Search

As one of the frequent malignancies, breast cancer (BCa) is the foremost reason for cancer-related deaths among women. The role of Human papillomavirus (HPV) in chemoresistance has rarely been investigated in previous studies. The current study sets out to the possible role of HPV in BCa chemoresistance. In this research, 90 BCa tissue and 33 normal breast tissue were collected. We evaluated the presence of the HPV genome along with the viral (E2, E6, E7) and cellular gene expression associated with cell resistance to death. Statically significant differences in the prevalence of HPV between the BCa group (25.2% or 23/90) and the control group (21.8% or 7/32) were not found. HPV-16 and HPV-18 genotypes were the abundant HPV genotypes. Resistance to the Adriamycin-Cyclophosphamide (AC), paclitaxel regimen was elevated in the HPV- group (56/70) in comparison to the HPV+ group (14/70). Nevertheless, there was no significant difference in the prevalence of resistance to AC + paclitaxel + triple-negative breast cancer combination therapy between the HPV+ group (9/20) and in the HPV- group (11/20). In the BCa group in contrast to the control group, the expression level of Bcl-2, BCL-XL, and c-IAP2 demonstrated a significant decrease, while, the expression level of cytochrome C and caspase 3 was significantly increased. This study suggests that HPV infection might contribute to BCa chemoresistance through disrupt cellular genes involved in cell death., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

In this research, DNA-modified carbon dots (CDs) were exploited to construct a fluorescence assay for breast cancer genes (BRCA1, a potential marker for cancer diagnosis) detection. For this purpose, water-soluble synthesized CDs were functionalized with 19 mer-modified oligonucleotides (capture probe). By adding the DNA target, the specific binding between the DNA probe and DNA target causes fluorescence quenching. The assay displayed a fine capability of sensing the BRCA1 gene with a linear range (R 2  = 0.9918) of 36 attomolar (aM) to 532 femtomolar (fM) and a detection limit of 2 attomolar. This homogeneous process does not need additional separation and washing steps of un-hybridized DNA. To assess the selectivity, the prepared biosensor responses were evaluated in solutions containing single-base mismatched DNA sequences, three-base mismatched DNA sequences, or non-complementary DNA sequences, separately. To demonstrate the practical application of the designed biosensor, the extracted DNA from blood samples of breast cancer patients was utilized as real samples. When the CDs-DNA bioassay was exploited in the imaging of MCF-7 cancer cells, strong fluorescence emission was observed. After incubation times, both the cells' size and shape remained unchanged. The results validated that the CDs are an extremely great bioimaging candidate in disease diagnosis, biomedicine investigation, and managing cancer diseases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2-positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran., Methods: Patients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity., Results: Ninety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (- 0·03 [95% CI - 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively. At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups., Conclusions: Non-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups., (© 2022. The Author(s).)

Background: Breast cancer is currently the most common neoplasm diagnosed in women globally. There is a growing body of evidence to suggest that human papillomavirus (HPV) infection may play a key role in invasiveness of breast cancer. The aim of this study was to determine the presence of HPV in patients with breast cancer and its possible association with cancer progression., Methods: Breast specimens were collected from 72 patients with breast cancer and 31 healthy controls. The presence of HPV was investigated by polymerase chain reaction (PCR) and genotyping was performed for positive cases. We also evaluated the viral factors such as E6, E2, and E7 in HPV positive cases. Enzyme-linked immunosorbent assay (ELISA (and Real-time PCR techniques were used to measure the expression level of anti-carcinogenic genes, such as p53, retinoblastoma (RB), breast and ovarian cancer susceptibility gene (BRCA1, BRCA2) and inflammatory cytokines, including tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β), nuclear factor-kB (NF-kB), and different interleukins [ILs] (IL-1,IL6, and IL-17)., Results: The HPV DNA was detected in 48.6% of breast cancer samples, whereas only 16.1% of controls were positive for HPV. We observed statistically significant differences between breast cancer patients and HPV presence (P = 0.003). HPV type 18 was the most prevalent virus genotype in patients. The expression of P53, RB, BRCA1, and BRCA2 were decreased in patients with HPV-positive breast cancer as compared to HPV-negative breast cancer and healthy controls. (All P-values were less than 0.05). The presence of the HPV was associated with increased inflammatory cytokines (IL-1, IL-6, IL-17, TGF-β, TNF-α, and NF-kB) and tumor progression., Conclusion: The present study demonstrated that HPV infection may implicate in the development of some types of breast cancer.

Breast cancer is the most common cancer with high morbidity and mortality among women worldwide. Aberrant hypermethylation in promoter regions of the tumor suppressor genes such as PTEN gene is a key event in the progression and development of breast cancer. The aim of the present study was to evaluate an association between PTEN gene methylation status with the risk of breast cancer in an Iranian population. We studied 255 individuals, including 103 patients with breast cancer, 102 first-degree female relatives of patients (mother, sister, or daughter of patients), and 50 healthy individuals as a control group. Genomic DNA was extracted from peripheral blood leukocytes, and the PTEN promoter methylation status was detected using methylation-specific PCR (MSP) method with specific methylated and unmethylated primers. In some samples, direct DNA sequencing was used to confirm the results obtained by the MSP method. The frequency of PTEN-methylated (MM) genotype was 6 % in the healthy control group, 23.3 % in relatives of patients, and 41.7 % in patients (χ (2) = 24.62, p < 0.001). There were significant differences in the frequency of PTEN-methylated genotype between healthy control compared to that in patients (χ (2) = 15.1, p < 0.001) and also compared to that in relatives of patients (χ (2) = 6.9, p = 0.009). In the presence of PTEN MM genotype, there was a 3.1-fold susceptibility to breast cancer compared to the UU genotype (p < 0.001). Also, in the presence of PTEN M allele, the risk of breast cancer was 2.71-fold compared to the presence of U allele (p < 0.001). Our findings indicated increased frequency of hypermethylation of PTEN promoter in the studied patients and their relatives that could be considered as one of the epigenetic factors affecting the risk of breast cancer in Iranians.

Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases., Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as ≥10% positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3+ by IHC. For HER2 (2+), FISH was performed to determine HER2 positivity., Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor size<2cm and also Ki-67≥20% as compared to the HER2-positive group., Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index ≥20% in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-67≥20% had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.

Background: Breast cancer is a very common health problem in Iranian women. The HER2-neu gene is a transmembrane receptor tyrosine kinase with homology to members of the EGF receptor family. The aim of this study was to investigate the association between HER2-neu oncogene status with prognostic factors of breast cancer in Kermanshah province, Iran., Materials and Methods: Relationship between HER2-neu and prognostic factors of 130 cases of breast cancer were evaluated during two years in Imam Reza hospital in Kermanshah, Iran. Data were analyzed using descriptive statistics and the T-test and Mann-Whitney U non-parametric test using SPSS 19., Results: The mean age for the patients was 46.0±8.0 years, all being female. Among the predictive factors for breast cancer were family history, stage of disease, involvement of the lymphovascular system, number of involved lymph nodes in axillaries, grading and hormone receptor status with HER2-neu oncogene had direct correlation and between factors, tumor location, patient age and histological characteristics and HER2-neu oncogene had no significant relationship. We found significant correlation between HER2 with ER and PR and also HER2 with ER, PR negative., Conclusions: HER2-neu is risk factor that can be a good prognostic and also predictive factor. For these reasons, we recommend that it be evaluated for all types of BC.

Background: In breast cancer (BC), it has been suggested that nuclear overexpression of p53 protein might be an indicator of poor prognosis. The aim of the current study was to evaluate the expression of p53 BC in Kurdish women from the West of Iran and its correlation with other clinicopathology figures., Materials and Methods: In the present retrospective study, 231 patients were investigated for estrogen receptor (ER) and progesterone receptor (PR) positivity, defined as ≥10% positive tumor cells with nuclear staining. A binary logistic regression model was selected using Akaike Information Criteria (AIC) in stepwise selection for determination of important factors., Results: ER, PR, the human epidermal growth factor receptor 2 (HER2) and p53 were positive in 58.4%, 55.4%, 59.7% and 45% of cases, respectively. Ki67 index was divided into two groups: 54.5% had Ki67<20% and 45.5% had Ki67 ≥20%. Of 214 patients, 137(64%) had lymph node metastasis and of 186 patients, 122(65.6%) had vascular invasion. Binary logistic regression analysis showed that there was inverse significant correlation between lymph node metastasis (P=0.008, OR 0.120 and 95%CI 0.025-0.574), ER status (P=0.006, OR 0.080, 95%CI 0.014-0.477) and a direct correlation between HER2 (P=005, OR 3.047, 95%CI 1.407-6.599) with the expression of p53., Conclusions: As in a number of studies, expression of p53 had a inverse correlation with lymph node metastasis and ER status and also a direct correlation with HER2 status. Also, p53-positivity is more likely in triple negative BC compared to other subtypes.

Background: Breast cancer (BC) is the most frequent malignancy among females and is a leading cause of death of middle-aged women. Herein, we evaluated baseline characteristics for BC patients and also compared these variables across ealry and late recurrence groups., Materials and Methods: Between 1995 to 2014, among female breast cancer patients referred to our oncology clinic, eighty-six were entered into our study. All had distant metastasis. Early recurrence was defined as initial recurrence within 5 years following curative surgery irrespective of site. Likewise, late recurrence was defined as initial recurrence after 5 years. No recurrence was defined for survivors to a complete minimum of 10 years follow-up. Significant prognostic factors associated with early or late recurrence were selected according to the Akaike Information Criterion., Results: The median follow-up was 9 years (range, 1-18 years). During follow-up period, 51 recurrences occurred (distant metastasis), 31 early and 20 late. According to the site of recurrence, there were 51 distant. In this follow-up period, 19 patients died. Compared with the early recurrence group, the no recurrence group had lower lymph node involvement and more p53 positive lesions but the late recurrence group had lower tumor size. In comparison to no recurrence, p53 (odds ratio [OR] 6.94, 95% CI 1.49-32.16) was a significant prognostic factor for early recurrence within 5 years., Conclusions: Tumor size, p53 and LN metastasis are the most important risk factors for distance recurrence especially in early recurrence and also between of them, p53 is significant prognostic factor for early recurrence.

Background: The Functional Assessment of Cancer Therapy - Breast (FACT-B) scale is widely used to measure health-related quality of life in cancer patients. The aim of the present study is to validate the FACT-B in a sample of Iranian women with breast cancer., Materials and Methods: The sample consisted of 300 women selected through non-random convenient sampling procedure from oncology hospitals and clinics in Kermanshah and Shiraz cities. They were asked to fill in the Persian versions of the FACT-B scale, Hospital Anxiety and Depression Scale, the European Organization for Research and Treatment of Cancer quality of life EORTC QLQ30. Confirmatory factorial analysis of the methods, concurrent validity and discriminant, and Cronbach's alpha for internal consistency were applied., Results: Internal consistency using Cronbach's alpha was 0.63 to 0.93 for the subscales and 0.92 for the total scale. Significant correlations between FACT- B and other measures indicate that this scale had concurrent and discriminant validity. The values of fit indices were satisfactory., Conclusions: The Persian version of the FACT-B scale is valid and reliable and, therefore, the scale can be used in research and clinical settings to assess health-related quality of life in Iranian patients with breast cancer.