HR positive

In our cohort with 5-y survival data, BCT is a safe option for women aged 40 y and under who are diagnosed with breast cancer. Despite no survival benefit, young women with breast cancer in our cohort underwent mastectomy more often than lumpectomy. Importantly, most recurrences were distant metastases, suggesting that local therapy choice is less relevant to outcome.

Prognostic stage significantly influences survival among patients with low RS. RS < 11 alone should not automatically downstage patients to PPS IA; anatomic and other nongenomic factors remain important for prognosis.

Central determination of AR showed significant enrichment in HER2-low compared with HER2-0 mTNBC (mean: 33.7% vs. 21.4%, p = 0.038), whereas no significant immunological differences were observed. HER2-low/AR-positive patients trended towards longer overall survival, highlighting the potential relevance of these biomarkers.

P=N/A, N=88, Not yet recruiting, Addis Ababa University

P2, N=36, Not yet recruiting, Laura Huppert, MD, BA | Trial completion date: Mar 2029 --> Jun 2029 | Trial primary completion date: Mar 2029 --> Jun 2029

P1/2, N=230, Recruiting, Exscientia AI Ltd., a wholly owned subsidiary of Recursion Pharmaceuticals, Inc. | N=165 --> 230

NET is a viable alternative to NCT in HR+/HER2- patients. CDK4/6 + ET demonstrates superior tumor reduction and safety, potentially enabling postoperative therapy de-escalation. These findings support NET as a strategic option for optimizing outcomes while minimizing toxicity.

In ER-positive, HER2-positive breast cancer, negative or weak PR expression was associated with inferior DFS and DRFS compared to strong PR expression. These findings highlight the potential prognostic value of PR status in this group, underscoring its relevance in guiding treatment and follow-up strategies for more individualized patient care.

In this retrospective cohort of 280 HR+/HER2- patients, initial endocrine therapy was AI+OFS (n = 95), tamoxifen (TAM; n = 141), or TAM+OFS (n = 44)...In premenopausal women with HR+/HER2- breast cancer, AI+OFS was associated with an adverse lipid profile and a possible increase in carotid plaque compared with TAM-based regimens. Regimen-dependent associations between SHD and lipid profiles support individualized cardiovascular monitoring and cautious use of adjunctive SHD in this population.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i; palbociclib, ribociclib, abemaciclib, dalpiciclib) combined with endocrine therapy (ET) were a major advance in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) worldwide...However, clinical development of CDK4/6i in HER2+ MBC slowed, given the advent of highly effective tyrosine-kinase inhibitors (TKIs) (i.e., tucatinib) and antibody-drug conjugates (ADCs) (i.e., trastuzumab deruxtecan), which currently dominate the treatment armamentarium...Subsequently, the phase III PATINA trial (which included patients with 1L HR+HER2+ MBC, treated with palbociclib vs. placebo with maintenance ET+ H&lsqb;P]) noted a striking PFS improvement of >15 months in the palbociclib arm, renewing interest in CDK4/6i-based treatments for HR+HER2+ MBC. Herein, we review the development of CDK4/6i in HER2+ BC, discussing current challenges and potential future directions.

By integrating data from clinical trials, molecular analyses, and patent landscapes, this review illustrates how multimechanistic, biomarker-guided therapies supported by advanced drug-delivery technologies are redefining contemporary precision oncology in breast cancer. The emerging therapeutic paradigm underscores the convergence of targeted therapy, immunomodulation, synthetic lethality, and localized immune-activating approaches, charting a path toward further personalization of treatment in the years ahead.

P=N/A, N=12, Not yet recruiting, University of Vermont Medical Center