HER2 Negative Breast Cancer

P3, N=400, Recruiting, Pfizer

P2, N=80, Recruiting, Hoffmann-La Roche | N=44 --> 80 | Trial completion date: Dec 2030 --> Feb 2030

P2, N=40, Recruiting, National Cancer Centre, Singapore | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Dec 2025 --> Dec 2026

Patients with endocrine-sensitive disease at the time of BrM diagnosis had a longer brain-specific progression-free survival (7 mo versus 5 months, P = .004) and overall survival (24 months versus 5 mo, P  = .002) compared with those with endocrine resistance. Most patients with HR+/HER2- BrM have endocrine-resistant disease, with an unexpectedly high likelihood of developing LMD.

Prompt recognition, intensive management, and drug discontinuation are critical. This is one of the first case reports to describe sustained euglycemia following severe and refractory hyperglycemia due to capivasertib therapy.

The pseudo-SHAP method provides a scalable, interpretable auditing framework for detecting shortcut learning in resource-constrained environments. Its application could enhance transparency and equity in AI models for precision oncology.

5-Fluorouracil (5-FU) and its prodrugs are widely used drugs for chemotherapy in various cancers. In conclusion, our study reveals that everolimus sensitizes breast cancer to fluoropyrimidines by destabilizing TYMS through modulation of its O-GlcNAcylation. These findings support a promising combination strategy to improve the therapeutic efficacy of 5-FU and capecitabine in breast cancer.

Optimized staging and risk assessment in HR+/HER2- EBC is critical to identify high-risk patients eligible for CDK4/6 inhibitors. Implementing these recommendations may improve patient outcomes in the adjuvant setting.

P2, N=28, Completed, Asan Medical Center | Recruiting --> Completed

By contrast, sacituzumab govitecan is a TROP-2-targeted ADC conjugated through a hydrolysable CL2A linker to SN-38, the active metabolite of irinotecan. Clinically, trastuzumab deruxtecan has shown substantial efficacy in both HER2-positive and HER2-low breast cancer, whereas sacituzumab govitecan has demonstrated efficacy across triple-negative and hormone receptor-positive/HER2-negative breast cancers. Collectively, these agents highlight how variations in target antigen, linker chemistry, and payload potency impact ADC activity, therapeutic index, and potential strategies for sequential treatment in advanced breast cancer.

This phase II trial evaluated the efficacy and safety of combining niraparib with the PD-1 inhibitor HX008 in patients with metastatic breast cancer who had germline DNA damage response (DDR) mutations. Somatic TP53 mutations significantly correlated with shorter PFS, while ASXL1 mutations correlated with longer PFS. This chemotherapy-free regimen demonstrates promising efficacy and a tolerable safety profile in patients with metastatic breast cancer and germline DDR mutations, providing a novel therapeutic option for this patient population, even those with brain metastases.

The most common regimens included capecitabine and everolimus plus exemestane. Multivariable analysis showed that younger age, prior fulvestrant use, and shorter CDK4/6i duration were associated with CHT choice...Treatment decisions are influenced by clinical history and patient characteristics. These findings underscore the need for personalized approaches and molecular profiling to guide post-CDK4/6i therapy in HR-positive/HER2-negative MBC.