HER2 Negative Breast Cancer

P2, N=31, Active, not recruiting, Xijing Hospital | Recruiting --> Active, not recruiting | Trial completion date: Jul 2025 --> Jul 2028

P2, N=102, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Not yet recruiting --> Recruiting

Patients were divided into three groups: Group A (n=69, palbociclib 125 mg orally, 3 weeks on/1 week off, plus fulvestrant), Group B (n=72, ribociclib 600 mg orally, 3 weeks on/1 week off, plus fulvestrant), Group C (n=99, abemaciclib 150 mg orally, twice daily, plus fulvestrant). However, neither drug exhibits comprehensive superiority across all endpoints. Therefore, clinical treatment decisions should take consideration of multiple factors based on individualized medicine protocol.

Unlike the canonical activation of PAR1 by thrombin, which enhances cell proliferation via mechanistic target of rapamycin (mTOR) signaling, HAP-induced noncanonical activation downregulates mTOR activation and triggers autophagy in both estrogen receptor positive/ progesterone receptor positive/ HER2 negative (ER+/PR+/HER2-) and triple negative (ER-/PR-/HER2-) breast cancer cells...Importantly, the lack of PAR1 expression in normal, healthy breast epithelial cells facilitates the peptide to selectively target breast cancer cells with relatively high PAR1 expression, highlighting its potential as a therapeutic agent against low-grade malignant breast tumor. These findings provide valuable insights into autophagy activation by a synthetic peptide that targets breast cancer cells with high PAR1 expression and for the first time shows peptide mediated targeted therapy of low-grade malignant breast tumor.

In principle, the most effective and tolerable drugs should be used first with the goals of delaying chemotherapy and offering patients the best quality and duration of life. This review aims to explain the evolving treatment landscape for HR+HER2- advanced breast cancer and provides the scientific background for developing future treatment algorithms driven by preclinical and clinical results.

P1, N=33, Completed, BeOne Medicines | Active, not recruiting --> Completed | Trial completion date: Oct 2026 --> Apr 2026

P2, N=170, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Not yet recruiting --> Recruiting

In BCs with alterations in the AKT/PIK3CA pathway, capivasertib, alpelisib, and inavolisib have recently improved progression-free survival (PFS). Inavolisib (GC0077) differs from the other drugs targeting this pathway by its high potency and tolerability when combined with endocrine therapy, mostly with fulvestrant, and a CDK4/6 inhibitor. Its recent use in the first-line combined treatment for advanced HR+/HER2-negative BC has shown a PFS benefit compared to placebo in the INAVO120 trial, suggesting its role as a valid treatment option in PIK3CA-mutated patients. Further studies are warranted to confirm these results in terms of prolonging efficacy and maintaining durable responses - with a manageable safety profile - in clinical practice.

Tri-APBI as delivered with EBRT or HDR in this trial was feasible and well-tolerated, with low IBTR rates at 4 years and minimal impact on patient-reported quality of life, qualitative, and quantitative cosmesis. Further follow-up is needed to evaluate long-term oncologic efficacy.

P2, N=40, Completed, Beijing Wehand-Bio Pharmaceutical Co., Ltd | Phase classification: P1 --> P2

P=N/A, N=68, Active, not recruiting, Mayo Clinic | Trial completion date: Mar 2026 --> Mar 2028 | Trial primary completion date: Mar 2026 --> Mar 2028

This case represents a rare report of surgical resection for breast cancer liver metastasis after CDK4/6 inhibitor-based therapy. It suggests that local treatment may be effective even in cases with suspected endocrine-resistant disease and provides practical insight into patient selection and treatment strategies, as the case fulfilled previously reported criteria for local therapy.