Abstract PS5-44: Pik3ca mutations among hormone receptor positive and HER-2 negative advanced breast cancer patients in Finland
Authors: Heinolainen Krista , Saarinen Silva , Ellonen Antti , Karlsson Antti , Utriainen Meri , Vertuani Simona , Holm Barbro 
Published: February 2021

Abstract
Background: Several new medicinal products have been introduced for the treatment of advanced breast cancer (aBC) in recent years, many of which are indicated for a specific patient population. One of these compounds is alpelisib, a phosphatidylinositol 3-kinase (PI3K) inhibitor, which has shown efficacy in the treatment of hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) advanced breast cancer (aBC) harboring phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) “hotspot” mutations, i.e. mutations affecting the helical (E542K and E545K) and kinase (H1047R) domains. In this retrospective register-based study, the frequency of PIK3CA gene mutations as well as survival among HR+/HER2- aBC patients in Finland was analyzed.
Methods: This study utilized retrospective register-based data from the Hospital District of Southwest Finland (Auria Biobank), which covers approximately 20% of the population in Finland. Patients diagnosed with aBC between 2004─2013 were identified using ICD-10 code C50* (breast cancer) together with customized text mining algorithms to extract metastatic patients. Tumor biomarker data including estrogen receptor (ER), progesterone receptor (PR), and HER2 status were used to identify HR+/HER2- patients. The formalin fixed paraffin embedded (FFPE) tumor tissue samples available for these patients in the Auria Biobank’s tissue archives were screened for PIK3CA mutations with next generation sequencing. Study follow-up period was defined to start from the date of aBC diagnosis and to continue until death or end of 2016, whichever occurred first. Clinical pathology and survival data were collected from the Auria Biobank and electronic medical records of the Hospital District of Southwest Finland. Overall survival (OS) was estimated using the Kaplan-Meier method.
Results: Altogether 444 adult female patients with aBC were identified. HR and HER2 status were available for 377 patients (85%), out of which 274 (73%) were HR+/HER2-. Representative FFPE tumor samples were available for 187 patients and PIK3CA was successfully screened in 161 patients. Out of the sequenced HR+/HER2- samples, 53.4% showed mutation in the PIK3CA gene and 46.6% wild type (wt) PIK3CA gene. Approximately one third (32.3% n=52) of the samples represented PIK3CA hotspot mutations and 18% (n=29) of these displayed more than one PIK3CA variant. The most common PIK3CA hotspot mutation was H1047R. HR+/HER2- patients with the wt PIK3CA gene showed slightly shorter OS compared to patients showing PIK3CA hotspot mutations (18.9 months (95% CI: 14.1-25.1) vs. 22.3 months (95% CI: 17.0-26.3). Higher portion of the wt patients also developed metastases within 1 year from the primary diagnosis compared to the patients with PIK3CA hotspot mutations (41.3% vs. 25.0%). At the time of diagnosis, 92.0% of the wt and 84.6% of the PIK3CA hotspot mutated population was 50 years or older, respectively.
Conclusion: Approximately one third of the HR+/HER2- aBC patient cohort in Finland had at least one variant of PIK3CA hotspot mutations in line with the SOLAR-1 clinical trial population. The OS did not differ markedly between the patients with wt and hotspot mutated PIK3CA gene. The short OS of the patients is probably due to the fact that the patients were treated before the availability of CDK4/6is as a treatment option.
Citation Format: Krista Heinolainen, Silva Saarinen, Antti Ellonen, Antti Karlsson, Meri Utriainen, Simona Vertuani, Barbro Holm. Pik3ca mutations among hormone receptor positive and HER-2 negative advanced breast cancer patients in Finland [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-44.