HER-2 negative + HR negative

P2, N=80, Not yet recruiting, Sun Yat-sen University

P1/2, N=980, Recruiting, BioNTech SE | N=550 --> 980 | Trial completion date: Feb 2030 --> Oct 2029 | Trial primary completion date: May 2028 --> Feb 2028

In conclusion, modern axillary management in HR-positive, HER2-negative breast cancer involves navigating the intersection between de-escalated surgery and risk-adapted systemic therapy. Future strategies should prioritize individualized care, incorporating tumor biology, imaging findings, and patient preferences, with multidisciplinary collaboration playing a central role in optimizing outcomes.

P1/2, N=29, Suspended, University of Florida | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

Young Black women were more likely than White women to elect the less-invasive surgery (lumpectomy). Private insurance was associated with better OS and RFS.

P3, N=474, Completed, Istituto Oncologico Veneto IRCCS | Active, not recruiting --> Completed

We reveal the potential of nanoDSF and AI applied to plasma samples to discriminate between BC patients and HC. If these results are confirmed, such approach could represent a minimally-invasive, low risk, quick and low-cost technique, which could help to improve the screening of BC.

With adequate follow-up, distant disease-free survival is a robust surrogate endpoint for predicting final overall survival outcomes in neoadjuvant RCTs for early breast cancer in most contexts. However, the distant disease-free survival surrogacy appears to be weak for the hormone receptor-positive and HER2-negative and for the hormone receptor-positive and HER2-positive molecular subtypes. These latter findings warrant further investigation in more recent RCTs enrolling higher-risk patient populations.

In conclusion, HER2-ultralow status is not associated with distinct clinicopathologic or genomic characteristics. HER2-IHC 0 (MS-) and ultralow statuses often coexist within the same patient.

Baseline characteristics indicative of reduced hormonal signaling and non-luminal tumor biology assessed more precisely using mRNA profiling can guide optimal tailoring of NACT for patients with high-risk HR+/HER2-tumors. Baseline molecular biology did not predict surgical outcomes following NACT.

Except for the worst OS in the constant HER2-zero, hormone receptor-negative subgroup, no significant differences were observed in the DFS and OS with respect to the changes of HER2-zero and HER2-low groups. The prognostic significance of HER2-zero and HER2-low changes after NAC requires further exploration through prospective studies.

Despite lower ORRs in patients with BRCA1 mutations or MYC amplifications, the differences were not statistically significant. This study confirms the clinical efficacy and manageable safety profile of T-DXd in this population, identifying high-risk subgroups and potential resistance biomarkers to inform treatment decisions.