Neoadjuvant Trastuzumab and Pertuzumab in Combination with Standard Chemotherapy for HER2-Positive Early Breast Cancer: Real-World Practice in Cuba.

PURPOSE: Dual HER2 blockade chemotherapy is the standard of care for localized HER2+ breast cancer (BC). However, despite the efficacy of neoadjuvant therapy, relapses occurring in around 10% of patients highlight the need to improve its clinical approach. Therefore, this study aimed to evaluate the effectiveness/safety of neoadjuvant therapy with subcutaneous (SC) trastuzumab- pertuzumab chemotherapy (real world) to extend the evidence, which comes mainly from clinical trials (selected population; intravenous [IV] trastuzumab). MATERIALS AND METHODS: A prospective, longitudinal, observational study in a Cuban hospital. POPULATION: women aged ≥18 years with histologically confirmed HER2+ early-stage BC (2017-2021) eligible for neoadjuvant treatment (IV pertuzumab, SC trastuzumab, taxane-based chemotherapy). The aim was to determine the pathological complete response (pCR) rate to this scheme, its safety, and the impact of patient's characteristics on the outcomes. RESULTS: Eighty-seven women were included: n=29 (DPT [docetaxel-IV pertuzumab- SC trastuzumab 600 mg; 4 cycles]); n=58 (ddAC-DPT [dose-dense anthracycline-based scheme+DPT]; 8 cycles). The median age was 57 years (range 30-83), ECOG 0: 97%. Time from diagnosis to treatment (median) was 28 days. The overall pCR rate was 62.1% (55.2%, DPT; 66.5%, ddAC-DPT; p =0.351); HR+, 47.7% vs. HR-, 76.7% (p=0.006). There were no statistically significant differences based on nodal status, stage, or Ki-67 levels. Overall, 94.2% of patients experienced ≥1 adverse event related to treatment, all of them grade 1-3 and more common with ddAC-DPT. The main cause of treatment delays (n=19; ddAC-DPT, 16; DPT, 3) was treatment-related toxicities. CONCLUSION: Neoadjuvant trastuzumab (SC) and pertuzumab plus chemotherapy for HER2+ early-stage BC showed benefits in a real-life setting, with an acceptable safety profile.

Immunoreactivity of the 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside in Primary Lymphoid Tumors and Lymph Node Metastasis.

The reactivity of the 14F7 Mab, a highly specific IgG1 against N-glycolyl GM3 ganglioside (NeuGcGM3) in normal tissues, lymphomas, lymph node metastasis, and other metastatic sites was assessed by immunohistochemistry. In addition, the effect of chemical fixation on the 14F7 Mab staining using monolayers of P3X63Ag.653 cells was also evaluated. Moreover, the ability of 14F7 to bind NeuGcGM3 ganglioside inducing complement-independent cytotoxicity by a flow cytometry-based assay was measured. The 14F7 Mab was reactive in unfixed, 4% paraformaldehyde, 4% formaldehyde, and acetone fixed cells. Postfixation with acetone did not alter the localization of NeuGcGM3, while the staining with 14F7 Mab was significantly eliminated in both cells fixed and postfixed with methanol but only partially reduced with ethanol. The staining with 14F7 Mab was evidenced in the 89.2%, 89.4%, and 88.9% of lymphomas, lymph node metastasis, and other metastatic sites, respectively, but not in normal tissues. The treatment with 14F7 Mab affected both morphology and membrane integrity of P3X63Ag.653 cells. This cytotoxic activity was dose-dependent and ranged from 24.0 to 84.7% (10-1000 µ g/mL) as compared to the negative control. Our data could support the possible use of NeuGcGM3 as target for both active and passive immunotherapy against malignancies expressing this molecule.