Clinical breast cancer最新文献

Background: Data are needed to improve the current understanding of the epidemiology of patients with high-risk, HER2-negative, early breast cancer (eBC) (hormone receptor positive [HR+]/HER2-negative BC and triple-negative BC [TNBC]).

Patients and methods: This retrospective longitudinal cohort study used real-world, population-level data that included all individuals newly diagnosed with high-risk, HER2-negative eBC in Alberta, Canada, between 2010 and 2019. Data on treatment, laboratory results and pathology findings were collected through electronic health records and administrative databases.

Results: The annual cumulative incidence of high-risk, HER2-negative eBC ranged from 6% to 9% of all incident BC cases. Individuals with TNBC were more likely to be younger, had stage II disease, grade 3 histology and received systemic therapy at a community centre (P < .05) compared to individuals with HR+/HER2-negative eBC. Only 14% of individuals diagnosed in 2010-2017 underwent germline BRCA testing postdiagnosis. Neoadjuvant systemic therapy was given to 37% of individuals. Adjuvant systemic therapy use increased from 77% (2012-2015) to 84% (2019). The 5-year overall survival (OS) from initiation of adjuvant systemic therapy or date of surgery (for individuals who did not receive adjuvant systemic therapy) was 77% (95% CI: 75-79). OS was significantly worse among individuals who were older, had grade 3 histology, had stage III disease, or had nodal involvement (P < .05). OS among individuals with TNBC between 2016 and 2019 who initiated adjuvant capecitabine was markedly worse compared to the overall cohort (2-year OS: 70% vs. 89%).

Conclusion: Outcomes analyses in this high-risk, HER2-negative eBC population suggest a continued unmet clinical need.

Background: The appropriateness of BCT for MF/MCBC is debated, with concerns about higher recurrence rates. This study aims to provide an updated systematic review and meta-analysis of LR and survival outcomes for MF/MCBC patients undergoing BCT.

Methods: PubMed, Web of Science, Embase, and the Cochrane Library were searched up to May 2024. Eligible studies included original research articles comparing LR, DFS, or OS in patients with MF/MC or UF breast cancer undergoing BCT or mastectomy. Meta-analyses for LR were conducted using the Mantel-Haenszel method. Published Kaplan-Meier curves for DFS and OS were digitized and aggregated to estimate summary survival curves.

Results: 21 studies were included in the meta-analysis for LR, comprising 28,589 participants, and 7 studies for survival analysis. The meta-analysis revealed that MF/MC breast cancer patients undergoing BCT had a significantly higher LR rate compared to UF patients (OR = 1.76, 95% CI: 1.24-2.49, P = .002), though recent studies indicated comparable LR rates. No significant difference in LR was found between MF/MC patients treated with BCT versus mastectomy (OR = 1.72, 95% CI: 0.96-3.10, P = .07). The estimated 3-, 5-, and 8-year DFS rates were 92.4%, 88.3%, and 84.5%, respectively, while the OS rates were 98.0%, 95.8%, and 91.8%.

Conclusion: BCT for MF/MC breast cancer was associated with higher LR rates compared to UF breast cancer, but the disparity was reducing in recent years. BCT offers comparable LR outcomes to mastectomy in MF/MC patients. Survival outcomes for MF/MC patients treated with BCT were favorable, affirming its oncological safety.

Purpose: This study evaluates real-world outcomes, toxicities, and prescribing patterns of PARP inhibitors (PARPis) for the treatment of metastatic breast cancer (MBC).

Patients and methods: Electronic health records of 62 MBC patients treated with olaparib (n = 48) or talazoparib (n = 14) at Mayo Clinic System between 2017 and 2022 were analyzed. Time-to-treatment-failure (TTF) was assessed utilizing the Kaplan-Meier method. Predictors of TTF were identified in a multivariate Cox-proportional hazard regression model adjusting for relevant tumor and demographic characteristics.

Results: Among 62 patients who received PARPis for MBC, 55 had germline (g) pathogenic variants (PVs) (gBRCA1 = 24, gBRCA2 = 26, and gPALB2 = 4) and 8 patients had somatic (s) PVs (sBRCA1 = 4, sBRCA2 = 2, sATM = 1, sCDKN2A = 1). Median TTF in the gBRCA1, gBRCA2, and gPALB2 PV carriers were 7, 8, and 9 months, respectively (P = .37). Complete or partial responses were observed among 51.8% of patients with gBRCA or gPALB2 PVs. In multivariate analysis, HER2 positivity (hazard ratio, HR: 4.9, P = .007) and somatic PVs in homologous recombination repair (HRR) genes other than BRCA (sATM or sCDKN2A) (HR: 11.7, P = .01) were associated with a shorter TTF. No significant difference in TTF was observed by the type of PARPi, estrogen and progesterone receptor status, age, or number of prior therapies. Eight (16.7%) patients receiving olaparib and seven (50%) receiving talazoparib required dose reductions due to toxicities.

Conclusions: In real-world practice, PARPis are well-tolerated with promising TTF in gBRCA1/2 and gPALB2 carriers. Further studies will delineate the clinical efficacy of PARPis in other MBC subsets, such as sBRCA mutations, HER2-positive disease, and CNS metastasis.

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.

Therapy directed against human epidermal growth factor receptor type 2 (HER2) is the standard of care for patients with early-stage and metastatic HER2-positive breast cancer. Treating patients with HER2-positive breast cancer with anti-HER2-monoclonal antibodies, specifically trastuzumab and pertuzumab, is considered standard of care in the neoadjuvant and adjuvant settings and in the first-line setting for metastatic HER2-positive breast cancer. Pertuzumab and trastuzumab are commonly administered intravenously. Subcutaneous (SC) formulations of trastuzumab alone and as a combined product of pertuzumab and trastuzumab are now available for clinical use. Phase III trial results demonstrate that the efficacy and safety of SC trastuzumab and fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf for subcutaneous (PH FDC SC) injection and the intravenous (IV) formulation counterparts are comparable. SC formulations of anti-HER2 monoclonal antibodies offer several advantages over IV counterparts, including shorter administration time, less need for IV access, and better resource utilization for treatment facilities. This review summarizes the clinical data supporting the use of SC trastuzumab and PH FDC SC injection in treating early-stage and metastatic HER2-positive breast cancer and highlights the benefits of SC injection compared to the IV formulations.

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.

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.