HER-2 negative + ER positive

P4, N=75, Recruiting, Hebei Medical University Fourth Hospital | Trial completion date: Dec 2025 --> Dec 2028 | Trial primary completion date: Oct 2024 --> Oct 2026

P2, N=60, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

ERpHER2n-Basal breast cancer represents a clinically high-risk subgroup whose molecular resemblance to TNBC highlights potential therapeutic opportunities, particularly for immunotherapy and DNA repair-targeting treatments.

These findings suggest that the anti-breast cancer effect of DOT1L inhibition is mediated by multiple mechanisms, including activation of innate immune signaling.

ER-low/HER2-negative tumours had a high rate of pCR after the KEYNOTE-522 regimen. Our results suggest that patients with ER-low HER2-negative BC should be treated as ER-null/HER2-negative BC in the neoadjuvant setting to maximise pCR.

P3, N=1560, Active, not recruiting, Fudan University | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Jul 2027 | Trial primary completion date: Jul 2021 --> Jul 2026

Endocrine resistance in luminal breast cancer is characterized by elevated immune signatures, increased proliferation, and specific genomic alterations. The integration of clinical information, gene expression patterns, and genetic data enhances patient stratification and potentially informs treatment decisions. These findings support the use of integrative analyses to guide personalized endocrine therapy and improve outcomes.

TRIM37 expression is associated with increased cell proliferation, regardless of subtype; however, it is strongly associated with reduced immune activity, worse response to chemotherapy, and poor prognosis in ER-positive/HER2-negative BC, whereas it was associated with better response to chemotherapy and no relationship with survival in TNBC. Our results provide critical insights into the clinical application of TRIM37-targeted therapies.

P3, N=1017, Completed, UNICANCER | Active, not recruiting --> Completed

ER-low/HER2-negative breast cancers demonstrate BRCA1/2 mutation prevalence and features comparable to TNBC. Applying testing criteria based solely on ER expression may underdiagnose mutation carriers. These findings support expanding BRCA1/2 testing eligibility to include ER-low/HER2-negative tumors to ensure timely identification and access to targeted therapies.

Meanwhile, postmenopausal patients in the PR-zero (219 patients) and PR-low (167 patients) groups had similar prognosis, both significantly worse than the PR-high group (1,151 patients). Varying cutoff values of PR expression according to menopausal status could help determine more personalized treatment strategies.