Breast Cancer : Basic and Clinical Research最新文献

Background: The management of early breast cancer patients with metastatic sentinel lymph nodes (SLNs) remains a critical decision point in balancing survival outcomes with surgical morbidities. This study addresses whether sentinel lymph node biopsy (SLNB) with or without regional node irradiation (RNI) can offer comparable survival outcomes to axillary lymph node dissection (ALND).

Objectives: To evaluate overall survival (OS), disease-free survival (DFS), locoregional recurrence (LRR), and mortality outcomes of SLNB (with or without RNI) compared with ALND in patients with metastasis-positive SLNs.

Design: We have performed an updated meta-analysis of randomized controlled trials (RCTs) comparing SLNB alone or with RNI vs. ALND for early breast cancer patients with metastatic SLNs.

Data sources and methods: Eligibility criteria included RCTs comparing SLNB ± RNI vs ALND for metastasis-positive SLN. PubMed, EMBASE, the Cochrane library, and online registers were searched for articles comparing SLNB alone vs. ALND for metastasis-positive SLN. Articles were evaluated for risk of bias using Cochrane's revised tool (RoB). The main summary measures using the random effects model were hazard ratio and risk ratio.

Results: Seven RCTs were included in the meta-analysis. Overall survival and DFS were superior in the SLNB group compared to the ALND group. Locoregional recurrence and mortality were comparable between both the groups. After stratifying RCTs with regards to adjuvant RNI, these parameters were still comparable to ALND.

Conclusion: This meta-analysis suggests that SLNB, with or without RNI, offers comparable OS and DFS to ALND for early breast cancer patients with metastasis-positive SLNs. However, the inclusion of studies that did not differentiate between micrometastases and macrometastases may introduce bias, particularly when assessing the impact of RNI. The role of RNI remains debated specially in those with macrometastases, and future research should focus on stratified analyses to clarify this. While SLNB represents a viable alternative to ALND, further trials are needed to define the optimal role in subgroups with high-risk tumor biology.

Background: Breast phyllodes tumor (PT) is a biphasic tumor and constitutes about 0.3% to 1% of all breast tumors. The PT is histologically classified as benign, borderline, and malignant subtypes. Unlike epithelial breast cancers, PT is derived from breast fibroepithelial tissues, and the genomic information of PT subtypes is still limited.

Objectives: The objectives were to gain a deeper understanding of genomic changes in the progression of PTs from benign and borderline to malignant.

Design: In this study, we used an Affymetrix OncoScan Array to analyze the genome-wide copy number variations (CNVs) and nucleotide point mutations from 3 benign PTs, 3 borderline PTs, and 3 malignant PTs collected from the First Affiliated Hospital of Zhengzhou University.

Methods: DNA was extracted from formalin-fixed paraffin-embedded (FFPE) specimens using the TIANamp FFPE DNA Kit. The DNA was profiled for genome-wide CNV using the Affymetrix OncoScan Array and analyzed using the Nexus Express Chromosome Analysis Suite.

Results: Our in silico variation analysis indicated copy number loss in Xp11.22 to q22.1 of all benign PTs (χ² = 9, P = .0027) and 22q11.23 and Xq23 in all malignant PTs (χ² = 12, P = .0005). A copy number gain was observed in 1p13.3 of all borderline PTs (χ² = 9, P = .0027) and 7p11.2 of all malignant PTs (χ² = 9, P = .0027). We also found consistent loss of heterozygosity (LOH) in 32 loci of benign PTs, 32 loci of borderline PTs, and 23 loci of malignant PTs. Among the 87 LOH, there were 15 overlapping loci across all PT subtypes. We observed missense mutations of NRAS, KRAS, IDH2, TP53, and a frameshift deletion in PTEN of sequenced PT samples, irrespective of their subtype. Interestingly, a point mutation in EGFR/EGFR-AS1 was only observed in malignant PTs.

Conclusions: Our data suggested that CNV at 7p11.2, 22q11.23, and Xq23 together with a point mutation in EGFR/EGFR-AS1 uniquely presented in malignant PTs may correlate with the progression of PTs.

Background: Depression commonly occurs in patients with breast cancer (BC), affecting their quality of life.

Objectives: The relationships between depression and different sociodemographic characteristics in patients with BC are under-researched. We conducted a multicenter study to determine the magnitude of depression and its association with different sociodemographic characteristics.

Design: In this multi-institutional study, clinical data were collected, prospectively between October 2019 and January 2023 from 207 patients who were on active treatment for BC diagnosis in tertiary oncology hospitals in Georgia.

Methods: Patients' sociodemographic characteristics were analyzed and their association with depression was assessed, using Patient Health Questionnaire-9 (PHQ-9) for the identification of depressive symptoms. Patients were stratified using basic information.

Results: The median age of participants was 53 years (ranging from 31 to 77). Of the participants, 63.2% were married, 44.5% were employed, and only 16.4% reported having adequate financial status. Based on pro-rated PHQ-9 scores, 42% of patients reported some level of depressive symptoms, and 14.5% met the criteria for probable depressive disorder. Women with very inadequate financial status (10/21, 47.6%) reported significantly more depressive symptoms than those with adequate financial support (3/34, 8.8%) (P = .001). Unemployed women (12/42, 28.6%) were nearly 3 times more likely to experience moderate or severe depressive symptoms compared with employed patients (8/92, 8.7%) (P = .002). A significant difference in depressive symptoms was also observed based on education level, with individuals with higher education (12/119, 10%) reporting fewer depressive symptoms compared with those with middle education (18/88, 20.4%) (P = .036). No statistically significant difference in depressive symptoms was found based on marital status or social support.

Conclusions: Our study found a significant relationship between depression and factors such as financial status, education level, and employment. Lower household income and education level were identified as predictors of clinical depression among patients with BC. These findings can help oncologists in Georgia recognize the importance of providing psychological support to cancer patients. Early detection and prompt referral to mental health specialists can play a key role in effectively managing depression.

Background: The surgical management of breast cancer involves either modified radical mastectomy or a conservative approach. Breast-conserving surgery is the preferred surgical treatment for early breast cancer in developed countries, while mastectomy is still more favoured by most centres in developing countries.

Objectives: To report some quality data on breast cancer surgeries from a sub-urban tertiary hospital in Nigeria.

Design: Retrospective analysis.

Methods: We retrospectively reviewed all breast cancer surgeries performed between January 2018 and December 2022 at the Irrua Specialist Teaching Hospital.

Results: A total of 105 female patients underwent breast cancer surgery. Their ages ranged between 27 and 85 years, with a mean of 48.8 years (SD = 12.2). The mean duration of symptoms before presentation was 12.3 ± 17.8 months (1-120 months), with 15.2% presenting with stage I and II disease and 84.7% presenting with stage III and IV disease. Invasive carcinoma NST was the most common histological type in 78 (74.3%) patients. The cancers were predominantly high grade (42.3%) and triple negative (41.5%). Only 9.5% of the patients had breast-conserving surgery, the others had mastectomy. Sixty-three patients (60%) received neoadjuvant chemotherapy while only 25.7% of patients had documented evidence of the completion of adjuvant radiotherapy.

Conclusion: The rate of breast-conserving surgery in this study was extremely low. This could be attributed to the advanced stage at presentation, predominance of aggressive tumours, limited access to radiation therapy, status of the medical system, and patient preferences.

Background: Breast cancer is the most common malignancy in women and the leading cause of cancer-related death. Although most early-stage patients are cured, 20% to 30% develop metastases, significantly reducing survival rates. Recent research highlights the role of iron in cancer progression, although its full impact on breast cancer metastasis is not yet fully understood.

Objectives: The aim of this study is to investigate the association between plasma iron levels at diagnosis of early-stage breast cancer and the risk of developing metastatic disease.

Design: Retrospective single-center study.

Methods: Patients with stage I to III breast cancer, diagnosed between 2007 and 2017, and with serum iron, transferrin saturation, and ferritin values available within 1.5 months before or after diagnosis were included. Cox proportional hazard models were applied to determine the association between iron levels and risk of metastasis.

Results: In total, 1113 patients were included, 10% of them developed distant metastasis over a median follow-up period of 7 years. In multivariable analysis adjusting for age, stage, and subtype, transferrin saturation and serum iron were significantly associated with an increased risk of breast cancer metastasis. For each 10% increment of transferrin saturation at baseline, there was a 19% increase in metastatic risk (hazard ratio [HR] = 1.19; 95% confidence interval [CI] = [1.02-1.38]). Similarly, a serum iron increment of 10 µg/dL led to a 6% increase in risk (HR = 1.06; 95% CI = [1.01-1.12]). Ferritin was found not to be associated with metastatic risk (HR = 0.99; 95% CI = [0.98, 1.01]). There was no significant association with metastatic site or breast cancer subtype when adjusting for age and stage.

Conclusion: Elevated transferrin saturation and serum iron at early breast cancer diagnosis are associated with increased risk for metastatic disease but not with location of metastases or breast cancer subtype. Further research is needed to understand the underlying mechanisms and to explore the potential of iron-targeted therapies.

Background: Texture analysis has the potential to deliver quantitative imaging markers. Patients receiving computed tomography (CT)-guided percutaneous bone biopsies could be characterized using texture analysis derived from CT. Especially for breast cancer (BC) patients, it could be crucial to better predict the outcome of the biopsy to better reflect the immunohistochemistry status of the tumor.

Objectives: The present study examined the relationship between texture features and outcomes in patients with BC receiving CT-guided bone biopsies.

Design: This study is based on a retrospective analysis.

Methods: The present study included a total of 66 patients. All patients proceeded to undergo a CT-guided percutaneous bone biopsy, using an 11-gauge coaxial needle. Clinical and imaging characteristics as well as CT texture analysis were included in the analysis. Logistic regression analysis was performed to predict negative biopsy results.

Results: Overall, 33 patients had osteolytic metastases (50%) and 33 had osteoblastic metastases (50%). The overall positivity rate for the biopsy was 75%. The clinical model exhibited a predictive accuracy for a positive biopsy result, as indicated by an area under the curve (AUC) of 0.73 [95% confidence interval (CI) = 0.63-0.83]. Several CT texture features were different between Luminal A and Luminal B cancers; the best discrimination was reached for "WavEnHH_s-3" with a P-value of .002. When comparing triple-negative to non-triple-negative cancers, several CT texture features were different, the best discrimination achieved "S(5,5)SumVarnc" with a P-value of .01. For the Her 2 discrimination, only 3 parameters reached statistical significance, "S(4,-4)SumOfSqs" with a P-value of .01.

Conclusions: The utilization of CT texture features may facilitate a more accurate characterization of bone metastases in patients with BC. There is the potential to predict the immunohistochemical subtype with a high degree of accuracy. The identified parameters may prove useful in clinical decision-making and could help to identify patients at risk of a negative biopsy result.

Background: Ferroptosis is a recently studied form of programmed cell death characterized by lipid peroxides accumulation in the cells. This process occurs when a cell's antioxidant capacity is disturbed resulting in the inability of the cell to detoxify the toxic peroxides. Two major components that regulate ferroptosis are cysteine and iron.

Objective: This study aimed to determine the effect of cysteine deficiency and iron chelation on triple-negative breast cancer (TNBC) ferroptosis in a lipid-enriched microenvironment.

Design: The study has a laboratory-based experimental design. This study used the MDA-MB-231 cell line in various in vitro cell culture systems to investigate the research question.

Methods: For the first part of the study, we subjected MDA-MB-231 cells to grow in cysteine-absent adipocyte-conditioned media. In the second half, we treated MDA-MB-231 cells with iron chelator, deferoxamine. BODIPY imaging and western blot were carried out to observe ferroptosis in the cells under the 2 conditions.

Results: The results showed that cysteine absence in the conditioned media was able to reduce the formation of lipid droplets, which increased the greater access to free fatty acids to undergo oxidation, therefore inducing ferroptosis. On the contrary, cells when treated with deferoxamine along with erastin (ferroptosis-inducing drug), showed an increase in cell iron content was observed, later inducing ferroptosis.

Conclusion: Our results show an alternative function of cysteine and deferoxamine, one regulating lipid droplets and the other inducing ferroptosis, although an inhibitor of the same, respectively.

Background: Circulating rare cells participate in breast cancer evolution as systemic components of the disease and thus, are a source of theranostic information. Exploration of cancer-associated rare cells is in its infancy.

Objectives: We aimed to investigate and classify abnormalities in the circulating rare cell population among early-stage breast cancer patients using fluorescence marker identification and cytomorphology. In addition, we sought to determine the dependency of these markers on the presence of tumors.

Design: We evaluated the validity of a multi-rare-cell detection platform and demonstrated the utility of a specific rare cell subset as a novel approach to characterize the breast cancer system. Sampling was conducted both before and after tumor resection.

Methods: Linearity of the Rarmax platform was established using a spike-in approach. The platform includes red blood cell lysis, leukocyte depletion and high-resolution fluorescence image recording. Rare cell analysis was conducted on 28 samples (before and after surgery) from 14 patients with breast cancer, 20 healthy volunteers and 9 noncancer control volunteers. In-depth identification of rare cells, including circulating tumor cells, endothelial-like cells, erythroblasts, and inflammation-associated cells, was performed using a phenotype and morphology-based classification system.

Results: The platform performed linearly over a range of 5 to 950 spiked cells, with an average recovery of 84.6%. Circulating epithelial and endothelial-like cell subsets have been demonstrated to be associated with or independent of cancer with tumor presence. Furthermore, certain cell profile patterns may be associated with treatment-related adverse effects. The sensitivity in detecting tumor-presence and cancer-associated abnormality before surgery was 43% and 85.7%, respectively, and the specificity was 100% and 96.6%, respectively.

Conclusion: This study supports the idea of a cancer-associated rare cell abnormality to represent tumor entities as well as systemic cancer. The latter is independent of the apparent clinical cancer.

Introduction: Sentinel lymph node biopsy (SLNB) of the axilla is standard in breast cancer (BC) management; however, its role in prophylactic/contralateral prophylactic mastectomy (CPM) is still questioned. To avoid future consequences on surgical morbidity and socioeconomic aspects in low and middle-income countries (LMICs), we intend to determine the prevalence of occult breast cancer (OBC) among CPM cases.

Objective: To determine the prevalence of OBC in patients undergoing prophylactic mastectomy (PM).

Design: This is a retrospective cohort study.

Materials and methods: This retrospective cohort study is conducted at a tertiary-care hospital from January 2017 to December 2022. All individuals with the positive genetic test for high-risk breast cancer (HRBC) genes who underwent PMs/CPM at our centre were included. We analysed data using SPSS version 23.0.

Results: Twenty-six mutation-positive females underwent PM/CPM (16.1%). Two (7.69%) of 26 had later post-PM recurrence. Only 8 (30.76%) patients had SLNB and all were negative. No OBC was seen in PM/CPM specimens, whereas 3 (11.5%) had atypical ductal hyperplasia (ADH). Two of the ADH had BI-RADS-1, whereas 1 was BI-RADS-4 (33.3%) on the preoperative assessment. Results also showed that with an increase in the tumour grade of the diseased breast, the BI-RADS score of the asymptomatic breast was subsequently increased (P = .029).

Conclusion: Our study shows negative OBCs in PM/CPM cases with persistently negative SLNB results; however, ADH is identified in 11.5% of specimens. Our results suggest that SLNB can be safely omitted in patients undergoing CPM, but, preoperatively, patient and disease factors should be considered.

Background: Breast cancer remains the most common invasive cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. Trastuzumab (Tz) is typically used to treat HER2-positive breast cancers, but its potential in TNBC is unclear.

Objectives: To investigate the effects of trastuzumab on cell viability, apoptosis, cell cycle progression, and gene expression in TNBC cell lines compared with HER2-positive and normal cell lines.

Design: This is an in vitro experimental pre-clinical study using cultured cancer cell lines.

Methods: MDA-MB-231 and 4T1 (TNBC), MCF-7 (HER2-positive), and HSF (normal) cell lines were treated with 20 μg/mL trastuzumab for 24 hours. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis by flow cytometry, cell cycle progression by DNA content analysis, and gene expression by qPCR.

Results: Trastuzumab significantly reduced cell viability and induced apoptosis in TNBC cell lines, comparable to effects in HER2-positive MCF-7 cells. Cell cycle analysis revealed G2/M phase arrest in TNBC cells. Gene expression analysis showed upregulation of ERBB2, NOTCH1, EGFR, PIK3CA, and PTEN in MDA-MB-231 cells, while 4T1 cells exhibited downregulation of most genes except NOTCH1.

Conclusion: This study provides initial evidence for trastuzumab's potential therapeutic effects in TNBC, despite low HER2 expression. The observed cytotoxicity, apoptosis induction, and cell cycle modulation in TNBC cells warrant further investigation into trastuzumab's mechanisms of action in HER2-negative contexts and its potential repurposing for TNBC treatment.