Hormone Receptor Positive Breast Cancer

P2, N=168, Not yet recruiting, Universitaire Ziekenhuizen KU Leuven

Culturally sensitive efforts are needed to promote awareness and increase breast cancer screening in distinct ethnic groups. The rapid recent increases in breast cancer incidence in Asian American, Native Hawaiian, and Pacific Islander women, especially early-onset disease, warrant urgent attention.

Younger patients with breast cancer exhibited a higher frequency of high-grade tumors, although no differences were observed in RFS and DRFS. However, locoregional recurrence was more common among younger patients, especially HR-positive/HER2-negative breast cancer.

Herein, we developed drug-conjugated Tam-NHC-gold(I) complexes that can target breast cancer cells by the binding of tamoxifen (Tam) to the G protein-coupled estrogen receptor (GPER) present on cell membranes...Moreover, 7b exhibited potent antiproliferative activity on both wild-type and mutant MCF-7Y537S in xenograft mouse models with low toxicity. This study verified that 7b may offer a new approach for the treatment of endocrine-resistant breast cancer.

This case highlights a rare but severe complication of ABE treatment. While CDK4/6 inhibitors are widely used as first-line agents in advanced breast cancer due to their high efficacy and generally favorable side-effect profile, clinicians should remain vigilant for NE, which requires prompt intervention.

P2, N=99, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Jun 2026 --> Dec 2026

P2, N=48, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2026 --> May 2027 | Trial primary completion date: Jun 2026 --> May 2027

HRD represents a reliable independent prognostic biomarker in HR+/HER2- breast cancer in this cohort, with an inverse association with TILs suggesting immune evasion. Its potential impact on prognosis and treatment requires further validation in prospective clinical trials.

In general, both AI and FUL combinations are effective alternatives, irrespective of the CDK4/6i treatment line, liver metastasis at first relapse, or endocrine sensitivity. Further studies are expected.

Trastuzumab + pertuzumab (TP) was the most commonly used regimen in both neoadjuvant and adjuvant settings. The dual HER2 blockade regimens that were widely adopted in China for HR+/HER2+ early breast cancer have demonstrated effectiveness in improving pCR in routine clinical practice; a longer follow‑up is required to validate survival outcomes. None.

Tucatinib-based combinations and trastuzumab deruxtecan have demonstrated substantial intracranial activity in prospective trials, shifting the treatment paradigm by supporting systemic therapy even in the presence of active brain metastases. A major limitation remains the underrepresentation of patients with brain metastases in clinical trials. This review summarizes current evidence on systemic therapies for BCBM across subtypes and highlights the need for CNS-inclusive trials and the development of effective CNS-active treatments.

The clinical deployment of ATP-competitive inhibitors-Palbociclib, Ribociclib, and Abemaciclib-has revolutionized the standard of care for hormone receptor-positive breast cancer. By recruiting the ubiquitin-proteasome system to catalytically degrade target proteins, CDK4/6-PROTACs eliminate both enzymatic activity and non-catalytic scaffolding functions, offering a mechanistically distinct strategy to overcome the structural limitations of traditional inhibitors. This review summarizes the progression from clinical inhibitors to strategies for overcoming resistance, offering insights into the future development of CDK4/6-targeted therapies.