HER-2 negative + HR negative

Five-profile classification provides a more accurate idea about the rate of potential change in treating BC in the metastatic setting.

With the approval of trastuzumab deruxtecan for the treatment of unresectable/metastatic HER2-low breast cancer, human epidermal growth factor receptor 2 (HER2)-low has emerged as a clinically actionable biomarker...Patients with discordant HER2 status had better responses to platinum-based chemotherapy. Therefore, for patients with HER2-0 primary lesions, re-evaluation of HER2 status in metastatic lesions through biopsy may offer new treatment opportunities.

Hormonal or endocrine therapy includes selective estrogen receptor modulators (SERMs) such as raloxifene, tamoxifen and toremifene, selective estrogen-receptor degraders (SERDs) including elacestrant and fulvestrant, and aromatase inhibitors such as anastrozole, letrozole, and exemestane...These agents include taxanes (docetaxel, nab-paclitaxel, and paclitaxel), anthracyclines (doxorubicin, epirubicin), anti-metabolites (capecitabine, gemcitabine, fluorouracil, methotrexate), alkylating agents (carboplatin, cisplatin, and cyclophosphamide), and drugs that target microtubules (eribulin, ixabepilone, ado-trastuzumab emtansine). Patients with ER-positive tumors are treated with 5-10 years of endocrine therapy and chemotherapy. For patients with metastatic breast cancer, standard first-line and follow-up therapy options include targeted approaches such as CDK4/6 inhibitors, PI3K inhibitors, PARP inhibitors, and anti-PDL1 immunotherapy, depending on the tumor type and molecular profile.

In both hormone receptor (HR)-positive (Log rank test, P=0.052) and HR-negative (Log rank test, P=0.125) subgroups, HER2 2+/FISH-negativity showed a marginally significant adverse influence on DFS. In older patients with HER2-negative/high-risk breast cancer undergoing standard adjuvant chemotherapy, our findings suggest that HER2 2+/FISH-negativity has an independent negative impact on prognosis.

P2, N=180, Recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=86, Completed, UNICANCER | Active, not recruiting --> Completed

P1/2, N=116, Recruiting, Cantargia AB | Trial primary completion date: Aug 2026 --> Jun 2025

With respect to the financial analysis, and taking into account the costs in both groups, the savings are marginal. Although more data are still required, in this study, the results suggest that Oncotype Dx should be indicated in N1 and only in N0 patients with Predict less than 4 and tumor grade 1 and 2, optimizing resources and improving cost-effectiveness.

RSC4All accurately reproduces RSClin™ results to support treatment decisions for patients with N0 HR+/HER2- eBC. The incorporation of SD further enhanced the predictive accuracy of the ML tool, supporting the value of AI-driven data augmentation in oncology.

The binding energy range for these ligands against their respective targets was calculated to be between -15 and -5 kcal/mol. Finally, based on general and common rules in medicinal chemistry, we selected 2, 3, 3, and 8 new ligands with high priority for further studies in the EGFR+HER2, ER, NF-κB, and PR classes, respectively.

Our study indicates that HER2-low status had no impact on pCR or DFS.

P1/2; Trial primary completion date: Aug 2024 --> Aug 2026

This study reveals the high heterogeneity of HER2-positive breast cancer related to HR status in clinicopathological features, metastasis patterns, and outcomes. Large randomized controlled trials are warranted to optimize treatment strategies for the HER2-positive breast cancer population.

P2, N=252, Recruiting, Guangdong Provincial People's Hospital | Initiation date: Jan 2024 --> Sep 2024

P1/2, N=29, Recruiting, Fujian Cancer Hospital | Not yet recruiting --> Recruiting | N=20 --> 29 | Trial completion date: Dec 2023 --> Jun 2025 | Trial primary completion date: Oct 2023 --> Dec 2024

These results suggest there are both subtype-specific and subtype-independent mechanisms that contribute to disparities in breast cancer survival between Black and White women, which require multilevel interventions to address and achieve health equity.

P1/2, N=29, Recruiting, University of Florida | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Jun 2025

I-SPY2.2 uses a sequential multiple assignment randomization trial design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent(s) (block A), a taxane-based regimen tailored to the tumor subtype (block B) and doxorubicin-cyclophosphamide (block C). Dato-DXd was particularly active in the hormone receptor-negative/HER2-Immune-DNA repair deficiency- signature, warranting further investigation, and was safe in other subtypes in patients who followed the treatment strategy. ClinicalTrials.gov registration: NCT01042379 .

HER-2 zero to low conversion was associated with better DFS in patients who are HER-2 zero. These results provide a valuable reference for the potential application of anti-HER-2 ADC in an adjuvant setting for patients with residual disease after NAC.

Among females with LFS and BC, HER2-positive subtype was associated with younger age at diagnosis and a predominant HR-positivity. Favorable pCR rates were observed among those receiving neoadjuvant HER2-directed therapies, for both HR-positive and negative tumors. These data may inform the counseling and care of patients with LFS.

The analysis revealed that the six most effective neoadjuvant treatment regimens for HR+/HER2- breast cancer were: CT(A)+olaparib (82.5%), CT(A)+nivolumab (76.5%), Com (74.9%), CT (72.1%), Mono+eribulin (72.0%), and CT(A)+pembrolizumab (70.4%).Paired meta-analysis for pathological complete response (pCR) found no statistically significant distinction between treatment regimens that included both anthracycline and immunosuppressants and regimens that relied solely on anthracycline chemotherapy(OR:1.14, 95%ci 0.79-1.64, I2 = 71%, P=0.50). Although pCR is valuable in assessing the effect of neoadjuvant therapy in some cases, prognostic prediction and efficacy assessment in patients with HR+/HER2- breast cancer should be based on a combination of broader clinical and biological characteristics. PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024534539, CRD42024501740.

Over 90% of patients with clinically node-negative, microinvasive and T1a breast cancer remain pathologically node-negative following axillary staging. However, higher rates of nodal disease were found among Black patients, older patients, and patients with lobular cancer and significant comorbidities.