Clinical breast cancer最新文献

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.

Aim: To evaluate the role of Indocyanine Green Lymphography (ICG_L) in the early diagnosis and personalized management of breast cancer-related lymphedema (BCRL) among high-risk breast cancer (BC) survivors.

Methods: Patients who admitted to the UPMC Magee-Womens Hospital Lymphedema Program between October 2018 and December 2021 with episodic symptoms were enrolled into the study. Patient demographics, clinical characteristics, and outcomes were prospectively collected and retrospectively analysed. Lymphatic flow disruptions were identified and guided personalized therapeutic interventions were guided by ICG_L.

Results: Among 154 BC survivors, 184 arms were evaluated. Initial ICG_L showed 57.1% had no lymphedema, while 42.9% were classified as stage 1 to 3 lymphedema. Early diagnosis and personalized interventions provided improved outcomes, with only 4.3% developing clinical lymphedema after a median follow-up of 27 months. Patients exhibited stable or improved symptoms with individualized treatments such as manual lymphatic drainage, compression therapies, and physiotherapy.

Conclusion: ICG_L evaluation is essential for patients at high-risk of developing BCRL. Early diagnosis before clinical onset of lymphedema, and ICG_L guided therapy significantly enhances the clinical outcomes and improves lymphedema management.

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.

Introduction: We sought to develop clinical guidelines within our multidisciplinary Breast Center to support decision-making for managing high-risk breast lesions. The objective is to describe the process used to develop these guidelines and assess perceived acceptability.

Methods: We recruited clinical stakeholders to identify key "high-risk" topics. Stakeholder groups (surgery, radiology, pathology) met separately to review the topics, leveraging existing literature reviews and best available evidence. Guidelines were initially developed in 2015 and updated in 2019. We surveyed breast clinical team members in 2023 regarding the perceived acceptability of the guidelines and summarized the data.

Results: We created clinical guidelines to address the management of atypical ductal hyperplasia, flat epithelial atypia, atypical lobular hyperplasia/lobular carcinoma in situ, radial scar/complex sclerosing lesion, and papillomas. Key guideline components included process for radiologic-pathologic correlation, patient disposition after biopsy (surgical referral needed, follow-up imaging recommended), recommendation for the role of surgical excision, and recommendation regarding imaging follow-up if excision not performed. Forty clinical team members (66% [40/60] response rate) completed the acceptability survey from varied disciplines. Most (78%) were aware of the guidelines. Respondents rated the recommendations for disposition after biopsy, surgical management, and follow-up imaging as the most helpful components. Most (> 80%) rated them to be very/extremely useful.

Conclusion: We leveraged input from key stakeholders to develop clinical guidelines to support the multidisciplinary management of patients with high-risk breast lesions. Our guidelines have been successfully implemented across our academic and community practice. Future steps will assess the impact of implementation on clinical outcomes.

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.

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.

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: It is unclear whether breast cancer (BC) subtypes or CSF cytology results are associated with overall survival (OS) among patients with BC leptomeningeal disease (LMD). This single-institution retrospective study compares OS among BC patients with LMD across various breast cancer subtypes and CSF cytology results.

Methodology: The study enrolled BC patients diagnosed with LMD between 2010 and 2023. Breast cancer subtypes were classified as A. ER+/HER2-, HER2+, or triple-negative BC (TNBC); B. HER2+, HER2-Low, HER2-Zero. CSF cytology subtypes included CSF+, CSF-, or CSF not tested (NT). OS was summarized via Kaplan-Meier analysis and compared using log-rank test. Cox models were used for multivariate analyses.

Results: Out of 69 patients registered, median OS (95% CI) for ER+/HER2- (n = 33), HER2+ (n = 12) and TNBC (n = 24) subtypes were 8.0 (3.02, 24.8), 5.71 (1.61, not estimated) and 3.2 (1.11, 4.95) months (P = .17). In multivariate analysis, TNBC was associated with worse OS versus ER+/HER2- [Hazard Ratio (HR), 95% CI: 2.64, 1.23-5.80, P = .04]. HER2 subtypes (HER2-Zero, n = 21; HER2-Low, n = 32; HER2+, n = 12) showed no significant differences in OS. Median OS (95% CI) for CSF+ (n = 16), CSF- (n = 18), and CSF NT (n = 35) groups were 3.54 (1.61, 12.72), 13.41 (4.95, 61.93) and 3.28 (1.44, 6.92) months (P = .04). Multivariate analysis showed both CSF+ and CSF NT were associated with shorter OS compared to CSF- group [HR (95% CI) 4.50 (1.75, 12.11) for CSF+ vs. CSF-; 2.91 (1.45, 6.26) for CSF NT vs. CSF-; P = .002].

Conclusion: TNBC LMD group was associated with worse OS than ER+/HER2- BC LMD when adjusting for other prognostic factors. CSF- LMD patients had better OS than CSF+ or CSF NT LMD.