The role of PIK3CA gene mutations in breast cancer
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Shadi Tanhadokht,1,*
1. Alborz University
- Introduction: Today, breast cancer is one of the most common cancers among women and at the same time one of the most important diseases in the world. Epidermal growth factor 2 (HER2) receptor, a member of the epidermal growth factor (EGF) family , which is highly expressed in a large proportion of breast cancers. Trastuzumab or Herceptin is a monoclonal antibody that acts as an anti-HER2 agent for targeted therapies , Patients treated with HER-2 overexpression are treated, Therefore, for some HER2 + breast cancer patients, trastuzumab is not beneficial and breast cancer in these patients spreads or spreads over time. . The PI3K pathway is a family of lipid kinases that phosphorylates the 3OH group of phosphatidylinositol, PI3K has alpha (α), beta (β) and gamma (γ) subunits. The alpha subunit (PI3KCA) plays a much more important role in the transmission of cancer messages, and various studies have been performed on it. Activation of PI3K activates a message cascade that promotes the growth, survival, and metabolism of cancer cells. The PIK3CA gene encodes the alpha catalytic subunit of the PI3K enzyme. PIK3CA mutations indicate resistance to trastuzumab therapy by activation of the PI3K / AKT pathway. The aim of this study was to evaluate the frequency of mutations in common points of PIK3CA gene, including exons 9 and 20, in HER2 + breast cancer patients resistant to trastuzumab , compared with patients who responded to treatment.
- Methods: In this case-control study, a number of control and paraffin-embedded breast tissue samples from HER2 + ductal carcinoma patients who were treated with Transtuzumab for one year. After examining the variables to be studied by the oncologist, samples were collected from the Breast Cancer Research Institute and the tumor bank of Imam Khomeini Hospital in Tehran and examined. The age range of patients was between 27 and 67 years and their mean age was 47 years . These patients were evaluated for age and type, size, grade and stage of the tumor and the number of lymph nodes involved, and Stage 4 patients were not included in the study. Also information about the presence of tumor markers such as HER2, ER, PR . Patients' medication regimens were also evaluated. DNA extraction was performed from the samples and PCR test was optimized using breast cancer tissue samples expressed in exon 9 and exon 20 of PI3KCA gene and positive and negative control along with the size of the marker. Primers were optimized and used. Finally, Sanger method was used to sequence exons 9 and 20 of PIK3CA gene in this study, which was performed by Macrogen Company of South Korea.
- Results: Out of 52 patients included in the plan, 23 (44%) were identified as herceptin resistant and 29 (55%) as sensitive to herceptin.The age range of patients was between 27 and 67 years and their mean age was 47 years. All patients were HER2 (+3) and had received herceptin.30 patients (57%) had ER + tumor marker and 24 patients (46%) had PR + tumor marker.In this study, nucleotide changes including 67039G˃T on exon 9 and 86860C˃G on exon 20 were observed. The frequency of G70T 67039 in the group of susceptible patients was 7.7% but this mutation was not observed in the group of resistant patients.Odds ratio for this jump was 0.12 (95% CI: 0.1983 to 3.2842) and P = 0.1.. The frequency of 86860CGG on exon 20 was 17.4% in the group of resistant patients and 20.7% in the group of susceptible patients.The Oddsratio ratio for this mutation was 0.8 (95% CI: 0.0062 to 2.3620) and P = 0.7.
- Conclusion: Trastuzumab is in fact an effective and essential anti-cancer drug in the treatment of people with breast cancer. A significant number of patients after initial treatment with a diet containing trastuzumab, their disease progresses progressively and requires the addition (continuation) of the treatment process. The results of this study showed a mutation in PIK3CA gene in HER2-positive breast cancer patients treated with trastuzumab, but the study of the presence of these mutations in two groups resistant and sensitive to trastuzumab and calculating the amount of these mutations in both groups, a significant relationship between this Mutations with resistance to trastuzumab treatment were not observed. The mutations found in this study included 67039G˃T on exon 9 and 86860CG on exon 20, of which 67039G˃T was not observed in the group of sensitive patients with a frequency of 7.7% and in the group of resistant patients.
- Keywords: Transtomazob , HER2, PI3K, Breast cancer, , Mutations
