ER positive + HER-2 negative

Obesity was associated with lower ORR with letrozole alone, whereas this association was not observed in patients treated with taselisib.

P2, N=240, Active, not recruiting, AstraZeneca | Trial completion date: Mar 2026 --> Jun 2027

Overall concordance between Ki-67-based proliferation categories and RS-based genomic risk was 56.2%, with discordant cases in both directions. Ki-67 shows a modest association with Oncotype DX RS, but substantial discordance indicates Ki-67 should not substitute genomic testing in HR-positive/HER2-negative early breast cancer.

P2, N=119, Recruiting, Università Vita-Salute San Raffaele | Not yet recruiting --> Recruiting | Phase classification: PN/A --> P2 | N=221 --> 119 | Trial completion date: Nov 2028 --> Dec 2029 | Trial primary completion date: May 2027 --> Jun 2029

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