carcinoma breast. Materials and Methods: Human NIS (hNIS) expression was therefore assessed by utilizing a rabbit polyclonal antibody raised against a cloned hNIS in different grades of infiltrating duct carcinoma of breast and its metastatic deposits namely in lymph nodes, bone marrow, and endometrium. Further, hNIS expression was compared with prognostic markers namely estrogen receptor (ER) and progesterone receptor (PR). Results: hNIS was positive in 90.6% cases (29/32) and Scarff-Bloom-Richardson grading was done in 25 cases and 23 cases were NIS positive. Among nongraded cases, 2/2 cases of carcinoma in-situ were positive and 4/5 were positive in cases having post therapy residual tumor status. The strong positivity for hNIS was seen irrespective of ER or PR status and of grade of breast carcinoma and correlated well with western blot analysis. In all the three metastatic sites, NIS was positive in the tumor. Conclusion: These findings indicate the utility of immnohistochemistry for NIS as a new potential prognostic marker and may provide guidance for possible radio iodine therapy in breast cancer patients.

Breast and axillary lymph nodes metastasis five years after radical nephrectomy for renal cell carcinoma a case report and review of the literature

Breast is an uncommon and rare site for metastasis. Primary and secondary tumors of the breast need to be differentiated as management is different. We present a 67 year old female patient with two breast lumps and an axillary lymph node, 5 years after nephrectomy for Renal Cell Carcinoma [RCC]. Mammogram report showed a dense spiculated mass at right upper outer quadrant and a retroareolar mass associated with clustered micro calcifications. Fine Needle Cytology and trucut biopsy were inconclusive. Computer Topography [CT] abdomen did not show evidence of RCC recurrence. After discussion with the patient, she underwent mastectomy with axillary clearance and the final histopathology report was consistent with metastasis from RCC. The management of this case is discussed

Breast metastatic alveolar rhabdomyosarcoma: FNA findings

A 25-year-old woman, a known case of vulvar rhabdomyosarcoma presented with bilateral breast nodules. Fine needle aspiration was performed. The smears revealed numerous round malignant cells, positive for malignancy. Histopathologic and immunocytochemical examination confirmed the diagnosis of metastatic alveolar rhabdomyosarcoma. The cytological findings of alveolar rhabdomyosarcoma of the breast are rarely reported. The clinical history and immunocytochemical study contributed to the diagnosis of metastatic alveolar rhabdomyosarcoma

[Investigation of gelatinase- B enzyme role in invasion and metastasis of breast cancer]

Gelatinase B or collagenase type IV is a 92 kDa protein. In case of over-expression of the gene, because of its collagenase activity, it can be involved in metastasis activity of few cancers e.g. bladder, colorectal and gastric carcinoma. Single nucleotide substitution base polymorphism of C to T at -1562 of promotor region can increase gene expression by decreasing transcription inhibitor proteins binding at T alleles. The aim of this case-control study is to investigate the role of this polymorphism in development and invasion of breast cancer in Isfahan women population. At this study 90 breast cancer patients with metastasis and 100 healthy controls were analyzed using polymerase chain reaction-restriction fragment length polymorphism assay [PCR-RFLP]. The mean of follow up period was 2 years. Patients were checked every 3-5 months Data analysis showed a close association between the presence of T allele and invasion of breast cancer [OR = 5.85, 95% CI: 2.64-12.93, p <0.0001]. According to our findings, the major role of this polymorphism is in cancer cell metastasis and invasion of these cells to adjacent tissues

Spinal and bilateral breast metastases of embryonal rhabdomyosarcoma.

A case of spinal and bilateral breast metastasis was reported The primary tumor was an embryonal rhabdomyosarcoma of the left hand. Intralesional resection of metastatic spinal sarcoma was done with concurrence chemotherapy and radiotherapy. The literatures of these rare conditions were reviewed.

Metastatic breast cancer: do current treatments improve quality of life? A prospective study / Câncer de mama metastático: a abordagem atual melhora a qualidade de vida? Um estudo prospectivo

CONTEXT AND OBJECTIVE: In metastatic breast cancer cases, the currently available therapeutic approaches provide minimal improvement in survival. As such, quality of life (QOL) becomes one of the main objectives of treatment. It is not known whether current treatments derived from trials improve QOL. The aim was to evaluate changes in QOL among metastatic breast cancer patients receiving treatment derived from trials. DESIGN AND SETTING: Prospective observational QOL survey in a tertiary cancer center. METHODS: To evaluate the influence of current treatments on patients' QOL, the Medical Outcomes Study Short Form-36 (SF-36) and the Beck Depression Inventory (BDI) were applied on three occasions: before starting treatment and at the 6th and 12th weeks, to consecutive metastatic breast cancer patients over a one-year period. RESULTS: We found an improvement in QOL in the sample evaluated (n = 40), expressed by changes in the overall SF-36 score (p = 0.002) and the BDI (p = 0.004). Taken individually, the SF-36 components Pain, Social Functioning and Mental Health also improved significantly. Patients with worse initial performance status and secondary symptoms displayed greater improvement than those with better initial performance status and asymptomatic disease (p < 0.001). Patients who received more than one type of therapy showed larger gains than those given only one type (p = 0.038). CONCLUSIONS: In our environment, current metastatic breast cancer treatments can improve QOL, especially among symptomatic patients and those with low performance status.

CONTEXTO E OBJETIVO: As abordagens terapêuticas atuais para o câncer de mama metastático não asseguram aumento na sobrevida. Sendo assim, qualidade de vida passa a ser um dos principais objetivos do tratamento. Apesar disso, desconhecemos a influência dos tratamentos atualmente utilizados na qualidade de vida dessa população. O objetivo do estudo foi avaliar a influência do tratamento oncológico na qualidade de vida de portadoras de câncer de mama metastático. TIPO DE ESTUDO E LOCAL: Estudo prospectivo da variação da qualidade de vida de portadoras de câncer de mama metastático tratadas em um centro médico terciário. MÉTODOS: Realizamos um levantamento prospectivo da influência dos tratamentos oncológicos, incluindo quimioterapia, tratamento hormonal, radioterapia, cirurgia e suporte clínico, na qualidade de vida de pacientes tratadas no Centro de Tratamento e Pesquisa Hospital do Câncer, em São Paulo. Utilizamos para isso o Medical Outcomes Study's Short Form-36 (SF-36) e o Inventário de Depressão de Beck (IDB), aplicados em três ocasiões: antes do início, na 6ª e na 12ª semanas após o início do tratamento. RESULTADOS: Encontramos melhora de qualidade de vida na amostra avaliada (n = 40), expressa pela variação dos índices do SF-36 (p = 0,002) e do IDB (p = 0,004). Os componentes do SF-36 que apresentaram ganhos mais significativos foram dor, aspecto social e saúde mental. Como esperado, as pacientes com piores Performance Status (PS) e com sintomas secundários presentes apresentaram maiores ganhos em sua qualidade de vida que as de bom PS e as assintomáticas (p < 0,001). Da mesma forma, aquelas que receberam mais de uma modalidade terapêutica em comparação com as que só receberam um tipo de tratamento (p = 0,038). CONCLUSÕES: Em nosso meio, a abordagem atual para o câncer de mama metastático mostrou-se capaz de melhorar a qualidade de vida das pacientes, especialmente das que se apresentam com sintomas secundários à doença de base ou com baixo PS.

Frequency and characteristics of breast lymphomas presenting to a tertiary care hospital Pakistan

To assess the relative frequency of [primary and secondary] mammary lymphomas presenting to a tertiary care hospital, Pakistan and its categorization according to WHO classification of lymphoid neoplasms. All NHLs [nodal and extra nodal] diagnosed in the section of histopathology during 1992-2004 were retrieved and reviewed. All patients [n=30] diagnosed with lymphomatous involvement of the breast were selected. Distinction between primary and secondary breast lymphomas was not made owing to lack of availability of clinical information. A total of 5637 breast malignancies were diagnosed in our department during the study period of 10 years and the total number of NHLs [Nodal and extra Nodal] was 2632. Thirty [n=30] patients accounting for 1.13% were diagnosed to have lymphomatous involvement of the breast. The Female to Male ratio was13.5:1; age range was 12-92 years with a median age of 43 years [Mean age 46.5 years and Standard deviation of age was 16.88 years]. The sites of the lesions were the right breast in 11 cases [37.93%], left breast in 9 cases [31.03%] and both breasts in 2 cases [6.89%], while the location of 8 masses [27.58%] was unknown. Immunohistochemical studies were negative for cytokeratins [MNF and Cam 5.2] in all cases. All cases of DLBCL expressed B cell lineage antigens and were positive for LCA and Pan B [CD20 and 79a]. We concluded that breast lymphomas represent 1.13% of all NHL and 0.5% of all breast malignancies in this study. The most frequent morphologic type was diffuse large B-cell lymphoma. As patients with primary breast lymphoma have a better prognosis than those with carcinoma of the breast or patients with extranodal lymphomas, a multidisciplinary approach including surgery, radiotherapy, and chemotherapy when needed would result in a more favourable outcome

Capecitabine plus vinorelbine combination therapy in patients with metastatic breast cancer pretreated with anthracyclines and/or taxanes

To determine efficacy and safety of capecitabine plus vinorelbine in metastatic breast cancer [MBC] patients who relapse after adjuvant and/or first line chemotherapy [including anthracyclines and/or taxanes]. From April 2007 to March 2003, 26 eligible patients were recruited. Patients were treated by Vinorelbine in a dose of 25 mg/m[2] administered on days 1 and 8 every 3 weeks with Capecitabine orally twice daily [1000 mg/m[2]] for 14 consecutive days starting on day 1 of the cycle. The median age was 56 years [range 31-67]; ECOG PS 0-1, [9-12]; ER/PR +ve [19]; prior chemotherapy anthracvcyclines/taxanes [26/8]. After chemotherapy the overall response rates were 48% [1 CR and 11PR] [95% confidence interval [CI], 35.9-59.7]. In additional seven patients [28%] showed disease stabilization. The median time to disease progression was seven months and median overall survival was 17.5 months. Myelosuppression was the predominant toxicity. Toxicities included grades III and IV neutropenia in 7 [2 7%] and 3 [11.5%] patients respectively, and only one patient developed febrile neutropenia. Grade III hand-foot syndrome occurred only in One patient. Other nonhematologic toxicities were minimal and manageable. This study demonstrated that capecitabine plus vinorelbine combination was effective and well tolerated in MBC patients even after failure of anthracycline-and/or taxane-containing regimens

A Case of Benign Metastasizing Leiomyoma with Multiple Metastasis to the Soft Tissue, Skeletal Muscle, Lung and Breast

Benign metastasizing leiomyoma (BML) is composed of well-differentiated smooth muscle cells and dense connective tissue. BML affects middle-aged women who have had previous hysterectomies due to a histologically benign-appearing uterine leiomyoma. We report here on a case of BML from the uterine leiomyoma in a 39-year-old woman that involved the soft tissues, skeletal muscles, lungs and breasts. She underwent a hysterectomy for the uterine leiomyoma, double oophorectomy for hormonal ablation and lung wedge resection to confirm the diagnosis. The microscopic findings of the breast and lung tumor were similar to those of the benign uterine leiomyoma. Therefore, we consider that these lesions were breast and pulmonary metastases of the uterine leiomyoma. We report here on a rare case of benign metastasizing uterine leiomyoma that involved the soft tissue, skeletal muscles, lungs and breasts, and we include a review of the relevant literature.

Linfoma no Hodgkin de células B con extensión secundaria a glándula mamaria: Evaluación por imagen / Secondary non-Hodgkin's B-cell lymphoma involving the breast: radiologic imaging

Los linfomas secundarios con afectación de la glándula mamaria, aunque raros, representan el grupo más grande de tumores metastásicos de la mama. El linfoma no Hodgkin primario de la mama es también raro, representando del 1.7%-2.2% de los casos de linfoma no Hodgkin extranodal y del 0.38-0.7% de todos los linfomas no Hodgkin. Aproximadamente 300 casos han sido reportados en la literatura. El aspecto mamográfico ha sido descrito como áreas redondeadas u ovales con densidad aumentada. Las masas mamarias pueden aparecer homogéneas o heterogéneas. Las lesiones pueden ser muy bien definidas y ser confundidas con procesos benignos, esto último más probable en pacientes menores de 35 años de edad. Los hallazgos ultrasonográficos son descritos como masas de márgenes bien definidos con ecos de intensidad baja a moderada. Las paredes posteriores de la masa suelen estar bien definidas, probablemente con ligero reforzamiento acústico pero sin sombra posterior asociada. En resumen, el aspecto mamográfico del linfoma mamario no es específico, pero el diagnóstico puede ser excluido si hay presencia de calcificaciones o reacción desmoplásica. El tejido linfoide prominente en un paciente con masas mamarias debería despertar la sospecha de linfoma mamario. El aspecto más crítico en el estudio de una masa de la mama es la biopsia del tejido, puesto que una lesión linfomatosa tiene radiográficamente patrones indeterminados. Presentamos el caso de una mujer de 79 años con dolor abdominal y una masa palpable en la mama derecha; realizamos un breve resumen de las características clínicas y principales hallazgos por imagen del linfoma no Hodgkin con afección a la glándula mamaria (radiografía de tórax, mastografía, ultrasonido mamario, y tomografía de tórax).

Secondary lymphomas involving the breast, although uncommon, represent the largest group of metastasic tumors to the breast. Primary non-Hodgkin lymphomas (NHLs) of the breast are also rare, accounting for 1.7% to 2.2% of extranodal NHL cases and 0.38 to 0.7% of all NHLs. Approximately 300 cases have been reported in the Medical literature. Mammographic appearances are described as round or oval areas of opacity. The breast mass may appear homogeneous or inhomogeneous. The lesion may be very well defined and may be mistaken for a benign process, most notable in patients younger than 35 years of age. Ultrasonographic appearance is described as a sharply defined mass with low or medium echoes. The posterior aspect of the mass is well defined (possibly with slight acoustic enhancement but with no associated posterior shadowing). In summary, the mammographic appearance of the breast lymphoma is nonspecific, but the diagnosis can possibly be excluded if calcifications or a desmoplastic reaction are present. Prominent lymph vessels in a patient with a breast mass should raise the suspicion of breast lymphoma. The most critical aspect in the workup of a breast mass is the tissue biopsy, since radiographically lymphomatous lesions are indeterminate. We present the case of a 79-year-old woman with abdominal pain and a palpable breast mass; we also make a brief summary of the clinical features and main imaging findings of NHL (plain radiograph, mammography, breast ultrasound and thorax tomography).

Reconstrução Mamária com diferentes abordagens do Retalho TRAM / Mammary reconstruction with tram flap conducted with different approaches

Apresentamos quatro casos de reconstrução mamária onde foram utilizadas variantes do retalho TRAM. Com o objetivo de viabilizar os retalhos, foram realizados procedimentos de autonomização, pré-fabricação e para reduzir a morbidade foi utilizado o retalho vertical. As cirurgias tiveram boa execução, os objetivos de reconstituição estética da mama foram atingidos e todos os casos tiveram boa evolução e não constatamos complicações.

The authors present four cases of the use of tram flap and its variants in mammary reconstruction. The autonomization and prefabricated TRAM were made to enhance flap viability. The Drever or vertical flap was made to reduce morbidity. There were no complications, the aesthetic breast reconstruction goals were achieved, the surgery were well conducted and the clinic cases had good evolution.

Radiologic findings of metastatic signet ring cell carcinoma to the breast from stomach

Two Korean women (41 and 23-years of age) presented with painful breast enlargement and redness. The involved breast was confirmed as metastatic signet ring cell carcinoma. Although metastatic signet ring cell carcinoma of the breast shows similar clinical symptoms to inflammatory breast cancer, the difference between the two is that this malignancy showed no microcalcifications or mass on radiographic findings (mammograms and US). Therefore, after the confirmation of signet ring cell carcinoma of the breast has been made, metastatic signet ring cell carcinoma should be considered if there are no microcalcifications or masses evident on radiographic findings.