HR positive

We achieved a remarkable response in the metastatic lesions with minor toxicity issues. This case highlights the importance of utilizing up-to-date therapeutic agents and reactive decision-making during personalized cancer treatment.

Finally, sTIL levels were significantly higher in lung and axillary lymph node metastases compared to all metastases. While these analyses were conducted on multiple metastases obtained at the end of life after several lines of treatment, the data provides novel and valuable insights into the state of immune infiltration in patients with metastatic HR+/HER2- BC.

Endocrine therapy plus CDK 4/6i represents an effective treatment, regardless of HER2 status (low/zero). Second-line agents did not differ significantly in terms of TTD. Endocrine resistant cancers exhibit poor response to CDK 4/6i.

This result was superior to the second-line treatment with nab-paclitaxel, which resulted in a PFS of 8 months and best overall response of stable disease with slight shrinkage. The present case indicates that a combination of utidelone with apatinib/anlotinib exhibited antitumor activity in a patient with HR+/HER2- mBC with BMs. Therefore, this combination offers a promising therapeutic option for the clinical treatment of patients with breast cancer and BMs.

Tissue compartment and hormone receptor status differences in the effect of TGM2 expression on clinical outcomes of breast cancer may reflect the different functions of TGM2.

Dose reduction of CDK4/6 inhibitors within the first 12 weeks of treatment was associated with significantly higher mortality and shorter treatment duration. These findings contrast with previous analyses showing no effect of dose reduction, likely due to considering immortal time bias in this study.

These findings support current guidelines and advocate for the inclusion of everolimus in treatment plans for patients with metastatic HR+/HER2- breast cancer, particularly in late-line treatment, with careful consideration of the benefit-risk profile for each patient.

Clinical sample analyses revealed notably elevated expression levels of ZNF260 in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2-) BC tissues compared to adjacent non-tumor tissues (all P < 0.001). Reduction in ZNF260 expression was shown to inhibit the proliferation, clonogenicity, migration, and invasiveness of MCF-7 cells while concomitantly enhancing apoptosis (all P < 0.001).This investigation uniquely uncovered ZNF260 as a novel key gene, suggesting its potential utility as a predictive biomarker associated with m6A modifications specifically in HR + /HER2- BC.

Our findings should be used to guide breast cancer management policies in Morocco. Larger cohort studies are needed to determine the specificity of the breast cancer profile in Morocco as well as the epidemiological risk factors specific to every subtype.

To identify biomarkers associated with CDK4/6 inhibitor response or resistance, we combined bioinformatic-database analyses, artificial intelligence-assisted literature review, and manual literature review (Embase and OVID Medline; search window: January 2012-October 2022) to compile data to comprehensively describe the CDK4/6 inhibitor biomarker landscape. Based on these results, and validation by external experts, we identified 15 biomarkers of clinical importance (AR , AURKA, ERBB2, ESR1, CCNE1, CDKN1A/B, CDK2, CDK6, CDK7, CDK9, FGFR1/2, MYC, PIK3CA/AKT, RB1 and STAT3) that could guide future breast cancer research.

In preclinical models, the postbiotics tyramine could reverse the MAP3K1 mutation-induced MHC-I reduction, thereby augmenting the efficacy of immunotherapy. Collectively, our study identified the vital biomarker driving the immunological heterogeneity of HR+/HER2- breast cancer and elucidated the underlying molecular mechanisms, which provided the promise of tyramine as a novel therapeutic strategy to enhance the efficacy of immunotherapy.

Several clinical trials have validated the efficacy and safety of trastuzumab deruxtecan (T-Dxd) in HER2-low breast cancer at different treatment settings...The discussion mainly focused on the precise diagnosis of HER2-low breast cancer, treatment design at different disease status, regimens selection according to drug response, strategies consideration for overcoming drug resistance and the management of adverse events in long-term survival. These opinions would provide critical insights to improve HER2-low breast cancer treatment and offer valuable suggestions for clinical practice.

This case highlights the potential antitumor activity of apatinib in breast cancer patients with presenting with PLC. While further studies are necessary, this therapeutic approach could represent a viable option for managing breast cancer in the context of a visceral crisis. The case also emphasizes the importance of individualized treatment strategies and further research to substantiate these promising findings.

Mutational hotspots are a recurrent feature in both genes which, due to positive selection during tumorigenesis, can be potentially exploited by targeted treatments, as has been demonstrated by the US Food and Drug Administration (FDA)-approved PI3K inhibitor alpelisib in advanced hormone-receptor positive (HR+) breast cancer... The AGENA ClearSEEK PIK3CA and TP53 Panels combine low hands-on time requirements with accurate data assessment, and provide a reliable tool for clinical trial evaluation of known actionable PIK3CA mutations and response to PI3K inhibitors in breast cancer, as well as for investigating the oncogenic activities of TP53 hotspot mutations and patient selection e.g., for cell cycle targeting therapies.

P1, N=572, Recruiting, Seagen Inc. | N=430 --> 572 | Trial completion date: Jan 2027 --> Nov 2027 | Trial primary completion date: Jun 2025 --> Nov 2027

P=N/A, N=35, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting | Trial primary completion date: Feb 2025 --> Nov 2024

P2, N=60, Recruiting, The First Affiliated Hospital of Xi'an Jiaotong University; The First Affiliated Hospital of Xi'an Jiaotong University

P2, N=180, Recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=99, Active, not recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Recruiting --> Active, not recruiting | N=170 --> 99 | Trial completion date: Jun 2026 --> Apr 2028 | Trial primary completion date: Jan 2024 --> Apr 2025

P2, N=52, Completed, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori | Unknown status --> Completed | N=150 --> 52

NOLUS positivity was observed in 20.43% of patients aged 22-50, compared to 8.93% in those over 50, though this difference was not statistically significant. NOLUS exhibits potential in predicting pCR in HR+/HER2- breast cancer, serving as a cost-effective substitute for genomic tests.

For the treatment of breast cancer, there are three ADCs approved for breast cancer treatment: Trastuzumab emtansine (T-DM1), Trastuzumab Deruxtecan (T-Dxd) targeting HER-2, and Sacituzumab Govitecan (SG) targeting Trop-2. This review summarizes the efficacy and adverse effects of ADC therapies that have completed or are currently undergoing phase I-III clinical trials. Additionally, it analyzes potential combination strategies to overcome ADC resistance, aiming to provide clinicians with a comprehensive clinical guide to the use of ADCs in breast cancer treatment.

P1, N=26, Active, not recruiting, University of Michigan Rogel Cancer Center | Recruiting --> Active, not recruiting

P=N/A, N=200, Active, not recruiting, University College Cork | Trial completion date: Jun 2024 --> Dec 2024

These mechanisms collectively hinder tumor growth, immune evasion, and metastatic spread. By synthesizing recent findings and analyzing the impact of celecoxib on these pathways, this paper seeks to delineate the integrated approaches necessary for managing metastatic breast cancer effectively.

BCL-2 expression in IBC; NST has different prognostic effects depending on the molecular subtype of the cancer. In cancers with a HER2-enriched phenotype, BCL-2 expression was a marker of poor prognosis, while in cancers with a hormone receptor-positive phenotype, BCL-2 expression had a better prognostic impact.

P2, N=140, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Trial primary completion date: Dec 2023 --> Dec 2025

Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

P2, N=66, Recruiting, Henan Cancer Hospital | Trial primary completion date: May 2024 --> Dec 2024

P2, N=15, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

The entire study population experienced long-term survival, with median OS well over five years. IACT compared to CDCT did not improve outcome in patients with OMBC harboring study-defined HRD. The optimal therapy for patients with OMBC requires further study.

P3; In conclusion, although the number of randomized patients is small, patients with small, genomic high-risk breast cancer did not seem to derive benefit from chemotherapy. Endocrine therapy was associated with improved outcomes even in genomic low-risk breast cancers.

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High ENO1 expression was also associated with relapse-free, distant metastasis-free and overall survival, irrespectively of treatment and was mainly related to basal subtype. ENO1 overexpression recruits a range of signalling pathways during disease progression conferring a worse prognosis and can be potentially used as a biomarker of disease progression and therapeutic target, particularly in triple-negative and in ductal invasive carcinoma.

Furthermore, we derived a recurrence predictive index capable of predicting late recurrence, specifically in luminal subtypes, which plays a crucial role in guiding decisions on treatment durations for YBC patients. These findings improve the stratification and clinical implications for patients with YBC by contributing to the optimal adjuvant treatment and duration for favorable clinical outcomes.

Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further development of camizestrant for the treatment of oestrogen receptor-positive, HER2-negative breast cancer.

Furthermore, the side effects were manageable and no dose reductions were necessary during treatment. These findings suggest that the combination of CDK4/6i and ET in the treatment of HR+/HER2-advanced breast cancer cannot be underestimated.

Among patients with high molecular-risk HR+/HER2- EBC, the MP-High2, BP-Basal-type, and ImPrint positive signatures identified a partially overlapping subset of patients who were more likely to achieve pCR in response to neoadjuvant chemotherapy +/- targeted agents or immunotherapy compared to patients with MP-High1, BP-Luminal-type, and ImPrint negative disease. I-SPY2.2 is incorporating the use of these biomarkers to molecularly define specific patient populations and optimize treatment selection.

In patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer, inavolisib plus palbociclib-fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib-fulvestrant, with a greater incidence of toxic effects. The percentage of patients who discontinued any trial agent because of adverse events was low. (Funded by F. Hoffmann-La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.).

Distant metastases are rare in low-risk EBC. All in all, staging diagnostics should not be routinely employed in this patient population. Only patients with high Ki-67 developed distant metastases. In these cases, staging diagnostics may be discussed with the patient.