HR negative

HER2 expression levels (low/ultralow/null) stratify prognosis in HER2-negative eBC. The dynamic evolution of HER2 status following NAC and its prognostic utility highlights the importance of reassessing HER2 status in residual disease in HER2-negative eBC.

We report a 60-year-old woman with HER2-positive, hormone receptor-negative breast cancer who achieved pCR after neoadjuvant docetaxel combined with trastuzumab and pertuzumab, followed by 12 months of maintenance trastuzumab and pertuzumab. Emerging CNS-active therapies, including small-molecule tyrosine kinase inhibitors (TKIs) such as tucatinib and next-generation antibody-drug conjugates (ADCs) like trastuzumab deruxtecan, have shown promising intracranial activity. In addition, advanced strategies such as intensified MRI surveillance, radiomics, liquid biopsy, focused ultrasound-mediated BBB disruption, nanoparticle delivery systems, and radionuclide therapy offer potential avenues for early identification and prevention of cerebral metastases.

Adjuvant chemotherapy may optimize survival in select patients with T1b-T2N0M0 MBC, though prospective validation is warranted.

Ki67 appears to be an important prognostic biomarker in HR+ breast cancer across both HER2-low and HER2-positive subgroups. Dual stratification by HER2 and Ki67 status may improve risk assessment and help identify high-risk subgroups who could benefit from treatment approaches beyond endocrine therapy alone. These findings warrant confirmation in prospective studies.

P2, N=36, Recruiting, Laura Huppert, MD, BA | Not yet recruiting --> Recruiting

And small-tumor breast cancer patients do not usually benefit from AC. AC may not be recommended for certain subgroups, such as patients with pT1mi/a-bN0-1 HR+HER2- or pT1mi/a-bN0 HR-HER2-/HR+HER2+ can be exempted from chemotherapy.

The patient underwent a modified radical mastectomy followed by adjuvant chemotherapy and trastuzumab...This case highlights the diagnostic challenge of PCD, particularly when neurological manifestations precede tumor detection, and suggests that HER2-positive breast cancer may also be associated with anti-Yo antibodies. Early recognition of this syndrome and systematic malignancy screening are essential to improve patient outcomes.

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

Whole-genome sequencing of tumor samples carrying these germline risk variants revealed that they harbored mutational signatures indicative of a deficiency of homologous recombination. These findings suggest that hereditary POLH p.K589T and RAD51 p.M1fs are candidate variants associated with an increased risk of hormone receptor-negative breast cancer.

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.

Exploratory subgroup analysis further elucidated that OW/OB patients, particularly those aged > 50 years, postmenopausal, with lymph node involvement, hormone receptor negativity, or HER2 3 + status, exhibited substantially compromised pCR rates. Collectively, these findings substantiate the potential of BMI as a robust predictive biomarker for neoadjuvant therapy response in Chinese HER2-positive breast cancer patients.

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.