HER2 Positive Breast Cancer

P1/2, N=1132, Recruiting, Hoffmann-La Roche | N=792 --> 1132

P2, N=43, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

In a multivariate regression analysis the cumulative dose of anthracycline (OR = 1.01, 95% CI: 1.00-1.01, p = 0.002) and LVEF at baseline (OR = 0.83, 95% CI: 0.70-0.99, p = 0.0344) were independent predictors of a cardiotoxic effect. Trastuzumab-related cardiotoxicity resulting in early treatment discontinuation negatively influences DFS, but does not seem to influence OS.

HER2-low status was associated with worse OS in breast cancer patients with certain negative prognostic factors compared with HER2-zero status. Additionally, HER2-low1+ and HER2-low2+/ISH(-) subgroups predominantly exhibited HR+ status.

We developed and validated a well-calibrated nomogram for predicting DFS in patients with HR+/HER- breast cancer. This nomogram uniquely integrates MHR with clinicopathological factors to predict prognosis in HR+/HER2- breast cancer and can facilitate individualized therapeutic planning.

Antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) offer new and potent options for curing for curing hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-low advanced breast cancer; however, comparisons in terms of their relative effectiveness and safety concerns are lacking. Compared with other ADC drugs, T-DXd showed relatively better treatment characteristics, better PFS benefit, and relatively low incidence of serious AEs (SAEs). Combined with RCTs and real-world data, T-DXd has potential advantages in this population.

Utidelone plus capecitabine has brought therapeutic and survival benefits in the second-line treatment of patients with advanced breast cancer (ABC). Utidelone demonstrates favorable efficacy and safety in patients with refractory ABC, particularly in HR+/HER2- patients. The combination of utidelone with anti-angiogenic therapy shows promising intracranial anti-tumor activity and is expected to be a preferred option for ABC in subsequent lines of treatment.

The nomogram based on HER2 status shows promising preliminary predictive performance in predicting pCR. Given the lack of external validation and single‑center design, this model remains exploratory and hypothesis‑generating.

SPDEF is specifically downregulated in TNBC, and its high expression is associated with earlier tumor stage and favorable clinical outcomes. SPDEF suppresses TNBC cell proliferation, migration, and invasion while promoting apoptosis through modulation of apoptosis-related protein expression, highlighting its potential as a prognostic biomarker and therapeutic target for TNBC.

Outcomes were excellent regardless of chemotherapy or ET, suggesting limited incremental benefit from treatment intensification.

We recommend a tiered approach of CAB testing in patients with MF/MC BC, whereby, if the first tumor shows CAB-low risk, testing of additional tumor foci is recommended. This approach improves risk stratification and enables tailored adjuvant treatment planning, while minimizing the risk of undertreatment.

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