Breast Cancer : Basic and Clinical Research最新文献

Background: The association of obesity with breast cancer is clear. Although body mass index (BMI) is used as an indicator of obesity, its accuracy remains questionable. Although, there factors for diagnosing metabolic syndrome are caused by obesity, the association with breast cancer has not been clarified.

Methods: Women who underwent breast cancer screening with mammography and measurements of metabolic syndrome factors, including waist circumference, blood glucose, triglycerides, HDL (high-density lipoprotein) cholesterol levels, and systolic and diastolic pressure, twice within a 2-year period were enrolled (n = 314), with a final sample size of 256. To determine the presence of mammary gland disease, 2 expert physicians interpreted radiogram findings, with category 3 or higher shown by mammography considered to indicate an abnormality.

Results and conclusions: Waist circumference at the initial measurement was marginally significant as a risk factor for onset of mammary gland disease (odds ratio [OR] = 1.036, P = .045) and thus was concluded to be a risk factor for disease onset. Although not significant, a 2-year increase in systolic and diastolic blood pressure has been presumed to be risk factors (systolic: OR = 1.020, P = .085, diastolic: OR = 1.040, P = .065), while high levels of HDL cholesterol have been presumed to protect against the disease (OR = 0.982, P = .064). Based on these results, waist circumference and blood pressure are speculated to be related to development of mammary gland disease.

Background: Early detection of breast cancer is a crucial factor in surviving the disease. This study aimed to investigate the mammography screening based on the theory of planned behavior (TPB) among rural women in Fasa and Shiraz cities, Iran.

Methods: This study is a cross-sectional study performed on 800 female clients referring to rural health centers in Fasa and Shiraz cities in southern Iran in early 2021. The authors decided to send and distribute the electronic questionnaire form through the WhatsApp application in collaboration with the health staff of rural health centers for the people covered by these centers. Data gathering tools were a questionnaire on demographic characteristics, a questionnaire based on constructs of TPB, and behavior of mammography screening. Using the structural equation model (SEM), the TPB constructs and demographic variables were entered into the model. Data analysis was executed employing SPSS software version 26 and Amos version 24 (IBM Co., Ann Arbor, MI, USA). Analyzing the data was carried out using the 1-way analysis of variance (ANOVA), logistic regression, and structural equation analysis. During data analysis, various model indicators such as the goodness of fit, including comparative fit index (CFI), goodness-of-fit index (GFI), root mean square error of approximation (RMSEA), and chi-square index/df were evaluated. The significance level in all tests was considered 0.05.

Results: The knowledge, attitude, and perceived behavioral control were the predictors of intention and behavior of mammography screening among the women. Among demographic variables, age, literacy, being menopausal, cancer in family, city, and ethnicity contribute more to the variance variation in TPB constructs. In this study, 7.2% of Persians, 8% of Qashqai Turks, and 4.5% of Arabs are contemplating going to mammography screening. In total, 6.8% (54 people) of all individuals intended to go mammography screening, and 5.4% (43 people) had a history of mammography screening. Goodness-of-fit indices (χ² = 18.45, df = 10, n = 800, χ²/df = 1.845, RMSEA = 0.032, GFI = 0.90, non-normed fit index (NNFI) = 0.91) of conceptual model of this study indicate the suitability of the model.

Conclusions: The results of the study indicated that the constructs of the TPB can predict mammography screening behaviors in rural women. It has also demonstrated that mammographic behavior can be improved in rural women using education based on the TPB model, emphasizing critical psychological factors of creating or changing behavior.

Purpose: The objective of this study is to determine the impact of exposure to obesity-related systemic factors on fatty acid synthase enzyme (FASN) expression in breast cancer cells.

Methods: MCF-7 breast cancer cells were exposed to sera from patients having obesity or not having obesity and subjected to quantitative reverse transcription polymerase chain reaction (RT-qPCR). Subsequent MTT and colony-forming assays using both MCF-7 and T-47D cells exposed to sera and treated with or without FASN inhibitor, TVB-3166, were used. MCF-7 cells were then treated with insulin and the sterol regulatory element-binding protein (SREBP) processing inhibitor, betulin, prior to analysis of FASN expression by quantitative RT-qPCR and western blot. Insulin-induced SREBP-FASN promoter binding was analyzed by chromatin immunoprecipitation with an anti-SREBP antibody.

Results: In response to sera exposure (body mass index [BMI] >30) there was an increase in FASN expression in breast cancer cells. Furthermore, treatment with the FASN inhibitor, TVB-3166, resulted in a decreased breast cancer cell survival and proliferation while increasing apoptosis upon sera exposure (BMI >30). Insulin-exposed MCF-7 cells exhibited an increased FASN messenger RNA and protein expression, which is abrogated upon SREBP inhibition. In addition, insulin exposure induced enhanced SREBP binding to the FASN promoter.

Conclusions: Our results implicate FASN as a potential mediator of obesity-induced breast cancer aggression and a therapeutic target of patients with obesity-induced breast cancer.

Background: The analysis of disease-free survival and related factors leads to a better understanding of the patient's condition and recurrence-related characteristics and provides a basis for more appropriate treatment guidance. In this study, we aimed to investigate the role of prognostic factors on disease-free survival in breast cancer with a quantile regression model.

Methods: This retrospective study was conducted by reviewing data obtained from 2056 breast cancer patients. Age at diagnosis and education status, tumor size, lymph node ratio, tumor grade, estrogen receptor and progesterone receptor, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were the prognosis factors considered in this study. A quantile regression model was used to investigate prognostic factors of disease-free survival in breast cancer.

Results: Disease recurrence was verified in 251 (13.9%) women, and 39 (0.02%) women died before experience recurrence. The 10th percentile of disease-free survival for patients with the hormone therapy was 23.85 months greater than patients who did not receive this treatment (P value < .001). In the examination of the tumor size, the 10th and 20th percentiles of disease-free survival for patients with tumor size > 5 cm were 31.06 and 27 months less than patients with the tumor size < 2 cm, respectively (P value = .006 and .021, respectively). Compared with grade 1 tumors, the 10th and 20th percentiles of disease-free survival for patients with grade 3 tumors decreased 30.11 and 38.32 months, respectively (P value < .001 and .038, respectively). The 10th and 20th percentiles of disease-free survival decreased 28.16 and 45.32 months with a 1 unit increase in lymph node ratio, respectively (P value = .032 and .032, respectively).

Conclusions: Among the prognostic factors, tumor size, grade, and lymph node ratio showed a close relationship with disease-free survival in breast cancer. The findings indicated that developing public screening and educational programs through the health care system with more emphasis on low-educated women is needed among Iranian women.

Representing 15% to 20% of all invasive breast cancers, adjuvant systemic treatment for early-stage, high-risk triple-negative breast cancer (TNBC) is preferentially done in the neoadjuvant setting based on a chemotherapy backbone of anthracyclines and taxanes. Pathological complete response to neoadjuvant treatment constitutes the main objective, regarding its correlation with oncological outcomes. The optimal neoadjuvant regimen to achieve the highest rates of pathological complete response is still under investigation, with the increasing knowledge on the molecular pathways, genomic sequencing, and immunological profile of TNBC allowing for the development of a wide array of new therapeutic options. This review aims to summarize the current evidence and ongoing clinical trials of new therapeutic options for the neoadjuvant treatment of TNBC patients.

Introduction: The ability to accurately predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer would improve patient selection for specific treatment strategies, would provide important information for patients to aid in the treatment selection process, and could potentially avoid the need for more extensive surgery. The diagnostic performance of magnetic resonance imaging (MRI) in predicting pCR has previously been studied, with mixed results. Magnetic resonance imaging performance may also be influenced by tumour and patient factors.

Methods: Eighty-seven breast cancer patients who underwent NAC were studied. Pre-NAC and post-NAC MRI findings were compared with pathologic findings postsurgical excision. The impact of patient and tumour characteristics on MRI accuracy was evaluated.

Results: The mean (SD) age of participants was 48.7 (10.3) years. The rate of pCR based on post-NAC MRI was 19.5% overall (19/87). The sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy in predicting pCR were 52.9%, 77.1%, 36.0%, 87.1%, and 72.4%, respectively. Positive predictive value was the highest in nonluminal versus Luminal A disease (45.0% vs 25.0%, P < .001), with higher rates of false positivity in nonluminal subtypes (P = .002). Tumour grade, T category, and histological subtype were all independent predictors of MRI accuracy regarding post-NAC tumour size.

Conclusion: Magnetic resonance imaging alone is insufficient to accurately predict pCR in breast cancer patients post-NAC. Magnetic resonance imaging predictions of pCR are more accurate in nonluminal subtypes. Tumour grade, T category, and histological subtype should be considered when evaluating post-NAC tumour sizes.

Introduction: Karanahan, a cancer treatment technology aimed at eradicating tumor-initiating stem cells, has already proven effective in 7 tumor models. Karanahan comprises the following procedures: (1) collecting surgical specimens, (2) determining the duration of the DNA repair process in tumor cells exposed to a cross-linking cytostatic agent, and (3) determining the time point, when cells, including tumor-initiating stem cells, are synchronized in the certain phase of the cell cycle after triple exposure to the cytostatic, becoming vulnerable for the terminal treatment, which is supposed to completely eliminate the rest of survived tumor-initiating stem cells. Determining these basic tumor properties allows to design the schedule for the administration of a cross-linking cytostatic and a complex composite DNA preparation. Being conducted in accordance with the schedule designed, Karanahan results in the large-scale apoptosis of tumor cells with elimination of tumor-initiating stem cells.

Methods: Breast tumor specimens were obtained from patients, and basic tumor properties essential for conducting Karanahan therapy were determined.

Results: We report the first use of Karanahan in patients diagnosed with breast cancer. Technical details of handling surgical specimens for determining the essential Karanahan parameters (tumor volume, cell number, cell proliferation status, etc) have been worked out. The terminally ill patient, who was undergoing palliative treatment and whose tumor specimen matched the required criteria, received a complete course of Karanahan.

Conclusions: The results of the treatment conducted indicate that Karanahan technology has a therapeutic potency and can be used as a breast cancer treatment option.

Background: Resistance to endocrine therapy has been a major obstacle in the management of hormone receptor (HR)-positive metastatic breast cancer (MBC). Meanwhile, a number of treatments are available to such patients, and physicians often encounter difficulties in choosing the most appropriate treatments for individual patients. The combination of CDK 4/6 inhibitors (CDKi) and endocrine therapy has now become a standard treatment for HR-positive and human epidermal growth factor receptor 2 (HER2)-negative MBC. However, no predictive markers for CDKi-based treatments have been established. Considering their side effects and the financial burden on patients, identifying such markers is crucial.

Methods: Clinicopathological features of 107 patients with HR-positive HER2-negative MBC, who received CDKi-based treatments at our institution were retrospectively investigated. HR status in distant metastatic lesions and immunocompetent cells in peripheral blood were also studied.

Results: Progression-free survival (PFS) was significantly shorter in patients whose primary tumour was high grade (P = 0.016) or high neutrophil-to-lymphocyte ratio (NLR) at baseline (P = 0.017). Meanwhile, there were no differences in other factors, such as expression levels of hormone receptors. Patients whose metastatic lesions were of low tumour grade or high Ki67 labelling index had longer PFS, and such trends were more obvious than primary lesions.

Conclusion: Our data indicate that tumour grade in primary lesion and NLR are potential predictive factors for CDKi-based treatments. Moreover, pathological assessment of metastatic lesions might also be useful.