fulvestrant

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.

In therapy-sensitive wild-type ER cells with low basal PML1 levels and PI3K/MAPK activity, fulvestrant's ER-suppressive effects overcome drug-induced elevated PML1 and PI3K/MAPK activity, thereby maintaining therapeutic efficacy...Notably, reducing PML1 levels through knockdown or arsenic trioxide (ATO), an FDA-approved PML1 degrader, disrupts this resistance circuit and restores endocrine sensitivity. Treatment of ATO resensitizes ER Y537S-bearing resistant tumors to endocrine therapy in xenograft models. These findings establish PML1 as a central hub of resistance, linking ER signaling to the activation of the PI3K/MAPK survival pathway.

P1, N=48, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting

P2, N=60, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Jun 2026 --> Dec 2026

P1, N=48, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

Mechanistically, the BRD4 PROTAC enhances fulvestrant sensitivity by down-regulation of GREB1 expression. Targeting BRD4 with PROTAC degraders represents a promising therapeutic strategy in breast cancer by suppressing GREB1 expression and enhancing the efficacy of fulvestrant.

P2, N=25, Not yet recruiting, MedSIR

P2, N=160, Not yet recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Patients in the high‑risk group showed improved responses to lapatinib, BI‑2536, OSI‑027, and SB505124, whereas those in the low‑risk subgroup had better sensitivity to axitinib, epirubicin, fulvestrant, and olaparib. Additionally, CD24 overexpression in BC cell lines promoted proliferation and migration, and inhibited apoptosis. These findings contribute to personalized treatment strategies and help elucidate the tumor microenvironment characteristics of BC patients.

P1, N=103, Active, not recruiting, BeiGene | Recruiting --> Active, not recruiting | N=258 --> 103 | Trial completion date: Jul 2028 --> Aug 2026 | Trial primary completion date: Apr 2028 --> Aug 2026

A 59-year-old woman with stage IIIA HR+/HER2- breast cancer underwent modified radical mastectomy in 2016, followed by adjuvant AC-P (doxorubicin hydrochloride 70 mg, cyclophosphamide 800 mg, and paclitaxel liposomes 180 mg) chemotherapy, radiotherapy, and letrozole maintenance...Since palbociclib was not yet covered by insurance, she received an initial chidamide + exemestane therapy, which proved ineffective. Using second-line palbociclib combined with fulvestrant and zoledronic acid therapy, disease stabilization was achieved for up to 12 months...As of September 2023, the patient has remained progression-free for >20 months and experienced only manageable grade 2 diarrhea. This case suggests that sequential CDK4/6 inhibition could help achieve >20 months of progression-free disease control in a patient with bone-only HR+/HER2- MBC after clinical progression during prior palbociclib-based therapy and underscored the need for biomarker-guided strategies in this distinct population.