ER positive + HER-2 negative

Routine assessment of ESR1 mutations using liquid biopsy should be integrated into clinical practice to enable dynamic, molecularly guided treatment optimization. The expanding arsenal of ER-targeted therapies supports personalized sequencing strategies that move beyond rigid temporal cutoffs and improve outcomes in ET resistant disease.

A rise in mTF (molecular progression) precedes treatment discontinuation by a median of 5.8 months and outperforms mutation-based tracking, with resistance-associated alterations in ESR1 and RB1 frequently emerging at molecular progression. These findings support prospective evaluation of mTF-guided treatment strategies.

AR expression may have prognostic value in ER+/HER2- breast cancer, particularly for DFS and in selected patients with residual disease after neoadjuvant chemotherapy. Further prospective studies with longer follow-up are warranted.

TP53 mutation is associated with shorter CDK4/6i treatment duration, highlighting the importance of considering both genomic and age-related clinical context when interpreting treatment duration in ER-positive/HER2-negative breast cancer.

In contrast, RS testing appeared less influential in treatment decisions for patients with clearly defined low- or high-risk clinicopathologic profiles or favorable special histologic subtypes. Overall, current evidence indicates that RS cannot be reliably replaced by other indicators, while its clinical value varies by context, suggesting that a selective rather than uniform application of RS testing may be reasonable in some settings.

For ER+/HER2- early breast cancer, the utility of genomic assays such as Oncotype DX, PAM50, and MammaPrint is discussed, with a focus on chemotherapy selection and the role of CDK4/6 inhibitors, and the role of extended endocrine therapy and adjuvant zoledronic acid. In HER2-positive breast cancer, we examine neoadjuvant therapy with dual HER2 blockade (trastuzumab and pertuzumab), personalized regimens that minimize cardiotoxicity, and the potential of antibody-drug conjugates. For TNBC, the growing role of immunotherapy, dose-dense regimens, and adjuvant capecitabine is reviewed, with a focus on olaparib in BRCA-mutated cases. This review also addresses special populations, including BRCA mutation carriers and premenopausal women, and looks at future trends in systemic therapy, including novel agents, biomarker-driven approaches, and treatment de-escalation strategies.

P1, N=181, Active, not recruiting, Genentech, Inc. | Trial completion date: Jul 2026 --> Jul 2027 | Trial primary completion date: Jul 2026 --> Jul 2027

P2, N=1100, Active, not recruiting, SOLTI Breast Cancer Research Group | Recruiting --> Active, not recruiting

These findings demonstrate that baseline SUVmax is a strong and readily accessible prognostic biomarker in patients receiving CDK4/6i, helping to identify individuals at elevated risk of early disease progression. Prospective validation is warranted.

P3, N=3902, Recruiting, UNICANCER

IDC-LL demonstrates clinicopathologic and molecular features intermediate between IDC and ILC. Recognition of IDC-LL as a distinct morphologic category is warranted to optimize diagnosis and surgical management.