Clinical breast cancer最新文献

Background: HER2-targeted therapies have significantly improved outcomes for patients with HER2-positive breast cancer (BC), which represents 15% to 20% of all BC cases. HER2 status is assessed via immunohistochemistry (IHC) and/or in situ hybridization (ISH), dividing BCs into five groups (G1-G5).

Patients and methods: In a study of 2,702 primary BC cases, comprising 12.7% G1, 0.2% G2, 2.8% G3, 8.5% G4, and 75.9% G5, we analyzed clinicopathologic features and HER2 protein expression digitally for each ISH group.

Results: Notably, G5 cases had a higher proportion of lobular carcinoma (13.9%) compared to other groups. G3 cases showed the highest percentage of grade 3 tumors (56.9%), while G5 cases had the lowest (21.4%). Additionally, G5 cases had the highest rate of estrogen receptor (ER) positivity (84.6%), while G1-HC (high copy number) cases had the lowest (70.4%). Most G1-HC cases were HER2 IHC 3+ (76.1%), while most G5 cases were IHC 0/1+ (75.7%). IHC 2+ was most common in G1-LC (low copy number) and G3 cases (83.8% and 90.7%, respectively), with G4 cases predominantly IHC 2+ (56.3%) and IHC 1+ (30.1%). Discordant HER2 IHC and ISH results were observed in 12 cases (0.4%), including 7 G1-HC (2.3%), 4 G1-LC (10.8%), and 1 G5 case (0.1%). Digital quantification of HER2 IHC levels in all groups except G5 revealed that G1-HC tumors had the highest HER2 protein expression, followed by G3, with G4 showing the lowest.

Conclusion: These findings offer valuable insights into the clinicopathologic characteristics and future management for different HER2 ISH groups.

Background: Coactivator associated arginine methyltransferase 1 (CARM1) has been identified as a regulator of breast cancer (BC) progression, yet the underlying mechanisms remain elusive.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA expression of CARM1 and solute carrier family 7 member 11 (SLC7A11). Western blotting was conducted to detect the protein expressions of CARM1, ubiquitin specific peptidase 4 (USP4), and SLC7A11. Cell viability, apoptosis, invasion, and migration were evaluated using CCK-8 assay, flow cytometry, transwell assay, and wound-healing assay, respectively. Fe²⁺ and GSH levels were determined by colorimetric assay. Fluorescence microscopy and flow cytometry were utilized to quantify reactive oxygen species (ROS) production. Co-immunoprecipitation (Co-IP) assay and cycloheximide (CHX) assay were performed to investigate the relationship between USP4 and CARM1. Xenograft mouse model assay was conducted to validate the effects of USP4 silencing and CARM1 overexpression on the malignant phenotypes of BC cells.

Results: CARM1 and SLC7A11 expression was upregulated in BC tissues and cells when compared with normal breast tissues and cells. Silencing of CARM1 inhibited the malignant phenotypes of BC cells, including decreased cell viability, invasion, and migration and increased cell apoptosis, ferroptosis and oxidative stress. In addition, USP4 stabilized CARM1 protein expression through its deubiquitinating activity. Overexpression of CARM1 attenuated the effects of USP4 silencing in both MCF-7 and MDA-MB-231 cells. Furthermore, silencing of CARM1 reduced SLC7A11 expression, and SLC7A11 overexpression relieved the CARM1 silencing-induced effects. Further, overexpression of CARM1 counteracted the inhibitory effects of USP4 silencing on tumor growth in vivo.

Conclusion: Our study reveals a novel mechanism by which USP4-dependent CARM1 promotes the malignant growth of BC cells by interacting with SLC7A11. Targeting this axis may provide a potential therapeutic strategy for BC.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that disproportionately affects younger females, non-Hispanic Black women, Hispanic women, and women with the BRCA1 gene mutation. Hereditary genetic testing is particularly important in this population to assess preventative and treatment strategies, however access to genetic testing is variable. A qualitative review was performed to evaluate barriers to genetic testing for patients with TNBC. Mutations common in breast cancer are reviewed along with updated guidelines on management strategies, including the ability to include PARP inhibitors as a treatment strategy. Barriers to genetic testing are multifactorial, with non-Hispanic Black women being tested less often than other groups. The disparity is even further represented by the limited number of non-Hispanic Black patients with TNBC who receive risk-reducing surgery or targeted systemic therapy. Eliminating barriers to genetic testing can allow us to support guideline-directed care for patients with TNBC at higher risk for genetic mutations.

Background: The relationship between the systemic immune-inflammation index (SII), chemotherapy sensitivity, and prognosis in HR+HER2- breast cancer (BC) has not been extensively studied.

Patients and methods: Clinical data from 980 patients diagnosed with HR+HER2- BC between June 2012 and June 2016 were collected. Patients were divided into low- and high-SII groups according to median SII value. Differences among variables were assessed using the chi-squared test. The inverse probability of treatment weighting (IPTW) method was used to control bias. The associations between clinicopathological factors, baseline SII, and disease-free survival (DFS) were analyzed using Kaplan-Meier curves and Cox analyses.

Results: The median follow-up period was 37 months (5-77). 480 patients underwent neoadjuvant chemotherapy, and low baseline SII values were associated with higher pathological complete response (pCR) rates than those in the high SII group (16.4% vs. 9.2%; P = .019). Multivariate analyses revealed that larger tumor size, more lymph node involvement, high Ki-67 score, and high baseline SII were independent prognostic factors for worse outcomes in patients with HR+HER2- BC. The risk for metastasis/recurrence was higher in the high SII group compared with that in the low SII group (hazard ratio 2.07 [95% CI, 1.35-3.19]; P = .001). After IPTW, a similar result was obtained, in that a high SII value was significantly associated with worse DFS among patients with HR+HER2- BC.

Conclusion: A low baseline SII was associated with higher pCR rates after neoadjuvant chemotherapy and was an independent prognostic factor for better DFS outcomes in patients with HR+HER2- BC.

Hyperglycemia is a common adverse event (AE) associated with phosphatidylinositol-3-kinase inhibitors (PI3Kis) and considered an on-target effect. Presence of hyperglycemia is associated with poor outcomes in patients with cancer, and there is need for further refinement of hyperglycemia prevention and mitigation strategies in patients receiving PI3Kis. In this review, the authors highlight effective strategies for preventing PI3Ki-induced hyperglycemia before and during treatment as well as hyperglycemia management. Prior to initiating treatment with PI3Ki, identify baseline risk factors of patients at increased risk for developing hyperglycemia, which include older age, obesity, and glycosylated hemoglobin (HbA1c) 5.7%-6.4% (prediabetes or Type 2 diabetes). To prevent new-onset hyperglycemia, optimize blood glucose, and recommend a low-carbohydrate (60-130 g/day) diet along with regular exercise to all patients prior to initiating the PI3Ki. Prophylactic metformin may be considered in all patients starting a PI3Ki with HbA1c ≤6.4%. Although existing recommendations support monitoring fasting blood glucose (FBG) once weekly (twice-weekly for intermediate-risk, daily for high-risk patients) and HbA1c every 3 months upon initiation of PI3Ki, more frequent FBG monitoring may be considered for prompt detection of hyperglycemia. Experts also recommend considering postprandial glucose monitoring because it is an early indicator of glucose intolerance. If hyperglycemia develops, metformin (first-line) and/or sodium glucose co-transporter 2 inhibitors or thiazolidinediones (second-/third-line) are the preferred agents; consider early referral to an endocrinologist. In conclusion, hyperglycemia is a common but manageable AE associated with PI3Kis. Multidisciplinary approach to the prevention, monitoring, and management of hyperglycemia optimizes patient care and allows patients to maintain therapy on PI3Ki.

Purpose: This meta-analysis aims to assess and compare the diagnostic effectiveness of [¹⁸F] FDG PET/CT and [¹⁸F] FDG PET/MRI for distant metastases in breast cancer patients.

Methods: A comprehensive search of the PubMed and Embase databases was performed to identify relevant articles until September 22, 2023. Studies were eligible to be included if they assessed the diagnostic performance of [¹⁸F] FDG PET/CT and/or [¹⁸F] FDG PET/MRI in detecting distant metastases of breast cancer patients. The DerSimonian and Laird method was used to assess sensitivity and specificity, and then transformed through the Freeman-Tukey double arcsine transformation.

Results: 29 articles consisting of 3779 patients were finally included in this study. The overall sensitivity of [¹⁸F] FDG PET/CT in diagnosing distant metastases of breast cancer was 0.96 (95% CI: 0.93-0.98), and the overall specificity was 0.95 (95% CI: 0.92-0.97). The overall sensitivity of [¹⁸F] FDG PET/MRI was 1.00 (95% CI: 0.97-1.00), and the specificity was 0.97 (95% CI: 0.94-1.00). The results suggested that [¹⁸F] FDG PET/CT and [¹⁸F] FDG PET/MRI appears to have similar sensitivity (P = .16) and specificity (P = .30) in diagnosing distant metastases of breast cancer.

Conclusions: The results of our meta-analysis indicated that [¹⁸F] FDG PET/CT and [¹⁸F] FDG PET/MRI in diagnosing distant metastases of breast cancer appear to have similar sensitivity and specificity. Patients who have access to only one of these modalities will not have the accuracy of their staging compromised. In clinical practice, both of these imaging techniques have their respective strengths and limitations, and physicians should take these into account when making the most suitable choice for patients.

Introduction/background: This study estimates the percentage of detectable breast cancers in the screening population that could be found with primary and supplemental screening, and provides cost estimates for population wide supplemental screening in the U.S.

Materials and methods: Published estimates on cancer detection rates of 2D mammography, tomosynthesis (DBT), whole breast ultrasound (US), molecular breast imaging (MBI), contrast-enhanced mammography (CEM), and MRI, the number of mammograms conducted in the United States in 2023, and the proportion of dense breast tissue, were utilized. The maximum number of detectable cancers was projected from incremental cancer detection rates of the most sensitive supplemental screening method. The proportion of cancers detectable for each modality was calculated. In 2023, Medicare reimbursement rates were used to estimate supplemental screening costs.

Results: Out of 469,437 detectable cancers, 2D mammography could detect 190,531 (41%), leaving 278,906 undetected. Adding supplemental screening could detect a combined 220,165 cancers (47%) with DBT, 237,596 (51%) with US, 331,727 (71%) with MBI, 377,049 (80%) with CEM and 469,437 (100%) with MRI. The imaging cost in US dollars to provide supplemental screening to all individuals with dense breasts in 2023 was $933M for tomosynthesis, $1.84B for US, $3.87B for CEM, $4.16B for MBI, and $6.36B for MRI.

Conclusion: The study highlights potential benefits from supplemental breast cancer screening, suggesting the combination of mammography and breast MRI offers the most effective detection method though at the highest imaging cost. These findings provide valuable insights to guide future research and inform decision-making in supplemental breast cancer screening strategies.

Background: Breast cancer is the most frequently diagnosed cancer among women worldwide with high morbidity and mortality. Previous studies have indicated that RNA-binding motif protein-15 (RBM15), an N6-methyladenosine (m6A) writer, is implicated in the growth of breast cancer cells. Herein, we aimed to explore the function and detailed mechanism of RBM15 in breast cancer.

Methods: In this research, UALCAN databases were applied to analyze the expression of RBM15 or Karyopherin-2 alpha (KPNA2) in BRCA. RBM15 and KPNA2 mRNA levels were determined using real-time quantitative polymerase chain reaction (RT-qPCR) assay. RBM15, KPNA2, and Programmed cell death ligand 1 (PD-L1) protein levels were measured using western blot. Cell proliferation, migration, and invasion were assessed using 5-ethynyl-2'-deoxyuridine (EdU) and Transwell assays. The biological role of RBM15 on breast cancer tumor growth was verified using the xenograft tumor model in vivo. Effects of breast cancer cells on the proliferation and apoptosis of CD8⁺ T cells were analyzed using flow cytometry. Interaction between RBM15 and KPNA2 was validated using methylated RNA immunoprecipitation (MeRIP) and dual-luciferase reporter assays.

Results: RBM15 and KPNA2 were highly expressed in breast cancer tissues and cell lines. Furthermore, RBM15 silencing might suppress breast cancer cell proliferation, migration, invasion, and lymphocyte immunity in vitro, as well as block tumor growth in vivo. At the molecular level, RBM15 might improve the stability and expression of KPNA2 mRNA via m6A methylation.

Conclusion: RBM15 might contribute to the malignant progression and immune escape of breast cancer cells partly by modulating the stability of KPNA2 mRNA, providing a promising therapeutic target for breast cancer.

Background: To develop and validate a model based on conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) features to preoperatively predict microinvasion in breast ductal carcinoma in situ (DCIS).

Patients and methods: Data from 163 patients with DCIS who underwent CUS and CEUS from the internal hospital was retrospectively collected and randomly apportioned into training and internal validation sets in a ratio of 7:3. External validation set included 56 patients with DCIS from the external hospital. Univariate and multivariate logistic regression analysis were performed to determine the independent risk factors associated with microinvasion. These factors were used to develop predictive models. The performance was evaluated through calibration, discrimination, and clinical utility.

Results: Multivariate analysis indicated that centripetal enhancement direction (odds ratio [OR], 13.268; 95% confidence interval [CI], 3.687-47.746) and enhancement range enlarged on CEUS (OR, 4.876; 95% CI, 1.470-16.181), lesion size of ≥20 mm (OR, 3.265; 95% CI, 1.230-8.669) and calcification detected on CUS (OR, 5.174; 95% CI, 1.903-14.066) were independent risk factors associated with microinvasion. The nomogram incorporated the CUS and CEUS features achieved favorable discrimination (AUCs of 0.850, 0.848, and 0.879 for the training, internal and external validation datasets), with good calibration. The nomogram outperformed the CUS model and CEUS model (all P < .05). Decision curve analysis confirmed that the predictive nomogram was clinically useful.

Conclusion: The nomogram based on CUS and CEUS features showed promising predictive value for the preoperative identification of microinvasion in patients with DCIS.

Introduction: Breast cancer is the most common malignancy in women of reproductive age and chemotherapy protocols impair fertility, frequently necessitating fertility preservation (FP) referral. Embryo, oocyte, or ovarian tissue cryopreservation are established FP modalities in women with breast cancer but there are few data on their uptake over time. In this study our aim was to determine the regional time trends and utility differences for fertility preservation methods of reproductive tissue cryopreservation.

Methods: This multicenter study included 1623 women diagnosed with breast cancer from 7 tertiary centers in 6 countries (Brazil, Italy, Scotland, South Korea, Turkey, USA). Participant centers provided the details of FP cryopreservation approaches broken down annually from 2012 to 2021. Women with newly diagnosed breast cancer, aged 18-45 years who were referred for FP at participating centers and had normal ovarian function at the time were included.

Results: We found a mean increase of 7% per year (P = .002, adjusting for centers) in the number of women referred for FP. Of those who were referred (n = 1623), a mean 38.7% underwent FP (n = 629), with a range of 12% in South Korea) to 95% in Brazil. The number of women undergoing ovarian stimulation for FP continually increased until 2021, with oocyte cryopreservation being the most common procedure throughout the study period (P = .014 for time trend). The proportion of random start ovarian stimulation cycles increased each year from 58.3% in 2012 to 86.8% in 2021, (P = .005 for time trend, and P = .04 for 2012 vs. 2021).

Conclusions: The utility of FP has steadily increased for young women with breast cancer over the last decade, although regional differences significantly influence FP practices. The findings of our study could have value for policy making in FP care for young women with breast cancer at the local, regional, or global level.