Biological Behavior Of Breast Cancer Research Articles

Intraductal Therapy in Breast Cancer: Current Status and Future Prospective.

With our improved understanding of the biological behavior of breast cancer, minimally invasive intervention is urgently needed for personalized treatment of early disease. Intraductal therapy is one such minimally invasive approach. With the help of appropriate tools, technologies using the intraductal means of entering the ducts may be used both to diagnose and treat lesions in the mammary duct system with less trauma and at the same time avoid systemic toxicity. Traditional agents such as those targeting pathways, endocrine therapy, immunotherapy, or gene therapy can be used alone or combined with other new technologies, such as nanomaterials, through the intraductal route. Additionally, relevant mammary tumor models in rodents which reflect changes in the tumor microenvironment will help deepen our understanding of their biological behavior and heterogeneity. This article reviews the current status and future prospects of intraductal therapy in breast cancer, with emphasis on ductal carcinoma in situ.

Effects of CCL5 on the biological behavior of breast cancer and the mechanisms of its interaction with tumor‑associated macrophages.

The recurrence and metastasis of breast cancer limit the effectiveness of clinical treatments, making them important issues for clinicians to address. Tumor-associated macrophages (TAMs) contribute to regulating the immune system. C-C motif chemokine ligand 5 (CCL5) is an inflammatory chemokine that promotes chemotaxis on cells involved in the immune/inflammatory response. Breast cancer cells that secrete CCL5 act on THP-1 cells, influencing the invasion and metastasis of tumors. However, knowledge remains limited regarding the mechanism underlying the effects of CCL5 on breast cancer cells and TAMs, as well as the mechanisms promoting the migration and invasion of breast cancer. The present study demonstrated that the positive expression of CCL5 was associated with lymph node status and tumor-node-metastasis stage. Treatment with ≥20 ng/ml CCL5 significantly promoted the migration and invasion of MCF-7 and MDA-MB-231 cells. CCL5-small interfering RNA intervention significantly decreased the migration and invasion of the two cell types. In vitro, THP-1 cells were successfully induced to become TAMs, which were then recruited via the chemotactic effects of CCL5. This process was achieved through the co-stimulation of phorbol-12-myristate-13- acetate, interleukin-4 (IL-4) and IL-13. The nuclear factor-κB (NF-κB) signaling pathway was activated to regulate EMT, as well as the migration and invasion process of MCF-7 cells, when co-cultured with TAMs. We also reported that blocking the expression of CCL5 in vivo may significantly inhibit the growth of human breast cancer xenografts. Therefore, targeting CCL5 may be considered as a novel therapeutic strategy for suppressing the invasion and metastasis of breast cancer.

Retrospective study of clinico-pathological features of breast cancer patients in young women (

BACKGROUND: Differences in the clinical and biological characteristics between young and older breast cancer patients have been observed in many cancer centres.Breast cancer in younger women may be more aggressive in their behaviour and more advanced at their initial presentation in younger patients.There is a paucity of data on breast cancer in younger women in India.The literature from the Indian subcontinent in this regard is scanty, and therefore in this study we particularly focused on the clinical, biological behavior of breast cancer in younger women.

RAP80 expression in breast cancer and its relationship with apoptosis in breast cancer cells.

BackgroundRAP80 is a member of BRCA1-A complex, which plays an important role in regulating the cell cycle checkpoint and DNA damage repair in the nucleus.MethodWe investigated RAP80 expression in breast cancer and its paired normal breast tissues to further analyze its role in the biological behavior of breast cancer cells.ResultsRAP80 expression in breast cancer (62.3%, 101/162) was significantly lower than that in adjacent normal breast tissues (P<0.05). RAP80 expression was related to tumor size, lymph node metastasis, TNM stage, and molecular subtype (P<0.05). RAP80 mRNA expression was significantly lower in triple-negative breast cancer than other types. The mRNA and protein of RAP80 were obvious in MCF-7 and very weak in ZR-75 or MDA-MB-231, so we picked MCF-7 to be transfected with RAP80 siRNA. The survival rate of both cells decreased in a dose-dependent manner and the IC50 value for cisplatin in MCF-7 RAP80 siRNA cells was 0.83 µg/mL, and 1.69 µg/mL in wild-type MCF-7 according to MTT. RAP80 siRNA transfection upregulated the apoptosis and downregulated invasive or migrating ability of MCF-7. RAP80 siRNA also upregulated the protein expression of Caspase-3, cleaved Caspase-3, Apaf-1, Cytochrome C, Bax, and Fas, and downregulated the protein expression of Bcl-2.ConclusionRAP80 expression was related to ER or PR activity. Inhibition of RAP80 expression can induce apoptosis in breast cancer cells and improve chemosensitivity to cisplatin. Tumor cells can activate protective responses to inhibit cell cycle progression, which may be related to RAP80, and repair cisplatin-induced DNA damage. RAP80 is related to BRCA1’s effect, which can be used as an interesting target for pharmacological modulation that can increase the efficiency of cisplatin chemotherapy.

PTEN and SHIP: Impact on lymphatic metastasis in breast cancer.

Lymph node metastasis is the most common form of metastasis in breast cancer and a crucial indicator influencing breast cancer treatment results. The biological process of lymph node metastasis involves deficiency and mutation of tumor suppressor genes. PTEN and SHIP are critical indicators used to detect occurrence, development, invasion, and metastasis of breast cancer. Loss of expressions of PTEN and SHIP may contribute to lymphatic metastasis of breast cancer, so they can be used as objective indicators for judging the biological behavior of breast cancer. In this study, we perform a comprehensive analysis to investigate the effect of PTEN and SHIP gene expression on regulating lymph node metastasis in breast cancer.

MicroRNA-223 Targeting STIM1 Inhibits the Biological Behavior of Breast Cancer

Background/Aims: To investigate the cellular effects and clinical significance of microRNA-223 (miR-223) in breast cancer by targeting stromal interaction molecule1 (STIM1). Methods: Breast cancer cell lines (T47D, MCF-7, SKB-R3, MDA-MB-231 and MDA-MB-435) and a normal breast epithelial cell line (MCF-10A) were prepared for this study. MiR-223 mimics, anti-miR-223 and pcDNA 3.1-STIM1 were transiently transfected into cancer cells independently or together, and then RT-qPCR was performed to detect the expressions of miR-223 and STIM1 mRNA, dual-luciferase reporter assay was conducted to examine the effects of miR-223 on STIM1, Western blotting was used to measure the expressions of the STIM1 proteins, MTT and Trans-well assays were performed to detect cell proliferation and invasion. Finally, the correlation of miR-223 and STIM1 was investigated by detecting with ISH and IHC in breast cancer specimens or the corresponding adjacent normal tissues. Results: Compared with normal cells and tissues, breast cancer tissues and cells exhibited significantly lower expression of miR-223, but higher expression of STIM1. MiR-223 could inhibit the proliferation and invasiveness of breast cancer cells by negatively regulating the expressions of STIM1. Reimplantation with STIM1 partially rescued the miRNA-223-induced inhibition of breast cancer cells. Clinical data revealed that high expression of STIM1 and miR-223 was respectively detrimental and beneficial factor impacting patient’s disease-free survival (DFS) rather than overall survival (OS). Moreover, Pearson correlation analysis also confirmed that STIM1 was inversely correlated with miR-223. Conclusion: MiR-223 inhibits the proliferation and invasion of breast cancer by targeting STIM1. The miR-223/STIM1 axis could possibly be a potential therapeutic target for treating breast cancer patients.

Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions.

In recurrent breast cancer, the tumor phenotype, as assessed by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status, occasionally changes. This change, in addition to the Ki67 index were evaluated at sites of recurrence and the correlation between changes in tumor phenotype and survival were assessed in breast cancer patients. Comparisons in pathological parameters between primary and metastatic lesions were drawn between ER, PR, HER2, and the Ki67 index in 70 patients with recurrent breast cancer. The association between changes in tumor phenotype and patient survival was assessed. The hormone receptor status changed from positive, in the primary lesions, to negative, in the metastatic lesions in 19.8% (ER) and 39.5% (PR) of patients, respectively. Conversion from negative to positive status was confirmed in 27.2% (ER) and 31.2% (PR) of patients, respectively. A change in HER2 status from negative (primary lesion) to positive (metastatic lesion) occurred in seven patients (10%). The mean Ki67 index of primary lesions with positive hormone receptor status was significantly lower than at sites of recurrence with any hormone receptor status, from 10.9±9.8 standard deviation (SD) to 22.9±18.6 (P=0.031) and 12.2±10.5 SD to 27.4±20.9 (P=0.023), for ER and PR, respectively. The mean overall survival of patients with ER status conversion from positive to negative was 7.4±1.2 standard error (SE) years, and 14.8±1.4 SE years for patients who retained positive ER status (P=0.005, log-rank), with a hazard ratio of 3.44 (95% confidence interval, 1.36-8.33). This difference in survival based upon change in ER status was similarly observed in patients with PR status conversion in the same direction. Thus, ER and PR status conversion at the time of recurrence strongly impact survival, particularly if the change is from positive (primary lesion) to negative (metastatic lesion). Monitoring the biological behavior of breast cancer may benefit a patient by allowing for a novel personalized treatment strategy.

Identification of prognostic collagen signatures and potential therapeutic stromal targets in canine mammary gland carcinoma.

Increasing evidence indicates that the tumor microenvironment plays a critical role in regulating the biologic behavior of breast cancer. In veterinary oncology, there is a need for improved prognostic markers to accurately identify dogs at risk for local and distant (metastatic) recurrence of mammary gland carcinoma and therefore would benefit from adjuvant therapy. Collagen density and fiber organization have been shown to regulate tumor progression in both mouse and human mammary tumors, with certain collagen signatures predicting poor outcomes in women with breast cancer. We hypothesized that collagen signatures in canine mammary tumor biopsies can serve as prognostic biomarkers and potential targets for treatment. We used second harmonic generation imaging to evaluate fibrillar collagen density, the presence of a tumor-stromal boundary, tumor associated collagen signatures (TACS) and individual collagen fiber characteristics (width, length and straightness) in grade I/II and grade III canine mammary tumors. Collagen density, as well as fiber width, length and straightness, were inversely correlated with patient overall survival time. Notably, grade III cases were less likely to have a tumor-stromal boundary and the lack of a boundary predicted poor outcome. Importantly, a lack of a defined tumor-stromal boundary and an increased collagen fiber width were associated with decreased survival even when tumor grade, patient stage, ovariohysterectomy status at the time of mammary tumor excision, and histologic evidence of lymphovascular invasion were considered in a multivariable model, indicating that these parameters could augment current methods to identify patients at high risk for local or metastatic progression/recurrence. Furthermore, these data, which identify for the first time, prognostic collagen biomarkers in naturally occurring mammary gland neoplasia in the dog, support the use of the dog as a translational model for tumor-stromal interactions in breast cancer.

Breast cancer in young women: A retrospective study from tertiary care center of north India.

Aim:Breast cancer is the most common cause of cancer in women worldwide. They have more aggressive clinical behaviour with poor outcomes in younger patients. The aim of this study was to evaluate the impact of age on prognosis of breast cancer in women above and under 40 years of age.Material and Methods:Medical record of 415 patients with invasive breast cancer were analysed from January 2011 to December 2014 in our department. The last was done in December 2015. All cases diagnosed with breast cancer stages I to IV were evaluated, and grouped on the basis of age [less than 40 and above 40 years]. Baseline categorical variables were analysed using the Chi-square test or Fisher's exact test. Non categorical variable were analysed using t-test.Result:A total of 372 patients were reviewed because 42 patients defaulted. The median age at the time of diagnosis was 44.6 years (range 23 to 90 years). Metastasis to distant organs were more in women with age <40. Tumour relapse occurred in 131 cases, among which 84 cases died, 35 patients (26.31%) in less than 40 group vs. 49 patients (20.50%) in above 40 groups. The estimated median OS in the two groups are 32 and 41 months respectively.Conclusion:The biological behaviour of breast cancer in younger age group has been shown to be associated with aggressive nature and has a worse clinical outcome as compared to that in older group.

Distribution of Breast Cancer Biomarkers by Age in Iran

Background and Objectives: Breast cancer is the leading cause of cancer related death globally and presents as the most common female malignancy in Iran. Multiple factors are associated with an increased risk of developing breast cancer; for example first degree family history of breast cancer, BRCA1, 2 mutation and history of atypical hyperplasia on biopsy are the most important risk factors for developing breast cancer. Some prognostic factors are classically used that it would help us to either choosing recommended optimal treatment or recognizing the prognosis. In several studies it is shown that these factors have different patterns in age groups or histopathologic types. The aim of this study was to determine the age distribution of hormone receptors and biomarkers and determine their relation to the histopathologic types. Methods: Data were gathered from the medical records of Baqiyatallah hospital, Tehran, Iran. Breast cancer patients whose disease was confirmed by pathologic studies and had immunohistochemical profile, were included. Estrogen receptor (ER), Progesterone receptors (PR), HER2/neu and p53 were selected as biomarkers of this study. Results: Mean age of patients was 49.47±12.50 years (range 20 to 86). The most common histopathologic type was invasive ductal carcinoma. Distribution of ER and PR against age detected similar; ER positivity increased with age and it peaked in fifth decade of life, and PR positivity showed more regular pattern and it also peaked in fifth decade of life (p &lt;0.05) HER2/neu positivity also had trend to increase with age and it peaked in sixth decade of life, but P53 had trend to show unimodal distribution pattern that peaked in sixth decade of life, but this findings were not statistically significant (p&gt;0.05). Conclusions: Our breast cancer patients were generally younger than patients round the world. The different distribution pattern of biomarkers in our studies in comparison with similar studies, may suggest different biologic behavior of breast cancer in our patients. Further studies will help illuminate this point.

Expression and clinical significance of moesin and E-cadherin in invasive carcinoma of breast, no specific type

To investigate the correlation of moesin and E-cadherin with biological behavior of breast cancer and its mechanism by comparing expression of moesin and E-cadherin in breast invasive carcinoma of no specific type(BIC-NST), breast ductal carcinoma in situ(BDCIS) and normal breast tissues adjacent to carcinoma. Breast cancer cases of the Huizhou Municipal Center People Hospital were collected between Jan 2008 and Dec 2010, expression of moesin and E-cadherin in 104 cases of BIC-NST, 84 cases of BDCIS and 53 cases of normal breast tissues adjacent to carcinoma were detected by tissue-microarray and SP immunohistochemical staining. Western blot was used to detect moesin expression of 16 BIC-NST fresh tissues. Expression rate of moesin in BIC-NST and BDCIS were significantly higher than normal tissues(P<0.01), but the expression rate of E-cadherin in BIC-NST and BDCIS were significantly lower than those of normal tissues(P<0.01). Expression rate of moesin in BIC-NST grade Ⅲ group was significantly higher than that of the grade Ⅰ group.There was a significantly positive correlation between histological grade and moesin expression(P<0.05). However, E-cadherin expression rate in BIC-NST grade Ⅲ group was significantly lower than that in grade Ⅰ group , and there was a significantly negative correlation between histological grade and E-cadherin expression(P<0.05). Moreover, no significant correlation was observed between moesin and E-cadherin expression in BDCIS tissues. Expression of moesin in clinical stage Ⅱ + Ⅲ BIC-NST was significantly higher than that in stage Ⅰ(P<0.01) . Expression of moesin was significantly associated with lymph node metastasis (P<0.01). But no significant correlation was observed between moesin expression and age, tumor size and vascular invasion . However, expression of E-cadherin in clinical stage Ⅱ+ Ⅲ BIC-NST was significantly lower than that in stage Ⅰ(P<0.01). Expression of E-cadherin was significantly associated with lymph node metastasis and vascular invasion (P<0.01). But no significant correlation was observed between E-cadherin expression, age and tumor size. There was a negative correlation between expression of moesin and E-cadherin in BIC-NST(P=0.021)and BDCIS(P=0.032). Higher moesin and lower E-cadherin signal transduction is closely related to the recurrence and development of breast carcinoma, therefore moesin and E-cadherin might provide new targets for gene therapy in breast carcinoma.

Relationship between p16, p27 proteins and clinicopathological characteristics of breast cancer and their prognostic value

Objective To study the relationship between p16, p27 proteins and clinicopathological characteristics of breast cancer and their prognostic value. Methods p16 protein and p27 protein were detected by two step immunohistochemical method in 93 tissues of breast cancer. Results The positive rates of p16 protein and p27 protein were 46.2 % (43/93) and 54.8 % (51/93). The positive rate of p16 protein in different tumor location (left/right), the maximal diameter and histological type had no statistically significant difference (all P > 0.05), but in the different age groups and axillary lymph node metastasis, the differences were statistically significant (both P 0.05), but was correlated with the infiltration and axillary lymph node metastasis (both P < 0.05). Conclusions The negative expression of p16 and p27 is significantly related with the biological behaviors of breast cancer. Detection of both p16 protein and p27 protein may play an important role in predicting the prognosis of breast cancer. Key words: Breast neoplasms; Immunohistochemistry; p16; p27; Prognosis

Low spinophilin expression enhances aggressive biological behavior of breast cancer.

Spinophilin, a putative tumor suppressor gene, has been shown to be involved in the pathogenesis of certain types of cancer, but its role has never been systematically explored in breast cancer. In this study, we determined for the first time the expression pattern of spinophilin in human breast cancer molecular subtypes (n = 489) and correlated it with survival (n = 921). We stably reduced spinophilin expression in breast cancer cells and measured effects on cellular growth, apoptosis, anchorage-independent growth, migration, invasion and self-renewal capacity in vitro and metastases formation in vivo. Microarray profiling was used to determine the most abundantly expressed genes in spinophilin-silenced breast cancer cells. Spinophilin expression was significantly lower in basal-like breast cancer (p<0.001) and an independent poor prognostic factor in breast cancer patients (hazard ratio = 1.93, 95% confidence interval: 1.24 -3.03; p = 0.004) A reduction of spinophilin levels increased cellular growth in breast cancer cells (p<0.05), without influencing activation of apoptosis. Anchorage-independent growth, migration and self-renewal capacity in vitro and metastatic potential in vivo were also significantly increased in spinophilin-silenced cells (p<0.05). Finally, we identified several differentially expressed genes in spinophilin-silenced cells. According to our data, low levels of spinophilin are associated with aggressive behavior of breast cancer.

Relationship of annexin A2 and osteopontin expression and biological behaviors of breast cancer

Objective To investigate the expression of Annexin A2 and Osteopontin (OPN) in breast cancer tissues and its relationship with pathogenesis of breast cancer.Methods The expression of Annexin A2 and OPN was examined by using immunohistochemical method in 50 cases of human breast cancer tissues and non-cancerous adjacent breast tissues (5 cm away from the margin of breast cancer).Results The positive expression rate of Annexin A2 in breast cancer tissues was 82.00％,and that in non-cancerous adjacent breast tissues was 36.00％ (P ＜0.01).The overexpression of Annexin A2 was related to histologic grade,TNM stage and lymph node metastasis (P ＜ 0.05).The positive expression rate of OPN in breast cancer tissues was 74.00％,and that in non-cancerous adjacent breast tissues was 22.00％ (P ＜ 0.01).The expression of OPN was closely related with TNM stage and lymph node metastasis of breast cancer (P ＜ 0.05).Conclusion The overexpression of Annexin A2 and OPN might be correlated with the biological behaviors of breast cancer. Key words: Annexin A2 ; Osteopontin ; Breast carcinoma

Role of maximum standardized uptake value in fluorodeoxyglucose positron emission tomography/computed tomography predicts malignancy grade and prognosis of operable breast cancer: a multi-institute study

The malignant biological behavior of breast cancer remains obscure on diagnostic images, although understanding the grade of such malignancy is important for selecting appropriate treatment. Therefore, malignancy grades in operable breast cancer were evaluated using positron emission tomography/computed tomography (PET/CT) in a multicenter setting. We prospectively examined the features and prognosis of 344 patients (mean age ± SD: 58.0 ± 12.5 years) with clinical stages I–III breast cancer, who underwent surgical intervention without induction therapy between January 2006 and December 2011. Maximum standardized uptake values (maxSUV) obtained from whole-body fluorodeoxyglucose-PET/CT immediately before surgery were assessed to predict the malignant aggressiveness of tumors including the recurrence-free survival of the patients. Variations in maxSUV among institutions, which are limitations of PET assessments in multicenter studies, were adjusted using a phantom study. The median follow up period was 52 months. The patients were divided into groups according to cut-off maxSUV (≤3.0 vs. >3.0) values established from receiver operating characteristic analysis of recurrence (area under the curve = 0.713). A higher maxSUV was significantly associated with a higher T-factor (p < 0.0001), N-factor (p = 0.0049), nuclear grade (p < 0.0001), negative for estrogen (p = 0.0309), and progesterone receptors (p = 0.0063), positive for human epidermal growth factor receptor 2 (p = 0.0012), lymph node metastasis (p = 0.0128), and vascular invasion (p = 0.0110). Multivariate analysis using Cox proportional hazard regression model revealed high maxSUV and negative estrogen receptor status as significantly prognostic factors (p = 0.033 and p = 0.004, respectively). This study demonstrated that maxSUV on PET/CT as well as estrogen receptor status is useful to predict malignancy grades and the prognosis of patients with breast cancer.

Role of NF-κB as a Prognostic Marker in Breast Cancer : A Pilot Study in Indian Patients

The nuclear factor κB (NF-κB) is a superfamily of transcription factors. It plays an important role in development & progression of cancer. This study was conducted in a tertiary care centre to investigate the significance of NF-κB as a prognostic marker in breast cancer and study its relation with established prognostic markers such as tumor grade, lymph node status, hormone receptor & HER-2/neu expression. We measured NF-κB expression of breast cancer tissue as a test sample & from fibroadenoma as a control. Measurement was done by Western Blot Technique using p65 protein of NF-κB super family of transcription factors. ER,PR and HER-2/neu were measured by immunohistochemistry methods. NF-κB/p65 is significantly associated with large tumor size (≥5cm), high grade tumors, negative ER, negative PR, positive HER-2/neu and high NPI (≥5.4) scores. NF-κB/p65 expression implies aggressive biological behaviour of breast cancer & this study validates significant association of NF-κB /p65 overexpression with large tumor size, negative estrogen & progesterone receptor status and overexpression of c-erbB2 oncoprotein.

Clinical implications of Girdin and PI3K protein expression in breast cancer

The aim of this study was to investigate the correlation between Girdin and PI3K in breast cancer stem cells and the clinical implications of the co-expression of these two proteins in breast cancer patients. CD44+/CD24− tumor cells from the MD-231 cell line were sorted by flow cytometry. The expression status of Girdin and PI3K proteins was detected using western blotting and immunohistochemical staining. The relationship between Girdin and PI3K proteins and clinicopathological parameters was analyzed in 820 breast cancer patients. Girdin and PI3K proteins were more highly expressed in CD44+/CD24− tumor stem cells compared to the control group and Girdin and PI3K proteins were co-immunoprecipitated in the MD-231 cell line. Of the 820 enrolled breast cancer patients, Girdin and PI3K proteins were expressed in 295 (35.98%) and 492 (60.00%) cases, respectively. There were 162 (19.76%) cases which co-expressed Girdin and PI3K proteins. Univariate and multivariate analyses indicated that the co-expression of Girdin and PI3K proteins correlated with histological type, metastatic nodes and distant metastasis (P=0.01, 0.001 and 0.001, respectively). After analyzing survival rates, cases with Girdin and PI3K co-expression were shown to attain a significantly increased distant metastasis rate and poorer postoperative, disease-specific survival compared to those with Girdin and PI3K co-expression (P=0.001). In the Cox regression test, Girdin and PI3K co-expression was detected as an independent prognostic factor (P=0.001). Girdin may regulate the biological behavior of breast cancer via the PI3K/Akt/mTOR pathway, and thus, serve as a potential new target for breast cancer treatment.

Assessing the Role of Ultrasound in Predicting the Biological Behavior of Breast Cancer

The purpose of this article is to correlate various ultrasound features of breast cancer with tumor grade, and with estrogen, progesterone, and ERRB2 (formerly HER2) receptor status as well as to assess the predictive value of these features. The features of breast cancers found by using ultrasound between January 2010 and June 2011 were reviewed for tumor size, margins, and posterior acoustic features. The tumor margins were classified into spiculated, angular, indistinct, lobulated or microlobulated, and circumscribed. The posterior acoustic features were classified into shadowing, enhancement, mixed pattern, and no change. The individual features were correlated with the estrogen receptor (ER)-progesterone receptor (PR) and ERRB2 receptor status and tumor grade. Among 160 patients with breast cancer, 102 (63.8%) were ER-positive/PR-positive, 32 (20.0%) were ER-positive/PR-negative, and 26 (16.3%) were ER-negative/PR-negative (22 were triple-negative). Tumors with posterior shadowing have greater than nine times the odds of having ER-positive findings (95% CI, 2.09-40.81; p = 0.011) and greater than 13 times the odds of having a lower-grade tumor (I or II vs III; 95% CI, 4.90-36.54; p < 0.001) than those without posterior shadowing. Tumors with posterior enhancement have greater than eight times the odds of having at least one negative receptor (95% CI, 3.97-18.11; p < 0.001) and 24 times the odds of having a high-grade tumor (95% CI, 9.91-58.14; p < 0.001) than those without posterior enhancement. The presence of posterior shadowing is strongly associated with an ER-positive and low-grade tumor, whereas the presence of posterior enhancement is strongly associated with a high-grade tumor and with moderate risk of being receptor negative.

Spontaneous Mammary Carcinomas in Female Dogs: Association between the Immunohistochemical Degree of Aggressiveness of Tumors, Intensity of DNA Damage and Residues of Pyrethroids

Diagnosis and biological behavior of breast cancer of female dog represent one of the biggest challenges facing the Veterinarian in recent years. Due to its exponential growth and the degree of aggressiveness, the exact cause of this tumor is probably multifactorial and it is believed that may suffer influence from environmental factors. Among the suspected environmental contaminants are the pyrethroids. Aiming to investigate the participation of pyrethroids in tumorigenesis in female dogs, a study was conducted using 50 female dogs, 22 were positive for simple breast carcinoma (Group I), 18 with a diagnosis of complex breast carcinoma (Group II) and 10 negative (Group III) for breast cancer. In order to detect DNA damage, the Comet assay was performed on mammary samples of these animals, which also had samples submitted to the technique of High Performance Liquid Chromatography (HPLC), which aimed to quantify the concentration of pyrethroids. The results of HPLC of each animal were compared with those obtained by the Comet assay analysis of variance and the means were compared by the test groups “Student T” at the significance level of p ￡ 0.05. Despite presenting correlation between the amount of DNA damage and tumor aggressiveness, no statistical differences were found in the DNA damage of different histologic types of breast carcinoma. As for pyrethroids, even these were detected in 22% of tumor tissues and peritumoral fat, there was no difference in DNA damage between cells exposed and not exposed to environmental contaminant.

Role of Nuclear Factor-κB in female Breast Cancer: A Study in Indian Patients

The nuclear factor κB (NF-κB) is a super family of transcription factors which plays important roles in development and progression of cancer. The present investigation concerns NF-κB /p65 activity in human breast cancers with overexpression of ER, PR, HER-2/neu, as well as the significance of p65 expression with regard to menopausal status, stage, grade, tumor size, nodal status, and NPI of invasive ductal carcinomas in Eastern India. In this hospital based study 57 breast cancer patients attending a Breast Clinic of a reputed institute of Eastern India were assessed for p65 protein expression in breast tumor tissue samples by Western blotting. ER, PR and HER-2/neu expression was determined by immunohistochemistry. NF-κB/p65 was significantly associated with advanced stage, large tumor size (≥5 cm), high grade, negative ER, negative PR, and positive HER-2/neu. High NF-κB/p65 expression was more frequent in patients with a high NPI (NPI≥5.4, 84.6%) compared with low NPI (<5.4, 44.4%) and this association was statistically significant (p=0.002). NF-κB/p65 overexpression was associated with advanced stage, large tumor size, high grade, and high NPI which are poor prognostic factors linked to enhanced aggressiveness of the disease. NF-κB/p65 expression implies aggressive biological behavior of breast cancer and this study validates significant association of NF-κB /p65 overexpression with negative estrogen and progesterone receptor status and overexpression of HER-2/neu oncoprotein. In our good clinical practice, patients with NF-κB positive tumors need to be treated aggressively.