Abstract 6448: Prevalence and spectrum of PIK3CA mutations in Indian breast cancer patients
Authors: Katara Rahul , Bhardwaj Tina , Rawat Monika , Sharma Deepak K. , Kumar Vipin , Sharma Shivani , Dagar Vaishali , Kumar Pawan , Mohanty Sambit K. 
Published: March 2024

Introduction: Breast carcinomas are the most commonly encountered cancers in women globally. Due to advancements in cancer research the death rate in breast cancer has reduced by 41% since 1989; however, the downward trend has recently slowed emphasizing on new breast carcinomas treatment discovery. Breast carcinomas are molecularly categorized by the expression of specific hormone receptors, as well as the overexpression of human epidermal growth factor receptor 2 (HER2). Approximately 80% of breast cancers have been termed HER2-negative, but researchers now recognize that 55% of all breast cancers may actually contain low levels of HER2, levels that are still targetable by HER2-directed therapies such as Trastuzumab Deruxtecan. The phosphoinositide 3-kinase (PI3K) pathway is the most frequently altered pathway in HR+/HER2- breast carcinomas and is associated with tumor development, disease progression, and endocrine resistance.

Methodology: The study entailed histological verification of breast cancer, and thence the extraction of DNA from formalin fixed, paraffin embedded (FFPE) tissue samples. A tumor content of 20% was the cut-off for performing the PIK3CA mutation analysis. The DNA was subjected to mutation analysis using a FDA-approved PIK3CA RGQ Real Time PCR based assay that has ability to detect 11 mutations in the PIK3CA gene encompasses exons 7, 9, and 20.

Results: A total of 696 breast cancer patient samples (with more than 20% neoplastic tissue content) were screened for PIK3CA mutations. Of these, 275 (39.5%) (Male: Female ratio = 1:26.5; Age range = 30-80 years) harbored a mutation of the PIK3CA gene. Females were commonly affected; however, the males were also found to have PIK3CA mutation. The most common affected age group is from 41 to50 years. The positivity rate exon wise were as follows: Exon 7 (1.45%), Exon 9 (39.27%), and Exon 20 (44.27%). There was presence of co-mutations amongst different exons, which comprised of 4%. HR+/HER2- (50%) followed by HR-/Her2- (3.27%) and HR+/HER2+ (1.82%). The HER2- cases (Score 1 and Score 2) by IHC were considered as low positive cases (14%).

Conclusion: This is one of the largest study to report frequency of PIK3CA mutations in the Indian population. PIK3CA mutations are commonly encountered in hormone receptor positive and HER2 Negative metastatic breast cancer and have shown promising clinical outcome leading to better prognosis. It provides insights into genotyping each breast cancer and exploits the usage of PI3K/AKT inhibitors together with other combination of drugs for effective target treatment strategies.

Keywords: Breast carcinomas, PIK3CA, HR/HER2, Targeted Therapeutic

Citation Format: Rahul Katara, Tina Bhardwaj, Monika Rawat, Deepak K. Sharma, Vipin Kumar, Shivani Sharma, Vaishali Dagar, Pawan Kumar, Sambit K. Mohanty. Prevalence and spectrum of PIK3CA mutations in Indian breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6448.