PIK3CA mutation presence as luminal breast cancer chemoresistance prognostic marker

Abstract

Author(s): Movchan Oleksii Volodimirovich, Smolanka Ivan Ivanovich, Lyashenko Andriy Oleksandrovich, Dosenko Irina Viktorivna, Loboda Anton Dmitrovich, Ivankova Oksana Mykolaivna

Breast Cancer (BC) is the major cause of morbidity and mortality among women in Ukraine and throughout the world, is characterized by a diverse set of gene alterations, the interaction between the tumor's molecular and genetic properties and the prognostic and clinical aspects. The National Comprehensive Cancer Network's (NCCN) Clinical Practice Guidelines for Breast Cancer indicate anthracycline with cyclophosphamide and taxane as a recommended Neoadjuvant Chemotherapy (NAC) strategy. Despite advances in disease prognosis and the overall advantages of chemotherapy, BC treatment frequently generates miscellaneous results in various groups. Drug resistance is a significant cause of cancer therapeutic failure. There is critical to investigate additional gene polymorphisms that may affect BC therapy responses. PIK3CA mutations are seen in around 25%-45% of BC, and they are more common in Hormone Receptor-Positive (HR+ ) patients. Although data have been extensively reported in BC, no study has focused on the molecular characterization and clinical outcome of patients with PIK3CA-mutated Chemo-resistant (ChR) BC. According to researches, the oncogenic PIK3CA mutation pathway, in conjunction with other pathways, induces tumor aggressiveness and chemo-resistance. Therefore a need to better understand the characteristics of the ChRBC population harboring PIK3CA mutations. Resistance to neoadjuvant chemotherapy is related with PIK3CA mutations. This biomarker will be studied further for therapeutic utility in the treatment of luminal ChRBC patients. PIK3CA mutation was found to be unfavorable in patients with both overall and luminal BC, demonstrating the potential of PIK3CA mutation in combination with other multiple gene alterations and their relationships among themselves as detailed prognostic indicators in BC resistance subgroups. When the response to NAC and prognosis of breast cancer-intrinsic subtypes were evaluated, patients with luminal tumors had a lower pathologic complete response rate, but better outcomes than triple negative and HER2 types. Similarly, luminal tumors with PIK3CA mutations exhibited chemo-resistance when compared to PIK3CA wild-type.

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