Breast Cancer : Basic and Clinical Research最新文献

Background: Breast cancer is the most common cancer in women, and the second overall, following lung cancer. Breast cancer can occur at any age, with an increased incidence in women 40 years and above. Worldwide the incidence is around 1 million cases per year, 60% of the cases reported from low- and middle-income countries. The current study was conducted to determine knowledge, attitude, and practices related to breast cancer, the associated risk factors, and screening methods in women presenting to a health care facility from resource-poor settings in Pakistan.

Methods: A cross-sectional study design was used, and participants were recruited phase-wise from three major outpatient departments (OPDs) (Gynecology and Obstetrics OPD, Medical OPD, and Surgical OPD). Data were collected through the validated "Breast Cancer Awareness Measure" developed by Cancer Research UK, King's College London, and University College London in 2009. Data were analyzed through Statistical Package for Social Sciences software (SPSS) version 23.0. Students's T-Test, ANOVA, and linear regression analysis were conducted.

Results: A total of 430 women were invited for participation in the study from the 3 main OPDs, and 400 took part in the study (response rate = 93.02%). The mean age of the women was 33.62 years ± 12.3 years, and the mean years of formal education were 5.05 ± 6.3 years. Less than a quarter of the participants were aware of the breast cancer warning signs, and 23.3% recognized the pain in the armpit or one of the breasts as a sign of breast cancer. The proportion of women aware of age-related and lifetime risk of getting breast cancer was 15.0%. Furthermore, only 2.5% performed breast self-examination at least once a month. Women identified many barriers like embarrassment, transport, and confidentiality issues in seeking medical help.

Conclusion: Overall, women had poor knowledge of breast cancer, related warning signs, breast self-examination, risk factors, and screening methods.

Background: Sentinel lymph node biopsy (SLNB) provides staging information and guides adjuvant therapy in early breast cancer (EBC). Routine SLNB in oncogeriatricians with low-risk EBC remains controversial.

Aims: To evaluate axillary management in elderly patients diagnosed with oestrogen receptor positive (ER+), clinically lymph node negative (cLN-) EBC, and to assess whether SLNB affects further axillary management or adjuvant chemotherapy (ACTX) decision making.

Methods: Female patients aged > 65 years, diagnosed with ER+, human epidermal growth factor receptor-2 negative (HER2-), and cLN- breast cancer (BC), who underwent surgery and SLNB were included. Clinicopathological predictors of ACTX and completion axillary lymph node dissection (CALND) were determined. Kaplan-Meier analyses assessed survival outcomes.

Results: A total of 253 patients were included (median age: 72 years, range: 66-90), all underwent SLNB; 50 (19.8%) had lymphatic metastasis on SLNB (SLNB+). Of these, 19 proceeded to CALND (38.0%), 10 (52.6%) of whom had further axillary disease (ALND+). 20 of the 50 SLNB+ patients received ACTX (40.0%) as did 31 of the 203 SLNB- patients (15.2%) (P < .001). Oncotype DX (ODX) testing was utilized in 82 cases (32.8%). Younger age (P < .001), SLNB+ (P < .001) and ODX score (P = .003) were all associated with ACTX prescription. ODX > 25 (OR: 4.37, 95% CI: 1.38-13.80, P = .012) independently predicted receiving ACTX. Receiving ACTX and proceeding to CALND did not improve disease-free (P = .485 and P = .345) or overall survival (P = .981 and P = .646).

Conclusions: Routine SNLB may not be necessary in elderly patients diagnosed with ER+, cLN- EBC. Future oncogeriatric practice is likely to see genomic testing guiding ACTX prescription in this group.

Purpose: Triple-negative breast cancer (TNBC) is a subset of breast cancer which is known to carry a poor prognosis because of lack of targets for hormonal therapy. Research efforts have focused in recent years on discovering biomarkers of management in TNBCs. KI-67 Labelling Index (LI) is a nuclear protein which has proven to play diagnostic and prognostic roles in many cancers.

Materials and methods: We analysed the expression of KI-67 LI by immunohistochemistry in TNBC cases from the University hospital. This expression was cross-checked against clinical-pathological criteria of TNBC patients and against Vimentin expression in TNBC patients with significant KI-67 expression.

Results: KI-67 LI was significantly expressed in the majority of TNBC cases. This expression was significantly correlated with lymph node metastases, tumour invasion, high tumour nuclear grade, clinical stage, adverse survival outcome, and failure to achieve pathological complete response. TNBCs' KI-67 LI expression was also correlated with Vimentin expression, the mesenchymal chief marker of the EMT phenomenon.

Conclusion: Collectively, our study presents a strong argument for the use of KI-67 LI as a biomarker of aggressive, metastatic TNBC disease with poor outcome. This study, along with mounting evidence in the scientific literature, presents a case for the use of this nuclear protein in diagnosis, prognosis, and follow-up of patients with this difficult diagnosis.

Background: Breast cancer is the most common cancer in women, and its incidence and mortality rates are expected to increase significantly over the next few years, particularly in developing countries. The aim of this study was to describe the epidemiological, clinical, radiological, histopathological, and prognostic aspects of breast cancer in Togo.

Materials and methods: We retrospectively analyzed at our Department of Pathology of Lomé all cases of breast cancer in women confirmed by histology over a period of 20 years (2000-2019).

Results: We collected 804 cases of breast cancer in women. The median age was 46.7 years (range, 12-86 years). Patients aged <40 years represented 48.38% of cases, and the left breast was more affected (51.24%). Most women were sexually active (71.52%) and resided in urban areas (66.29%). Carcinomas represented the predominant histological group (796 cases, 99.00%) with a predominance of invasive nonspecific type carcinoma (92.34%). These cancers were diagnosed at late stage III using Nottingham grading (55.10%). The TNM classification showed a predominance of grades T2NxMx (72.45%) and T4N1Mx (17.76%). The luminal B profile (40.85%) was found mostly, and the mutation of BRCA2 and BRCA1 genes was found in 2.61% of cases. Mastectomy was performed in 7.59%, radiotherapy in 3.61%, and chemotherapy in 18.66%.

Conclusion: Breast cancer is a frequent pathology in Togolese women, predominant in young adults, often diagnosed at a late stage with limited possibilities of treatment. The establishment of early care programs is essential.

Purpose: Clinical studies have shown that breast cancer risk is increased in hypertensive women. The underlying molecular mechanism remains undetermined. The current study tests our hypothesis that G protein coupled receptor kinase 4 (GRK4) is a molecule that links hypertension and breast cancer. GRK4 plays an important role in regulation of renal sodium excretion. Sustained activation of GRK4 as in the circumstances of single nucleotide polymorphism (SNPs) causes hypertension. Expression of GRK4 in the kidney is regulated by cMyc, an oncogene that is amplified in breast cancer.

Methods: Western analysis was used to evaluate GRK4 protein expression in seven breast cancer cell lines. GRK4 gene single nucleotide polymorphism in breast cancer cell lines and in breast cancer cDNA arrays were determined using TaqMan Genotyping qPRC. The function of GRK4 was evaluated in MCF-7 cells with cMyc knock-down and GRK4 re-expression and in MDA-MB-468 cells expressing inducible GRK4 shRNA lentivirus constructs. Nuclei counting and 5-Bromo-2'-deoxy-uridine (BrdU) labeling were used to evaluate cell growth and proliferation.

Results: Genotyping of GRK4 SNPs in breast cancer cDNA arrays (n = 94) revealed that the frequency of carrying two hypertension related SNPs A142 V or R65 L is threefold higher in breast cancer patients than in healthy people (P = 7.53E-11). GRK4 protein is expressed in seven breast cancer cell lines but not the benign mammary epithelial cell line, MCF-10A. Three hypertension related SNPs in the GRK4 gene were identified in the breast cancer cell lines. Except for BT20, all other breast cancer lines have 1-3 GRK4 SNPs of which A142 V occurs in all 6 lines. MDA-MB-468 cells contain homozygous A142 V and R65 L SNPs. Knocking down cMyc in MCF-7 cells significantly reduced the growth rate, which was rescued by re-expression of GRK4. We then generated three stable GRK4 knock-down MDA-MB-468 lines using inducible lentiviral shRNA vectors. Doxycycline (Dox) induced GRK4 silencing significantly reduced GRK4 mRNA and protein levels, growth rates, and proliferation. As a marker of cell proliferation, the percentage of BrdU-labeled cells decreased from 45 ± 3% in the cells without Dox to 32 ± 5% in the cells treated with 0.1 µg/mL Dox.

Conclusions: GRK4 acts as an independent proliferation promotor in breast cancer. Our results suggest that targeted inhibition of GRK4 could be a new therapy for both hypertension and breast cancer.

Introduction: Almost 50% to 70% of patients who undergo axillary lymph node dissection (ALND) because of a single metastatic sentinel lymph node (SLN) have no further metastatic nodes at the axillary histology. On these grounds, the one-step nucleic acid amplification (OSNA) nomogram was designed and validated. As a mathematical model, calculated through tumor size (expressed in millimeters) and CK19 mRNA copy number, it is thought to predict nonsentinel lymph node (NSLN) status. The aim of the study is to verify the diagnostic accuracy of the OSNA nomogram in a group of patients with macrometastatic SLN, with a retrospective analysis.

Methods: The OSNA nomogram was retrospectively applied to a group of 66 patients with macrometastatic SLN who underwent ALND. The result of the final histology of the axillary cavity was compared to the nomogram prediction. We calculated the prevalence of NSLN metastasis in patients who underwent ALND, sensitivity and specificity, negative and positive predictive value of the nomogram.

Results: In patients with macrometastasis in SLN, the prevalence of patients with metastatic NSLN was 45%. The sensitivity of the nomogram was excellent (90%). The specificity was low (36%). Positive predictive value amounted to 54%, while negative predictive value was good (81%).

Conclusions: These results suggest that the OSNA nomogram is a valid instrument that can help choose the best surgical strategy for the treatment of axillary cavity. The mathematical model is useful to avoid surgery in a selected group of patients because it accurately predicts NSLN status.

Purpose: It has been suggested that Shiga-like toxins produced by Escherichia coli O157:H7 could be used as novel therapeutic agents against malignant tumors. In addition, the antitumor potency of local isolates from Indonesia, which are known to be less toxic than the control isolate ATCC 43894, has not yet been tested. The study aimed to analyze local strains of E. coli O157:H7 as a proapoptosis agent on the T47 breast cancer cell line.

Methods: As many as 30 culture cells of T47D breast cancer cell line were subjected to purified extracts of Shiga-like toxin originating from 5 local isolates of E. coli O157:H7: KL-48(2), SM-25(1), SM-7(1), DS-21(4), and 1 isolate ATCC 43894 which was used as a control. Toxin production of each isolate was detected using a sandwich enzyme-linked immunosorbent assay, and the treatment of cell lines was observed for 24 hours, with 2 replications; 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide tests and acridine orange/ethidium bromide double staining assays were used for detection and analyses of apoptosis.

Results: The study showed 2 local strains of E. coli O157:H7 (codes KL-48(2) and SM-25(1)) had toxins positive at titer 5 and 10 μg/100 μL. These titers were lower than the control isolate ATCC 43894, but they had a necrosis effect higher (P < .05), ie, 80.3%, than control isolate, ie, 63.3%. Other local strain SM-25(1) also had a good necrosis effect. It has a nondifferent necrosis effect (P > .05) with the control isolate ATCC 43894, ie, 13.0% from 13.3%.

Conclusion: This study concludes that the Shiga toxin produced by E. coli O157:H7 local isolate (Indonesia) has potential as a proapoptotic and/or necrotic agent for treating T47 breast cancer cell lines, as effectively as ATCC 43894 control isolates.

Introduction: In Uruguay, breast cancer has the highest incidence and mortality of all cancer in women. Knowledge of the distribution of risk factors related to disease development supports the implementation of prevention strategies in routine clinical practice. This study aimed to determine the epidemiological profile for breast cancer and the frequency of mammographic surveillance in the surveyed population.

Materials and methods: A survey was conducted among Uruguayan women diagnosed with breast cancer who were assisted in the mastology unit of the oncology service of the Hospital de Clínicas in Montevideo, Uruguay, from September 1, 2018, to March 1, 2020.

Results: This study included 398 respondents, with a median (SD) age at diagnosis of 61 (34-86) years. A total of 310 respondents (78.0%) had 1 or more risk factors. Most women aged over 50 years (264 out of a total of 338 [78.1%]) underwent mammographic surveillance at least biennially.

Conclusions: Consistent with international reports, most respondents had a risk factor. Among the group of respondents aged over 50 years, most underwent mammographic and clinical surveillance at least biennially. Although it is only possible to formulate conclusions about the surveyed women because of the study design, the obtained data further our understanding of the epidemiological profile of the Uruguayan population, which can contribute to prevention practices.

Tumour lysis syndrome (TLS) is a medical emergency occurring when large numbers of cancer cells rapidly undergo cell death. The resultant metabolic abnormalities results in significant morbidity and mortality. Tumour lysis syndrome most commonly occurs in 5% of haematological malignancies and is less commonly described in solid organ cancers. In breast cancer, TLS has been reported to occur both spontaneously and as a result of cancer chemotherapy, targeted therapy, or radiotherapy. However, only 1 TLS case in a breast cancer patient has been reported as a consequence of aromatase inhibitor letrozole. With the increased recent use of CDK4/6 inhibitors, 2 cases of hyperuricaemia in patients with breast cancer treated with palbociclib/letrozole combination treatment have also been reported. We present the second case of letrozole-induced TLS in a 74-year-old woman with occult breast adenocarcinoma. Despite treatment with recombinant urate oxidase and intravenous fluids, the patient deteriorated and was discharged with hospice care. Although rare, this life-threatening condition should be considered in an acutely unwell patient commencing treatment for solid malignant tumours.

Background: Male breast carcinoma (male BC) is an uncommon neoplasia without individualized strategies for diagnosis and therapeutics. Low overall survival (OS) rates have been reported, mostly associated with patients' advanced stage and older age. Intratumoral heterogeneity versus homogeneity of malignant epithelial cells seems to be an important factor to consider for the development of combination therapies with curative intention.

Objective: In this preliminary study, we aim to provide valuable insight into the distinct clinicopathologic features of male BC.

Material and methods: In a series of 40 male BC patients, we evaluated by immunohistochemistry androgen receptor; activating transcription factor 3 (ATF3); p16; cyclin D1; fatty acid synthase (FASN); fatty acid transport protein 1 (FATP1); β1, β3, β4, and β6 integrins; collagen I and collagen IV; and their interactions. Kaplan-Meier survival curves and log-rank tests were assessed for statistical analysis.

Results: Homogeneous epithelial staining of p16, ATF3, β6 integrin, FASN, and FATP1 was found to be significantly intercorrelated, and associated with high Ki67. These markers also stained tumor stromal fibroblasts. The prognostic analysis showed statistically significant associations of FASN with disease-free survival (DFS) and OS, as well as of ATF3 with OS and collagen IV with DFS.

Conclusions: This study highlights, as a novel finding, the relevance of FASN, ATF3, and collagen IV immunophenotypes, which may have innovative application in the clinical management of male BC.