Exploring the clinical outcomes and safety profile of inetetamab treatment in metastatic breast cancer patients: A multicenter assessment of a Chinese-origin recombinant Anti-HER2 monoclonal antibody.

BACKGROUND: Inetetamab is a novel recombinant humanized anti-HER2 monoclonal antibody. This study aimed to evaluate the efficacy and safety of inetetamab and predictive factors for response in HER2-positive metastatic breast cancer (MBC) patients. METHODS: A cohort of HER2-positive MBC patients who received inetetamab-based therapy between June 2020 and August 2021 was evaluated. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Adverse events (AEs) were graded according to the National Cancer Institute Common Toxicity Criteria. RESULTS: A total of 141 patients were included in the final analysis. The median PFS of the entire cohort was 7.1 months. The median number of treatment lines administered was three. The ORR was 36.9 %, and the DCR was 80.9 %. The most frequently employed treatment strategy was inetetamab + chemotherapy (49/141, 34.8 %), followed by inetetamab + HER2-tyrosine kinase inhibitors (HER2-TKIs) + chemotherapy, inetetamab + pertuzumab + chemotherapy, inetetamab + endocrine treatment and inetetamab + HER2-TKIs. Cox multivariate analysis revealed that PFS was associated with liver metastasis (hazard ratio [HR] 2.112, 95 % confidence interval [CI] 1.334-3.343, p = 0.001), previous HER2-TKI treatment (HR 2.019, 95 % CI 1.133-3.597, p = 0.017) and estrogen receptor positivity (HR 0.587, 95 % CI 0.370-0.934, p = 0.024). The toxicity was tolerable, with neutropenia being the most common treatment-related grade 3/4 AE (14.9 %). CONCLUSION: Inetetamab demonstrates effectiveness with a manageable safety profile, offering a promising therapeutic option for HER2-positive breast cancer patients who have shown resistance to prior anti-HER2 treatments.

Significant response to the combination of pyrotinib and letrozole in a patient with metastatic HER2-positive and hormone receptor-positive breast cancer: a case report.

Breast cancer is the most commonly diagnosed malignant tumor and the leading cause of cancer-related death in women worldwide. Previous studies have demonstrated that patients with human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-positive metastatic breast cancer can benefit from HER2-targeted therapy. Pyrotinib, an irreversible tyrosine kinase inhibitor (TKI), has been demonstrated to be effective and safe in treating HER2-positive breast cancer patients. Letrozole is an aromatase inhibitor (AI) which has shown better clinical efficacy when combined with HER2 inhibitors in treating patients with HER2-positive and HR-positive breast cancer than has hormonal therapy alone. However, the effect of combination therapy with pyrotinib plus letrozole in HER2-positive/HR-positive metastatic breast cancer patients has not yet been investigated. In this case report, a 57-year-old female patient with HER2-positive/HR-positive breast cancer received modified radical mastectomy and experienced subsequent relapse and metastasis. She was diagnosed with relapsed right breast cancer, a right chest bone mass accompanied by bone destruction, and metastases in the chest wall and both lungs. She was then enrolled in a phase II clinical trial and was treated with pyrotinib plus letrozole, and achieved a durable clinical response. Our case shows that combination therapy with pyrotinib plus letrozole may provide significant clinical benefit for patients with HER2-positive/HR-positive metastatic breast cancer, with tolerable adverse events.

FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients.

BACKGROUND: The survival status of patients with breast cancer and brain metastasis (BCBM) receiving current treatments is poor. METHOD: We designed a real-world study to investigate using patients' clinical and genetic aberrations to forecast the prognoses of BCBM patients. We recruited 146 BCBM patients and analyzed their clinical features to evaluate the overall survival (OS). For genetic testing, 30 BCBM and 165 non-brain-metastatic (BM) metastatic breast cancer (MBC) patients from Hunan Cancer Hospital, and 86 BCBM and 1416 non-BM MBC patients from the Geneplus database who received circulating tumor DNA testing, were compared and analyzed. RESULTS: Ki67 >14% and >3 metastatic brain tumors were significant risk factors associated with poor OS, while chemotherapy and brain radiotherapy were beneficial factors for better OS. Compared with non-BM MBC patients, BCBM patients had more fibroblast growth factor receptor (FGFR) aberrations. The combination of FGFR, TP53 and FLT1 aberrations plus immunohistochemistry HER2-positive were associated with an increased risk of brain metastasis (AUC = 77.13%). FGFR aberration alone was not only a predictive factor (AUC = 67.90%), but also a significant risk factor for poor progression-free survival (Logrank p = 0.029). FGFR1 aberration was more frequent than other FGFR family genes in BCBM patients, and FGFR1 aberration was significantly higher in BCBM patients than non-BM MBC patients. Most FGFR1-amplified MBC patients progressed within 3 months of the late-line (>2 lines) treatment. CONCLUSION: A group of genetic events, including FGFR, TP53 and FLT1 genetic aberrations, and HER2-positivity, forecasted the occurrence of BM in breast cancers. FGFR genetic aberration alone predicted poor prognosis.

In Vivo Detection of CTC and CTC Plakoglobin Status Helps Predict Prognosis in Patients with Metastatic Breast Cancer.

This study aims to detect the prognostic value of circulating tumour cell (CTC) in patients with metastatic breast cancer. In this study, 38 patients with metastatic breast cancer were enrolled. The in vivo CellCollector® method was used to detect the number of CTC in patients. Single CTC and CTC clusters were counted, and the expression of plakoglobin was also analysed. At baseline, 73.7% (28/38) of the patients were positive for ≥ 1 CTC (range, 1-14 cells). No CTC-like events were observed in the control group. Among the CTC-positive patients, 21.4% (6/28) of patients had CTC clusters, and 42.9% (12/28) of patients had plakoglobin-positive CTC. After chemotherapy, 48.6% (17/35) of the patients were positive for ≥ 1 CTC (range, 1-3 cells), of which 3 patients had CTC clusters, and 35.3% (6/17) had plakoglobin-positive CTC. Additionally, we found that the number of CTC clusters in plakoglobin-positive patients was much greater than that in plakoglobin-negative patients, and the number of CTC was associated with the number of sites of metastases. We also found that patients with ≥ 3 CTC at baseline had shorter progression-free survival (PFS) and overall survival (OS), and pre-chemotherapy CTC detection was associated with PFS (P = 0.0001) and OS (P = 0.0091). CTC plakoglobin expression was associated with PFS (P = 0.02) but not OS (P = 0.22). CTC collected by the in vivo CellCollector method in Chinese patients with metastatic breast cancer have prognostic significance. CTC plakoglobin expression may be associated with CTC clusters, and more in-depth studies are needed.

Identifying Circulating Tumor DNA Mutation Profiles in Metastatic Breast Cancer Patients with Multiline Resistance.

PURPOSE: In cancer patients, tumor gene mutations contribute to drug resistance and treatment failure. In patients with metastatic breast cancer (MBC), these mutations increase after multiline treatment, thereby decreasing treatment efficiency. The aim of this study was to evaluate gene mutation patterns in MBC patients to predict drug resistance and disease progression. METHOD: A total of 68 MBC patients who had received multiline treatment were recruited. Circulating tumor DNA (ctDNA) mutations were evaluated and compared among hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) subgroups. RESULTS: The baseline gene mutation pattern (at the time of recruitment) varied among HR/HER2 subtypes. BRCA1 and MED12 were frequently mutated in triple negative breast cancer (TNBC) patients, PIK3CA and FAT1 mutations were frequent in HR+ patients, and PIK3CA and ERBB2 mutations were frequent in HER2+ patients. Gene mutation patterns also varied in patients who progressed within either 3 months or 3-6 months of chemotherapy treatment. For example, in HR+ patients who progressed within 3 months of treatment, the frequency of TERT mutations significantly increased. Other related mutations included FAT1 and NOTCH4. In HR+ patients who progressed within 3-6 months, PIK3CA, TP53, MLL3, ERBB2, NOTCH2, and ERS1 were the candidate mutations. This suggests that different mechanisms underlie disease progression at different times after treatment initiation. In the COX model, the ctDNA TP53 + PIK3CA gene mutation pattern successfully predicted progression within 6 months. CONCLUSION: ctDNA gene mutation profiles differed among HR/HER2 subtypes of MBC patients. By identifying mutations associated with treatment resistance, we hope to improve therapy selection for MBC patients who received multiline treatment.

Cytochrome P450 1A1 (CYP1A1) Gene Polymorphisms and Susceptibility to Breast Cancer: a Meta-Analysis in the Chinese Population.

BACKGROUND: Although various individual studies have evaluated the correlation between cytochrome P450 1A1 (CYP1A1) polymorphisms and breast cancer, the results remain inconclusive. To further evaluate the influence of CYP1A1 polymorphisms on breast cancer risk, we conducted a meta-analysis in the Chinese population. METHODS: Studies were identified using PubMed and Chinese databases through December 2015. Pooled odd ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strengths of these associations. RESULTS: This meta-analysis included 6 studies with 1837 breast cancer cases and 1970 controls. No significant association of CYP1A1 T3801C polymorphism and breast cancer was observed in the Chinese population (C vs. T: OR = 1.01, 95% CI = 0.74 - 1.37; CC vs. TT: OR = 1.08, 95% CI = 0.65 - 1.78; CC vs. TT + CT: OR = 1.02, 95% CI = 0.84 - 1.24; CC + CT vs. TT: OR = 1.01, 95% CI = 0.63 - 1.60). The pooled estimate for CYP1A1 A2455G polymorphism was not statistically significantly associated with breast cancer in overall and subgroup analyses. CONCLUSIONS: This meta-analysis provided evidence that CYP1A1 T3801C and A2455G variants might not be risk alleles for breast cancer susceptibility in Chinese individuals. Further studies conducted in other ethnic groups are required for definite conclusions.