HER-2 negative + HR negative

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.

P2, N=38, Not yet recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P2, N=125, Not yet recruiting, Shengjing Hospital of China Medical University; Shengjing Hospital of China Medical University

Statistically significant differences in unadjusted overall survival distributions were observed among breast cancer molecular subtypes. HR-positive breast cancers demonstrated better overall survival than HR-negative cancers, while no statistically significant difference in unadjusted survival was observed between HER2-positive and HER2-negative groups.

In patients with HR-HER2 + EBC, the neoadjuvant therapy with trastuzumab, pyrotinib and dalpiciclib has promising activity and manageable toxicity. Further investigation is needed.

While certain subgroups, like HR-positive or high Ki-67 cases, showed better DFS in the HER2-low group, overall, there were no significant differences in DFS or OS. These results suggest HER2-low and HER2-zero breast cancers share largely similar features and outcomes; however, in certain subgroups, HER2-low tumors were associated with significantly better DFS, possibly reflecting differences in tumor biology. Further research is essential to clarify the biological role of HER2-low expression.

P2, N=46, Active, not recruiting, Virginia Commonwealth University | Trial completion date: Feb 2025 --> Mar 2026