ER positive + HER-2 negative

P1, N=61, Active, not recruiting, Institute of Cancer Research, United Kingdom | Recruiting --> Active, not recruiting | Trial completion date: Mar 2026 --> Dec 2026 | Trial primary completion date: Mar 2026 --> Dec 2026

The FROC model could help identify the low Ki67 expression (≤ 5%) and prevent unnecessary chemotherapy.

Short-course preoperative ET induces rapid and reproducible morphological and immunophenotypic changes in ER-positive, HER2-negative breast cancer. Ki67-defined response is associated with genomic risk and PR expression, whereas microenvironmental features appear to have limited predictive value.

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.