scholarly journals Presence of BRCA1 Gene Mutation in Bitches with Malignant Mammary Tumors

2021 ◽  
Vol 49 ◽  
Author(s):  
Camila Calvi Menegassi Ferreira ◽  
Stefhano Luis Cândido ◽  
Luciana Maria Curtio Soares ◽  
Matias Bassinello Stocco ◽  
Andresa De Cássia Martini ◽  
...  

Background: Mammary tumors (MTs) in bitches are similar to breast cancers in women. Thus, they can be used as a model for human breast cancer and findings can be extrapolated for use in human medicine. BRCA1 is a tumor suppressor gene. When the gene has a mutation, it cannot repair damaged DNA, which causes genetic instability and tumorigenesis. Therefore, we aimed to study the frequency of single nucleotide polymorphisms (SNPs) in the BRCA1 gene that are associated with distinct histological types of malignant MT in bitches.Materials, Methods & Results: The study population consisted of 91 bitches, including a control group of 6 animals with healthy mammary glands and 85 animals with MTs. All animals underwent a presurgery evaluation consisting of a questionnaire administered to the person responsible for the animal, a physical examination, collection of peripheral blood for hematological and serum biochemistry evaluations, an electrocardiogram, and a preanesthesia evaluation. In addition, distant metastasis was studied via chest radiography and abdominal ultrasound. After evaluations were complete, the animals that could undergo surgery were administered general anesthesia and underwent a mastectomy or mammary gland sample collection. Histopathological examination and molecular analysis were performed to identify mutations in the BRCA1 gene. Histopathological examinations found 10 different types of malignant tumors in 36 sick animals. Tumor samples plus samples from the 6 control animals were subjected to DNA extraction, polymerase chain reaction (PCR) analysis, and genetic sequencing. The tumor with the highest incidence (33.33%) was a complex carcinoma, followed by carcinoma in mixed tumor (13.88), tubular carcinoma (13.88) and carcinosarcoma (13.88). Molecular analysis revealed 3 different SNP points in 5 samples (4006G>A, 3619A>G, and 3761C>T). The allelic variant 4006G>A (1/36) resulted in the alteration of the amino acid valine by isoleucine (V1336 I). The mutation 3619A>G (2/36) inserted the amino acid alanine instead of threonine (T1207 A). The mutation 3761C>T (2/36) led to the alteration of the amino acid serine by phenylalanine (S1254 F), a mutation for which there are no published reports. The histological types that showed BRCA1mutations were complex carcinoma (1/5), carcinoma in mixed tumor (1/5), papillary carcinoma (1/5) and tubular carcinoma (2/5). Software analysis identified the new SNP (nucleotide 3761) in BRCA1 and 2 points mutations in nucleotides 4006 and 3619 and responsible for genetic instability.Discussion: The development of breast cancer is caused by many endogenous and exogenous factors. The results of our study show that these factors have a greater presence in female, mixed breed, uncastrated, and older dogs, confirming the data in the veterinary literature. In the present study, we found different histological types of malignant breast tumors with mutations in the BRCA1 gene, as other authors have reported. However, we also found the mutation 3761C>T, which, to the best of our knowledge, has not been reported in the literature. This shows the need for studies in veterinary medicine that assess mutations in the BRCA1 gene and the most common histological types. In conclusion, SNPs in the BRCA1 gene cause genetic instability, resulting in additional mutations that lead to the development of breast tumors. They are point mutations that affect transcription, resulting in truncated proteins. These proteins may have a loss of function, leading to carcinogenesis.Keywords: polymorphism, BRCA1 gene, cancer, dogs.Descritores:polimorfismo, gene BRCA1, câncer, cães. Título: Presença da mutação do gene BRCA1 em cadelas com tumores mamários malignos. 

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22174-e22174
Author(s):  
C. Bareggi ◽  
D. Consonni ◽  
B. Galassi ◽  
D. Gambini ◽  
E. Locatelli ◽  
...  

e22174 Background: Uncommon breast tumors are often neglected by large clinical trials, even if their incidence is not so low. Methods: We investigated stage, treatment and outcome of 112 patients affected by uncommon breast cancer, out of 2,185 breast cancer patients diagnosed and followed in our Institution from January 1985 to October 2008. Results: Rare subtypes were represented as follows: tubular 2.7% (58 pts), mucinous 1.1% (25 pts), medullary 1% (21 pts), papillary 0.4% (8 pts). Median age at diagnosis was 56.5 years among patients with tubular histotype, 68.9 years for mucinous, 55 and 61.7 years for medullary and papillary, respectively. Stage I tumors were 87.7% among patients with tubular differentiation, 60% for mucinous, 26.3% for medullary and 50% for papillary, (compared to 45.7% in invasive ductal carcinoma: 1,626 pts). Stage II represented 12.3% among patients with tubular carcinoma, 32% for mucinous, 57.9% for medullary and 37.5% for papillary. Surgical option for stage I and stage II was usually conservative surgery (quadrantectomy, lumpectomy) plus local radiotherapy, followed by estrogenic blockade. In stage III radical mastectomy was often performed, followed by hormonal suppression. Median DFS for patients with tubular cancer was 4.1 years, for mucinous 3.7 years, 10.5 and 5.1 years for medullary and papillary, respectively. Median OS for patients with tubular cancer was 4.3 years, whereas for mucinous 4.2 years, for medullary 11 years and 5.3 years for papillary. Conclusions: In our retrospective analysis, uncommon breast tumors are often diagnosed at limited stages, resulting in good prognosis, with standard treatment. Further studies are warranted for a better management of these diseases. No significant financial relationships to disclose.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22223-e22223
Author(s):  
N. A. Zarubina ◽  
V. D. Petrova ◽  
T. V. Sinkina ◽  
S. A. Terekhova ◽  
A. F. Lazarev ◽  
...  

e22223 Background: Hereditary breast carcinomas that are attributable to BRCA1 mutations have their own morphological and immunohistochemical characteristics. This study was aimed to analyze the level of expression of steroids (estrogen and progesterone) and HER2-neu receptors in BRCA1 associated breast cancer. Methods: DNA patterns from 264 patients with hereditary breast cancers (breast cancer diagnosed at the age under 40; bilateral breast cancer; combination of breast and ovarian cancers; 2 and more breast cancers in blood relatives). All the patients were residents of the Altai Territory. BRCA1 gene mutations were registered in 34 patients (12.9%): 5382insC gene mutation - in 28 patients; 300A/C - in 2 patients; 4153del - in 3 patients; 185del - in 1 patient. The frequency of the BRCA1 5382insC allele mutation was 7.3; 300A/C - 0.52; 4153del - 0.26; 185del - 0.83. Immunohistochemical characteristics of BRCA1-associated breast tumors tissue from these patients were investigated. Results: 32 BRCA1-associated breast carcinomas were estrogen receptor- negative; 1 - week positive (H-score 50–100); 1 - moderate positive (H- score 100–200). 33 BRCA1-associated breast carcinomas were progesterone receptor- negative; 1 - positive (H-score 200 and more). HER2-negative were 31 BRCA1-associated breast carcinomas; 2 were week positive (HER2-neu +); 1 - was moderate positive (HER2-neu ++). Conclusion: BRCA1-associated beast carcinomas have been found to be more frequently estrogen receptor-, progesterone receptor-, and HER2- negative. These data show that hereditary breast cancer associated with BRCA1 gene mutations poses poor prognosis. No significant financial relationships to disclose.


2004 ◽  
Vol 37 (3) ◽  
Author(s):  
LILIAN JARA ◽  
SANDRA AMPUERO ◽  
EUDOCIA SANTIBÁÑEZ ◽  
LORENA SECCIA ◽  
JUAN RODRÍGUEZ ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Lada Dyachenko ◽  
Kristina Havrysh ◽  
Anita Lytovchenko ◽  
Irina Dosenko ◽  
Stepan Antoniuk ◽  
...  

Purpose. To investigate a frequency of antibody response to SEREX-identified medullary breast carcinoma autoantigens ZRF1 and KRR1 in sera of breast cancer patients taking into account clinical and molecular characteristics of tumors for opening of new perspectives in creation of minimally invasive immunological tests for cancer diagnostics. Methods. Enzyme-linked immunosorbent assay and bioinformatics analysis. Results. Increased frequency of antibody response was found in sera of breast cancer patients to ZRF and KRR1 antigens. The antibody response to these antigens was higher in sera of patients with invasive ductal carcinoma than in sera of patients with other histological types of breast tumors. Moreover, more frequent antibody response to ZRF antigen was found in sera of patients with less aggressive tumors. The sequence analysis of ZRF1 antigen SEREX clones obtained from cDNA libraries of different tumors demonstrates that they encode different protein isoforms. Conclusion. Tumor-associated antigens KRR1 and ZRF1 and their cognate autoantibodies could be considered as potential molecular markers of breast cancer which need to be further investigated.


Author(s):  
Hanan Polansky ◽  
Hava Schwab

Most breast cancer cases show a decrease in the concentration of the breast cancer type 1 susceptibility protein (BRCA1). However, only a small portion of these cases have a mutated BRCA1 gene. Although many attempts have been made to identify the reason for the decrease in BRCA1 expression in sporadic, non-heritable breast cancer cases, the cause is still unknown. In this review, we use the Microcompetition Model to explain how certain latent viruses, which are frequently detected in breast cancer tumors, can decrease the expression of the BRCA1 gene and cause the development of breast tumors.


2021 ◽  
Author(s):  
Leonie Ratz ◽  
Chiara Brambillasca ◽  
Leandra Bartke ◽  
Marieke van de Ven ◽  
Natalie Proost ◽  
...  

Abstract Background: The majority of BRCA1-mutant breast cancers are characterized by a triple-negative phenotype (TNBC) and a basal-like molecular subtype, associated with aggressive clinical behavior. Current treatment options are limited, highlighting the need for the development of novel targeted therapies for this tumor subtype. Methods: Our group previously showed that EZH2 is functionally relevant in BRCA1-deficient breast tumors and blocking EZH2 enzymatic activity could be a potent treatment strategy. To validate the role of EZH2 as a therapeutic target and to identify new synergistic drug combinations, we performed a high-throughput drug combination screen in various cell lines derived from BRCA1-proficient and deficient - mouse mammary tumors. Results: We identified the combined inhibition of EZH2 and the proximal DNA damage response kinase ATM as a novel synthetic lethality-based therapy for the treatment of BRCA1-deficient breast tumors. We show that the combined treatment with the EZH2 inhibitor GSK126 and the ATM inhibitor AZD1390 led to reduced colony formation, increased genotoxic stress, and apoptosis-mediated cell death in BRCA1-deficient mammary tumor cells in vitro. These findings were corroborated by in vivo experiments showing that simultaneous inhibition of EZH2 and ATM significantly increased anti-tumor activity in mice bearing BRCA1-deficient mammary tumors. Conclusion: Taken together, we identified a synthetic lethal interaction between EZH2 and ATM and propose this synergistic interaction as a novel molecular combination for the treatment of BRCA1-mutant breast cancer.


2003 ◽  
pp. 153-159 ◽  
Author(s):  
E J S√°nchez-Barcel√≥ ◽  
S Cos ◽  
R Fern√°ndez ◽  
M D Mediavilla

Melatonin is an indolic hormone produced mainly by the pineal gland. The former hypothesis of its possible role in mammary cancer development was based on the evidence that melatonin down-regulates some of the pituitary and gonadal hormones that control mammary gland development and which are also responsible for the growth of hormone-dependent mammary tumors. Furthermore, melatonin could act directly on tumoral cells, as a naturally occurring antiestrogen, thereby influencing their proliferative rate. The first reports revealed a low plasmatic melatonin concentration in women with estrogen receptor (ER)-positive breast tumors. However, later studies on the possible role of melatonin on human breast cancer have been scarce and mostly of an epidemiological type. These studies described a low incidence of breast tumors in blind women as well as an inverse relationship between breast cancer incidence and the degree of visual impairment. Since light inhibits melatonin secretion, the relative increase in the melatonin circulating levels in women with a decreased light input could be interpreted as proof of the protective role of melatonin on mammary carcinogenesis. From in vivo studies on animal models of chemically induced mammary tumorigenesis, the general conclusion is that experimental manipulations activating the pineal gland or the administration of melatonin lengthens the latency and reduces the incidence and growth rate of mammary tumors, while pinealectomy usually has the opposite effects. Melatonin also reduces the incidence of spontaneous mammary tumors in different kinds of transgenic mice (c-neu and N-ras) and mice from strains with a high tumoral incidence. In vitro experiments, carried out with the ER-positive MCF-7 human breast cancer cells, demonstrated that melatonin, at a physiological concentration (1 nM) and in the presence of serum or estradiol: (a) inhibits, in a reversible way, cell proliferation, (b) increases the expression of p53 and p21WAF1 proteins and modulates the length of the cell cycle, and (c) reduces the metastasic capacity of these cells and counteracts the stimulatory effect of estradiol on cell invasiveness; this effect is mediated, at least in part, by a melatonin-induced increase in the expression of the cell surface adhesion proteins E-cadherin and beta(1)-integrin. The direct oncostatic effects of melatonin depends on its interaction with the tumor cell estrogen-responsive pathway. In this sense it has been demonstrated that melatonin down-regulates the expression of ERalpha and inhibits the binding of the estradiol-ER complex to the estrogen response element (ERE) in the DNA. The characteristics of melatonin's oncostatic actions, comprising different aspects of tumor biology as well as the physiological doses at which the effect is accomplished, give special value to these findings and encourage clinical studies on the possible therapeutic value of melatonin on breast cancer.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Marie Alfrede Mvondo ◽  
Marius Trésor Wego Kamgaing ◽  
Sylvie Léa Wansi Ngnokam

Breast cancer is the most common estrogen-dependent cancer in the world. Hormone therapy for this cancer can be neoadjuvant and/or adjuvant. Herbal remedies with antiproliferative properties are believed to be potential anticancer agents. The aqueous extract of Dacryodes edulis (Burseraceae) leaves (AE), a medicinal plant used against cancer in Cameroon, was found to display antiproliferative effects in ovariectomized rats. Compounds isolated from this plant exhibited anticancer activity in vitro. To determine whether AE has an anticancer potential, its effects were investigated in rats with already developed breast cancer. Mammary tumors were induced by a single subcutaneous administration (under the mammary gland) of 7,12-dimethylbenz[a]anthracene (DMBA; 50 mg/kgBW) to immature female rats. After 22–26 weeks of observation, animals with palpable tumors were treated with tamoxifen (3.3 mg/kgBW) and AE at doses of 25 and 100 mg/kgBW. The negative control received distilled water. Treatments were given orally for 21 consecutive days. The volume of mammary tumors was evaluated weekly using a caliper. On day 22, animals were sacrificed. Cholesterol and estradiol levels were assessed in serum, breast tumors, mammary glands, and ovaries. Oxidative status of tumors was evaluated. The histological analysis of mammary glands and breast tumors was performed. Results showed that AE reduced tumor volume and weight ( p < 0.05 ). This effect was associated with reduced cholesterol ( p < 0.001 ) and estradiol ( p < 0.01 ) levels in breast tumors, serum, ovaries, and mammary glands. AE also increased tumors levels of malondialdehyde ( p < 0.05 ) and antioxidant enzymes ( p < 0.01 ). These effects contributed to the decrease in the size of breast alveoli ( p < 0.01 ), the density of cancer cells in breast tumors, and the invasion of these cells into the tumor connective tissue. In conclusion, the aqueous extract of D. edulis leaves, thanks to its ability to inhibit tumor growth, could be considered as a potential alternative for the neoadjuvant treatment of estrogen-dependent breast cancer.


2020 ◽  
Vol 48 ◽  
Author(s):  
Paula Elisa Brandão Guedes ◽  
Hannah Bandeira Thame Daniel ◽  
Kátia Moema Oliveira Rosa Sampaio ◽  
Elizângela Barboza da Silva ◽  
Manoel Luiz Ferreira ◽  
...  

Background: Mammary neoplasms in dogs are commonly observed in veterinary clinical routine, most of which being malignant. Hormonal stimulation, endogenous or exogenous, may possibly influence its development. In addition to clinical evaluation, ultrasound analysis can provide information about the characteristics of breast lumps. The association between clinical-epidemiological and pathological data is important for diagnosis. Therefore, given the importance of this pathology for the health of affected dogs, we aimed to evaluate the clinical and ultrasound alterations, along with the factors associated with the development of benign and malignant mammary neoplasms in female dogs. Materials, Methods & Results: We examined 47 samples from the mammary tumors of 35 female dogs at the Small Animal Clinic of the Veterinary Hospital (HV) of the Santa Cruz State University (UESC). The dogs underwent a complete clinical examination, with clinical staging, via TNM classification, followed by hematological, biochemical, radiological and ultrasound, abdominal, and breast exams. Breast ultrasound examination was used to evaluate the shape parameters such as, limits, margins or contour, ecotexture, echogenicity, hyperechoic halo, posterior acoustic shading, surrounding changes, and nodule components. These criteria were associated with the histopathological classification of neoplasms. Epidemiological data was studied through an adapted questionnaire containing information on risk factors associated with breast cancer. The same questionnaire was applied to tutors of 19, age-matched, female dogs with no history of breast cancer. The results revealed that most female dogs with neoplasia were over eight years of age, with no specific breed and were not castrated, and 31.4% of them had already been administered with contraceptives during the reproductive period. Ovariohysterectomy acted as a protective factor (OR 0.06) to the development of breast tumors, while contraceptive use was considered as a risk factor (OR 6.99). The average time reported between tumor perception and clinical care was 13.2 months. The caudal and inguinal abdominal breasts were the most affected. Among the samples evaluated, 76.6% were malignant, with mixed tumor carcinoma being the most frequent type and 69.4% graded in grade I. Nodules classified as malignant showed the largest diameter (P < 0.05). Breast ultrasound results revealed that tumors with heterogeneous echotextures and mixed components were associated with malignancy (P < 0.05). Discussion: The fact that the average age of female dogs with breast cancer was over eight years of age corroborates the literature. Considering that a greater age would mean a longer exposure to the carcinogenic initiators responsible for mutations, and to promoters, such as hormonal changes. Contraceptives increase the risk of breast lumps, while reduce that of ovariohysterectomy, in female dogs, even when performed after the second heat. The size of the nodules and ultrasound criteria related to echotexture and the type of component of the neoplasia may be used as prognostic parameters of female breast nodules. Additionally, most nodules evaluated in this study were malignant (mixed tumor carcinoma was the most common subtype), possibly due to the owners' delay in seeking veterinary care after tumor observation. Although malignant, most nodules presented with a low histopathological grading.Background: Mammary neoplasms in dogs are commonly observed in veterinary clinicalroutine, most of which being malignant. Hormonal stimulation, endogenous or exogenous,may possibly influence its development. In addition to clinical evaluation, ultrasound analysiscan provide information about the characteristics of breast lumps. The association betweenclinical-epidemiological and pathological data is important for diagnosis. Therefore, given theimportance of this pathology for the health of affected dogs, we aimed to evaluate the clinicaland ultrasound alterations, along with the factors associated with the development of benignand malignant mammary neoplasms in female dogs.Materials, Methods &amp; Results: We examined 47


2020 ◽  
pp. 25-31
Author(s):  
M. L. Mazo ◽  
O. E. Jacobs ◽  
O. S. Puchkova ◽  
M. V. Feldsherov ◽  
E. V. Kondratyev

The rate of detection of breast cancer by MRI, while other methods of radiological diagnosis are not sufficiently informative, ranges from 5.2 to 26.3 per cent. Suspicious breast tumors of category BI-RADS 4, 5 show morphological image-guided biopsy verification, in particular MRI with contrast. Purpose. To show the possibilities and features of carrying out MRI-guided vacuum breast biopsy, including after aesthetic breast augmentation. Material and methods. A comprehensive X-ray, ultrasound and MRI examination of 54 women aged between 28 and 70 years with different breast tumors was conducted. Of these, five were detected only by breast MRI with contrast, and were morphologically verified by MRI-guided vacuum aspiration biopsy. Results. 14 of the 54 patients with breast mass were diagnosed with breast cancer and 26 were diagnosed with benign diseases. The effectiveness of comprehensive examination and low-invasive high-tech MRI-guided procedures in early refined screening for breast cancer, including after aesthetic breast augmentation, has been demonstrated. MRI-guided vacuum-assisted breast biopsy is a fast, safe and accurate diagnostic method of morphological verification of suspicious breast tumors that do not have X-ray and ultrasound.


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