BRAF, KRAS and PIK3CA Mutation and Sensitivity to Trastuzumab in Breast Cancer Cell Line Model.

Dear Editor

I have read with interest the article in this journal by Patra et al., (2017) concerning BRAF, KRAS and PIK3CA mutation and sensitivity to trastuzumab in breast cancer cell line model. They evaluated trastuzumab responsiveness in breast cancer (BCa) cell lines. They showed the optimum concentration of trastuzumab to be 7 μg/well. Moreover, they detected BRAF and KRAS mutated cell line, MDA-MB-231, found the least sensitivity after being treated with trastuzumab when to the sensitivity of the PIK3CA mutated cell lines, MCF-7 and MDA-MB-361, and KRAS-BRAF-PIK3CA cell line, MDA-MB-453.

Phosphatidylinositol-4,5-bisphosphate 3 kinase catalytic subunit α (PIK3CA), which is located on chromosome 3, encodes the catalytic subunit p110α of class IA phosphoinositide 3-kinase (PI3K). Also, PIK3CA is one of the most commonly mutated oncogenes in several types of human cancer, including breast, colon and endometrial cancer (Cizkova et al., 2013; Dirican et al., 2016). In 2014, we aimed PIK3CA mutations in BCa investigating clinical and prognostic significances (Dirican et al., 2014). And frequency of PIK3CA mutations found 31%, should be diagnostic significance (Dirican et al., 2014). We believe the potential of PIK3CA mutations as an important biomarker for BCa classification and the possible use of PIK3CA inhibitor as targeted therapy for BCa. Therefore, we need to increase the number of trials on the PIK3CA gene in vivo and in vitro. In the future, these trials will help to choice correct treatment models. Patra et al., (2017) showed that the cell line most sensitivite to trastuzumab is MDA-MB-453 with the PIK3CA. This findings are important which indicates the potential mechanism for trastuzumab resistance. Especially, HER-2 positive BCa cells were treated with combining trastuzumab with a PIK3CA inhibitor agent. A recent study reported that PIK3CA (E542K) were found to be significantly associated with reduced disease-free survival (DFS) in patients treated with trastuzumab (p: 0.018 and 0.005, respectively) (Singla et al., 2019). This study implied that PIK3CA genes are important biomarkers in HER2+ BCa. Also, the patients harboring mutant PIK3CA exhibit a poorer clinical outcome as compared to those carrying wild-type PIK3CA. PIK3CA mutation analysis can be usefully performed in real-life clinical practice (Cociolone et al., 2018). Investigation of the molecular mechanism of PIK3CA and its related genes is important for BCa treatment.