HER-2 positive + HER-2 overexpression

Our patient presented with a visceral crisis denoted by impending liver failure, prompting the urgent initiation of first-line systemic therapy with fluorouracil, leucovorin, oxaliplatin and trastuzumab. This resulted in rapid clinical improvement, normalisation of liver function tests and tumour markers, and radiographic response with approximately 50% reduction in hepatic metastatic disease burden. This case underscores the aggressive behaviour and rarity of HER2-positive, AFP-producing gastric cancer, highlighting the critical need for prompt diagnosis and initiation of systemic therapy.

This multicenter retrospective study included 290 female patients diagnosed with HER2-positive early or locally advanced breast cancer treated with neoadjuvant trastuzumab and pertuzumab-based regimens (anthracycline-based [AC-THP] or non-anthracycline [TCHP]) across six centers. pCR remains the strongest surrogate for survival, neutralizing initial risk factors. These findings support using quantitative biomarker thresholds for personalization and reinforce the efficacy of non-anthracycline regimens.

Although the sample size is small, these findings support the clinical benefit of zanidatamab treatment for HER2-positive SGC.

P1/2, N=270, Completed, Dragonfly Therapeutics | Recruiting --> Completed | Trial completion date: Dec 2026 --> Dec 2025 | Trial primary completion date: Oct 2026 --> Dec 2025

These cases suggest that systemic HER2-targeted therapy can serve as an effective neoadjuvant approach for locally advanced HER2-positive SGCs. Conversion surgery following Tmab and DTX treatment may offer a curative option in selected patients initially deemed inoperable.

P2, N=197, Recruiting, Gruppo Oncologico del Nord-Ovest | N=140 --> 197

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center | Trial primary completion date: Jun 2026 --> Jul 2027

She received first-line chemotherapy with trastuzumab, pertuzumab, and docetaxel, followed by maintenance anti-HER2 therapy and surgery for local disease control. This case may represent an exceptional response to T-DM1 and highlights the potential for durable complete remission in selected patients with HER2-positive metastatic breast cancer. Further investigation is warranted to identify predictive factors for exceptional responses and to determine optimal treatment duration.

Secondary endpoints include duration of response, progression-free survival, disease control, occurrence of treatment-emergent adverse events, and health-related quality of life. Recruitment is ongoing in 13 countries globally.Clinical trial registration http://www.clinicaltrials.gov identifier is NCT06581432.

Notably, RC48 retained strong activity in BT474-derived sublines resistant to T-DM1, lapatinib, or neratinib, inducing cell cycle arrest, apoptosis, and caspase activation in all resistant models. Together, these findings identify disitamab vedotin as a potent next-generation HER2-targeting ADC with the unique capacity to overcome acquired resistance to HER2-directed therapies. RC48 represents a promising therapeutic strategy for patients with refractory HER2-positive breast cancer and warrants further clinical investigation.

Peripheral blood ALC levels are negatively correlated with HER2 expression in breast cancer. Given its accessibility and cost-effectiveness, ALC may serve as a complementary systemic immune indicator for contextual assessment of HER2-related immune characteristics and immune heterogeneity at the population level.

P=N/A, N=10, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2025 --> Sep 2026