HER-2 expression

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.

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.

Collectively, these findings establish HER2‑low expression as a negative predictor of immunotherapy response, shaped by a less immunogenic tumor microenvironment. These results provide important insights into the distinct immunological features of HER2‑low triple‑negative breast cancer and warrant further mechanistic and clinical investigations.

Three ADCs are currently approved for previously treated gynaecological cancers: mirvetuximab soravtansine for folate receptor-α-positive ovarian cancer, trastuzumab deruxtecan for solid tumours expressing HER2 (defined as a staining intensity on immunohistochemistry of 3+) and tisotumab vedotin for cervical cancer (independent of tissue factor expression). Moreover, rational combinations could reinforce and extend the clinical potential of these agents, as has already been demonstrated with the addition of ADCs to immune checkpoint inhibitors in an effort to amplify antitumour immunity and prolong the durability of clinical responses. In this Review, we provide an overview of the current landscape of ADCs in gynaecological malignancies, highlighting key advances and future opportunities.

ADCs against TROP2 (Sacituzumab govitecan) or HER2 (T-DXd) have demonstrated efficacy in metastatic breast cancer, yet paradoxically, outside of HER2-amplified breast cancers, expression levels of these breast cancer-enriched epitopes in tumor biopsies have not been strongly correlated with clinical response. Thus, while CTC burden is correlated with response to these ADCs, the level of TROP2 or HER2 expression is poorly predictive. These findings point to sensitivity to the drug payload as a potential driver of clinical response to currently approved ADCs in breast cancer.

P3, N=412, Active, not recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial primary completion date: Jun 2026 --> Jan 2027

DWI and ADC represent reliable methods for distinguishing between benign and malignant breast lesions. The observed association between ADCratio values and HER2 expression suggests that this parameter may be useful in identifying breast cancer patients with poor prognostic profiles.

hsa-miR-26b-5p and hsa-miR-186-5p demonstrate complementary roles in BC biology. hsa-miR-26b-5p is primarily associated with tumor aggressiveness and cancer progression, whereas hsa-miR-186-5p refl cts its molecular characteristics and response to chemotherapy. Their combined assessment in serum and tumor tissue represents a promising approach for improving prognostic stratifi ation and predicting treatment effi acy in BC patients.

Our findings suggest that NEAT1 and miR-506-3p exhibit opposite expression patterns in TNBC tissues and may serve as complementary tissue-based candidate diagnostic biomarkers. Their combined use showed improved discriminatory performance in this cohort; however, larger independent validation studies are required before a clinical diagnostic application can be proposed.

Complex relationships between ERBB2 alterations and HER2 IHC expression exist, including increased expression in non-ERBB2-amplified tumors with pathogenic mutations. Importantly, ERBB2/HER2 amplification and/or mutation rates as well as transcript and protein expression varied between cancers and within cancer types, emphasizing the need for individual assessment.

Notably, in human cell lines HER2∆16 expression is elevated upon acquired resistance to HER2-targeted therapy and can sensitize cells to the ER-antagonist tamoxifen. Overall, these findings offer valuable insights into the role of HER2∆16 in promoting luminal cell identity and estrogen receptor positivity in breast cancer, providing a useful platform to model HER2+/ER+ disease.

STARD10 promotes malignant progression of HER2+ breast cancer and lipid droplets accumulation by activating the cAMP/PKA/CREB1 pathway. These findings suggest that STARD10 and the cAMP/PKA/CREB1 signaling axis as potential therapeutic targets for the treatment and prevention of HER2+ breast cancer.