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Background: The phosphatidylinositol 3-kinases are known as a family of lipid kinases, playing a role in various cellular processes. A member of this family is PIK3CA which is frequently mutated in breast cancer. In this study, the association between H1047R, E542K and E545K mutations, and therapy resistance was investigated in Iranian breast cancer patients treated by Trastuzumab. Methods: Resistance and sensitive groups were chosen from Iranian patients treated by Trastuzumab. A PCR-RFLP approach was designed for detecting the H1047R mutation. Mutations in positions of codons E542K and E545K were detected using PCR-based DNA Sanger sequencing assay. The overall survival and disease-free survival were assessed. Results: A significant relationship was observed between the presence and absence of H1047R mutation and the overall survival (P = 0.025). In addition, there was a significant relationship between the response to Trastuzumab and some clinicopathological features, including the age and the status of ER/PR receptors (Pvalue< 0.05). E542K and E545K mutations were not observed in the patients. Conclusion: It can be said that probably H1047R mutation is a prognostic marker in the Trastuzumab-based therapy resistant breast cancer. Further studies can be performed to evaluate this mutation before using Trastuzumab to predict the effectiveness of this treatment. [ABSTRACT FROM AUTHOR]

Pregnancy‐associated breast cancer (PABC) is a poor prognosis in women, and the mortality rate is higher in this subgroup of patients than in non‐PABC. This study aims to assess clinicopathological and ultrasound features of patients with PABC. Of 75 patients with breast cancer, 31 cases were in lactating, or pregnancy phase and 44 patients had no recent history of pregnancy/lactation at the time of cancer detection. The available pathological characteristics and ultrasound findings of the PABC and non‐PABC groups were compared. The analysis of ultrasound findings demonstrated that the percentages of antiparallel orientation (p = 0.04) and heterogeneous internal echo pattern (p = 0.002) were higher in the PABC group. The final Breast Imaging Reporting and Data System (BI‐RADS) assessment in the two groups was significantly different (p = 0.008). In this study, most PABCs were BI‐RADS 4c or 5; compared with age‐matched non‐PABC cases. There were significant differences in ER (p = 0.03), receptor groups (p = 0.007), and tumor grade (p = 0.02) in PABC compared to non‐PABC group. To conclude, radiologists should be careful about ultrasound findings of PABC and recommend core needle biopsy in suspected cases. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the most frequent causes of cancer death in women. The application of immunotoxins to target overexpressed biomarkers on the surface of cancer cells and delivery of the toxin molecules into these cells has attracted too much attention during the last decade., Objectives: This study was conducted to investigate the possible in-vitro cytotoxic and apoptotic activity of previously designed recombinant immunotoxin compromising anti-HER2 single-chain variable fragment (scFv) and alpha-luffin protein in human epidermal growth factor receptor type 2 (HER2)-positive and HER2-negative breast cancer cell lines., Materials and Methods: The previously designed recombinant immunotoxin and alpha-luffin protein were expressed in E. coli host cells and purified using Ni-affinity chromatography. The cytotoxicity of the proteins was tested through MTT and apoptosis studies on HER2-positive and HER2-negative breast cancer cell lines., Results: Treatment of SKBR3 and MDA-MB-468 cells with the immunotoxin caused differential cytotoxicity and apoptotic events. Flow cytometry analysis indicated that the immunotoxin could arrest SKBR3 cells at the G0/G1 phase and induce apoptosis and cell death which were not observed in HER2-negative MDA-MB-468 cells. Annexin V/PI staining revealed late apoptotic events in SKBR3 cells treated with the immunotoxin which was different from the early apoptosis induced by the alpha-luffin protein alone., Conclusions: This immunotoxin could be a promising tool in developing new targeted therapeutic agents against HER2-positive cancer cells. Animal experiments are needed before making firmed conclusions., Competing Interests: The authors declare that they have no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)