International Journal of Breast Cancer最新文献

Background: Breast cancer is a leading cause of cancer-related morbidity and mortality in women worldwide. Among its subtypes, triple-negative breast cancer (TNBC) poses the greatest therapeutic challenge due to its aggressive nature and lack of targeted treatments. Holocytochrome c synthase (HCCS), a mitochondrial enzyme essential for cytochrome c maturation, may play a pivotal role in cancer pathogenesis.

Objective: This study aimed to investigate the expression profile, epigenetic regulation, immune interactions, prognostic significance, and molecular networks of HCCS across cancers, with a particular focus on breast cancer and its subtypes.

Methods: Publicly available datasets and bioinformatics tools were employed to analyze HCCS expression, methylation, survival outcomes, immune infiltration, and interaction networks. Expression and clinical outcomes were examined using TCGA, while methylation and expression patterns were assessed via UALCAN and TNMplot. Survival analyses were performed using Kaplan-Meier Plotter, and immune infiltration was evaluated with TIMER2.0. Protein-protein interaction networks were generated with STRING, and functional enrichment was conducted through g:Profiler. Key findings were validated in independent breast cancer cohorts from GEO and the GOBO platform.

Results: HCCS was significantly overexpressed in multiple cancers, with the highest upregulation observed in breast cancer, particularly TNBC. Hypomethylation of the HCCS promoter was associated with increased expression. High HCCS expression correlated with poorer relapse-free survival and greater immune infiltration, including CD4⁺ T cells, CD8⁺ T cells, macrophages (M1/M2), mast cells, and regulatory T cells. Protein-protein interaction analysis revealed HCCS-associated genes enriched in mitochondrial and apoptotic pathways. Validation across independent datasets consistently supported the association of elevated HCCS expression with poor prognosis in breast cancer.

Conclusion: This integrated bioinformatics analysis highlights HCCS as a potential prognostic biomarker and therapeutic target in breast cancer, particularly in TNBC, although further experimental validation is required before clinical application.

Purpose: HER2-low status is a predictive factor for novel anti-HER2 therapies in metastatic hormone receptor-positive breast cancer (HR+ MBC). However, its impact on endocrine therapy outcomes remains uncertain. We aimed to explore the effect of HER2-low and HER2-zero status in HR+ MBC patients treated with first-line aromatase inhibitors (AIs) with or without CDK4/6 inhibitors (CDK4/6i).

Methods: We retrospectively reviewed postmenopausal women with HR+ MBC treated with first-line AI ± CDK4/6i between January 1, 2017, and December 31, 2022, from six tertiary hospitals in Thailand. HER2-low was defined as HER2 IHC 1+ or IHC 2+ with ISH-negative. Progression-free survival (PFS) and overall survival (OS) were compared in unadjusted and adjusted cohorts using stabilized inverse probability of treatment weighting (sIPTW), adjusting for age, ECOG performance status, de novo metastasis, endocrine sensitivity, visceral metastasis, number of metastatic sites, and treatment year. Interaction analyses were performed to assess effect modification by HER2 status and other clinical subgroups.

Results: Among 504 patients, 219 (43.5%) were HER2-low, and 285 (56.5%) were HER2-zero. Median follow-up was 31 months (IQR 19-47). CDK4/6i + AI was administered to 52.5% of HER2-low and 43.9% of HER2-zero patients. After sIPTW adjustment, CDK4/6i + AI prolonged median PFS to 22.1 months compared with 21.5 months for AI alone in the HER2-low cohort (HR = 0.80, 95% CI 0.54-1.18; p = 0.26) and to 20.1 months compared with 13.5 months in the HER2-zero cohort (HR = 0.65, 95% CI 0.45-0.93; p = 0.02). Median OS was 49.3 months with CDK4/6i + AI versus 48.4 months with AI alone in HER2-low (HR = 0.81, 95% CI 0.48-1.36; p = 0.43) and 45.8 versus 42.3 months in HER2-zero (HR = 0.85, 95% CI 0.43-1.05; p = 0.52). Subgroup analyses showed consistent benefit of CDK4/6i + AI across most clinical categories. The interaction test for treatment × HER2 status was not significant (HR = 1.21, 95% CI 0.74-1.98; p = 0.44), indicating no effect modification by HER2-low status.

Conclusions: HER2-low status was not associated with prognosis or predictive value for CDK4/6i efficacy, supporting CDK4/6i + AI as the standard first-line therapy irrespective of HER2 expression level.

Patients with advanced HR+/HER2- breast cancer often experience prolonged disease courses, with bone being a dominant site of metastasis. Bone-targeted agents (BTAs) are recommended to reduce the risk of skeletal-related events (SREs), yet most clinical trials report follow-up durations of less than 2 years. Here, we present two cases of patients with breast cancer and bone metastases who received continuous BTA therapy for 8 and 10 years, respectively, in the context of ongoing antitumor treatment. Neither patient developed SREs during follow-up. The two cases demonstrated good tolerabilit during long-term treatment, though broader conclusions regarding safety require further investigation.

Breast cancer is one of the most common malignancies and the leading cause of cancer-related mortality among women worldwide, with hormone receptor-positive (HR+) breast cancer being the most common subtype. Current guidelines recommend endocrine therapy as the first-line treatment for HR+, human epidermal growth factor Receptor 2-negative breast cancer. In this case report, we describe a patient with HR+ breast cancer who developed bone and liver metastases after breast cancer surgery. We document the disease progression from initial treatment to managing local recurrence and treating distant metastasis using salvage chemotherapy combined with endocrine therapy. Importantly, following denosumab treatment, the patient experienced a bone flare; this presented as increased radionuclide uptake on bone scans, but was later confirmed as pseudoprogression. Furthermore, we note changes in the patient's pathology as the disease progresses.

Background: Breast cancer screening and effective neoadjuvant treatments have increased surgeries for nonpalpable tumors, often requiring preoperative localization. The wire-guided method, performed on the same day as surgery, has limitations, prompting interest in wire-free alternatives like magnetic seed devices. Methods: A retrospective single-center study (November 2020-March 2024) compared magnetic seed and wire-guided localization in 558 patients. The primary aim was to assess localization and retrieval success, resection margins, and reoperation rates. Secondary endpoints included the interval between localization and surgery, operative time, incision site selection, and volume excised. Results: Among 558 patients, 188 underwent magnetic seed and 370 wire-guided localizations. Both groups were similar in BMI, breast size, and lesion characteristics. Complications in the wire-guided group included device migration (0.5%) and hematoma (1.3%). Success rates were comparable (98.9% vs. 99.7%), as were positive margins (5.3% vs. 6.7%) and reoperation rates (6.9% vs. 7.8%). Excised volume was significantly lower in the magnetic seed group (24.2 [range 6.5-48.0 cm³] vs. 41.5 cm³ [range 16.0-68.0 cm³], p < 0.001). The magnetic seed group had an average localization-to-surgery interval of 1 day (range 0-160 days). Conclusions: Magnetic seed localization is as safe and effective as wire-guided localization, with comparable success rates and resection margins adequacy. Its primary advantage is scheduling flexibility, offering a longer interval between localization and surgery.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating complication of cancer treatment, particularly with agents like paclitaxel. Effective preventive measures for CIPN are limited. Metformin, an antihyperglycemic agent with neuroprotective properties, has shown promise in preclinical studies; however, its clinical utility in preventing CIPN remains underexplored. Objective: This study evaluates the preventive effects of metformin on paclitaxel-induced peripheral neuropathy in breast cancer patients. Methods: A randomized, controlled study was conducted involving 60 breast cancer patients receiving paclitaxel chemotherapy. Patients were assigned to an intervention group receiving metformin (500 mg twice daily) or a control group without metformin. Peripheral nerve function was assessed using nerve conduction studies (NCSs), measuring sensory nerve action potential (SNAP) amplitude, compound muscle action potential (CMAP) amplitude, and distal latency (DL). Clinical neurological symptoms and adverse effects of metformin were monitored throughout the study. Results: Of the 60 enrolled patients, 47 completed the study (26 control and 21 intervention). The incidence of CIPN was lower in the metformin group compared to the control group, although this difference did not reach statistical significance. Metformin was well-tolerated, with mild gastrointestinal side effects being the most common adverse events. No significant differences between the groups were observed in SNAP amplitude, CMAP amplitude, or DL. Conclusion: Metformin may modestly reduce the incidence of CIPN in patients receiving paclitaxel chemotherapy, although the observed effect was not statistically significant. Given its safety profile and potential neuroprotective benefits, metformin warrants further investigation in larger, multicenter trials to confirm its role in CIPN prevention.

Objectives: This study is aimed at evaluating androgen receptor (AR) and tumor-associated neutrophil (TAN) expressions in different breast cancer subtypes and their relationship with tumor differentiation, stage, and other clinicopathological markers. Methods: A cross-sectional study was conducted on 84 breast cancer patients at Stages I-IV. Tumor tissues were assessed using immunohistochemistry for ER, PR, HER2, AR, and Ki67, along with TAN evaluation using hematoxylin and eosin staining. Associations between AR, TAN, and other clinical variables were analyzed using chi-square, t-tests, and logistic regression. Results: AR was expressed in 70.2% of tumors and was significantly associated with ER positivity (OR = 74.31, p < 0.001), PR positivity (OR = 6.8, p = 0.01), and better differentiation (OR = 0.1 for poorly differentiated tumors, p = 0.035). AR positivity was highest in Luminal A/B subtypes (82%) and lowest in triple-negative breast cancer (TNBC) (20%; OR = 0.06, 95% CI: 0.01-0.3). In contrast, TAN positivity was observed in 45.6% of cases and was most frequent in TNBC (67%; OR = 3.7, 95% CI: 0.9-15.3) and poorly differentiated tumors (71.4%). TANs were inversely associated with PR positivity (OR = 0.21, p = 0.014) and showed a significant association with vascular invasion (p = 0.047). No significant associations were found between AR or TAN expression and metastatic status or neural invasion. Conclusion: AR is a defining marker for HR-positive breast cancers and may serve as an indicator of lower tumor grade and differentiation status. TANs, however, are linked to more aggressive phenotypes, especially in TNBC, suggesting a role in driving tumor progression. This highlights the potential for AR and TAN expression patterns to refine patient stratification across breast cancer subtypes.

Background: Breast cancer (BRCA) remains a leading cause of cancer-related mortality among women. CCL18 and EGF are implicated in tumor biology; however, their roles in BRCA remain partly defined. This study investigates their expression profiles, immune associations, prognostic relevance, epigenetic regulation, and molecular networks. Methods: Expression data from TCGA, UALCAN, and GSCA were analyzed to compare CCL18 and EGF levels in BRCA and normal tissues. Immune infiltration was assessed using TIMER, while survival analyses were performed via Kaplan-Meier plotter and TCGA subcohorts, including menopausal status. Promoter DNA methylation was examined using UALCAN. Gene correlation networks and protein-protein interactions were assessed using UALCAN and STRING. Result: CCL18 was significantly upregulated in BRCA tissues, while EGF showed no consistent increase compared to normal tissue. Both genes were strongly correlated with immune cell infiltration. High CCL18 and EGF expression was associated with reduced relapse-free survival in BRCA. Promoter regions of both genes exhibited reduced DNA methylation, supporting their elevated expression in tumors. Interaction analyses revealed distinct immune- and signaling-related gene and protein networks. Conclusion: CCL18 shows strong prognostic and immunological relevance in BRCA, while EGF appears to play a broader oncogenic role. Hypomethylation of both genes may drive their aberrant expression and involvement in tumor progression.

Background: The study was aimed at measuring the factors contributing to the delayed presentation of breast cancer patients within the socio-ecological context by developing a scale. Methods: The study objectives were measured by developing the items on the basis of a 5-point scale named the Socio-Ecological Scale for Breast Cancer Patients (SES-BCP). The dimensionality of the measure and internal consistency were determined by collecting data from 350 breast cancer patients from five main hospitals in three main cities (Lahore, Multan, and Faisalabad) in the Punjab province of Pakistan. A multistage sampling technique was employed, and sociodemographic factors were kept in consideration. Confirmatory factor analysis was applied for the factor structure in the study by using a structural equation model. Results: With the distinctive five factors of the SES-BCP, a total of 51 items were confirmed in the final scale with sound psychometric properties, providing a multidimensional view of the study that helps in the early detection and cure of disease. Conclusions: It can be concluded that this scale is a valuable addition to assess the underlying factors of delayed presentation in patients with breast cancer in the context of the socio-ecological model in Pakistan.

Introduction: The practice of mammography has transitioned from analog to digital with improved accuracy and significant changes to findings. This study was aimed at investigating the current patterns of breast diseases among women presenting for mammography at a major hospital in the Volta region of Ghana. Methods: This descriptive retrospective study reviewed 508 mammography and complimentary breast ultrasound reports conducted between October 2019 and May 2023. Because they were incomplete and had essential patient data missing, 28 reports (n = 28) were excluded. Data extracted from the reports included patients' age, clinical indication, breast density, imaging impression, and BI-RADS classification for each breast. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) Version 26, and results are presented using descriptive and inferential statistics. Results: The study involved 480 women, aged 40-86 years (mean = 54.6 ± 10.1). The distribution of the breast densities of the women was as follows: almost entirely fatty (n = 79, 16.46%), scattered areas of fibroglandular density (n = 226, 47.08%), heterogeneously dense (n = 145, 30.21%), and extremely dense (n = 30, 6.25%). There was a statistically significant association between age and breast density (p < 0.01). While 30 (6.25%) of the women presented for screening, 450 (93.75%) presented for diagnostic mammography. Breast pain (n = 189, 39.38%), breast lump/mass (n = 155, 32.29%), and suspected breast cancer (n = 47, 9.79%) were the most common clinical indications. The study recorded a total of 960 BI-RADS classifications of which 261 (27.19%) were negative and 699 (72.81%) were positive. Most of the positive findings (n = 521, 74.54%) were BI-RADS 2 and 3. Both benign and suspicious for malignancy or highly suggestive of malignancy lesions were common across women aged 40-50 years. There was a statistically significant association between age and BI-RADS classification (p < 0.01). Conclusion: This study showed that most of the women presented for diagnostic mammography. Attendance for screening mammography was poor among women presenting for mammography at the hospital; hence, women should be encouraged through health education and other campaign strategies to undergo screening mammography more regularly to facilitate more timely detection and diagnosis of breast diseases. A third of the women in our study had dense breasts. The vast majority of the women had positive findings, but the majority of these findings were indicative of benign breast diseases.