33P - Somatic mutations of PIK3CA and AKT1 in Japanese breast cancer

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Breast Cancer
Translational Research
Presenter Tatsunori Shimoi
Citation Annals of Oncology (2016) 27 (suppl_9): ix9-ix18. 10.1093/annonc/mdw574
Authors T. Shimoi1, A. Hamada2, Y. Kitamura1, T. Nishijo2, A. Shimomura1, C. Shimizu1, M. Yoshida3, T. Kinoshita4, Y. Fujiwara1, K. Tamura1
  • 1Breast And Medical Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 2Department Of Clinical Pharmacology, Fundamental Innovative Oncology Core, National Cancer Center Research Institute, 104-0045 - Tokyo/JP
  • 3Departement Of Pathology And Clinical Laboratories, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 4Departement Of Breast Surgery, National Cancer Center Hospital, 104-0045 - Tokyo/JP

Abstract

Background

PI3K/AKT/mTOR pathway regulates cell proliferation, growth and survival. The PIK3CA mutation is one of the most frequent somatic mutation in breast cancer and its frequency is about 30%. The AKT1 mutation is considered to be drivers of human breast cancer, and frequency is about 3%. However, there are few reports about frequencies in Asian breast cancer population. We tried to reveal the frequency of the PIK3CA and AKT1 mutations in the Japanese cohort.

Methods

We retrospectively analyzed 337 samples from breast cancer patients who were treated in National Cancer Center Hospital. We extracted DNA and determined three hotspot PIK3CA mutations (E542K, E545K, H1047R) with quenched probe system, or AKT1 E17K mutation with PNA-LNA clamp methods. Differences between proportions for categorical variables were analyzed using the chi-square statistic. Kaplan-Meier analysis was performed to analyze event-free survival (EFS) after surgery and overall survival (OS).

Results

We analyzed PIK3CA mutation in 334 samples or AKT1 mutation in 329 samples, from breast cancer patients who was treated between January 2008 and June 2015. Three hundred and five patients were initially stage I to III, and thirty-two patients were initially StageIV. The number of tumor subtype was hormone receptor (HR) positive and HER2 negative tumor; 248 (74%), HR positive and HER2 positive tumor; 44 (13%), HR negative and HER2 positive tumor; 28 (8%), and Triple negative tumor; 17 (5%), respectively. The median age was 52 (range 22-90). There are 176 relapses and 32 deaths. We could detect 111 patients with PIK3CA mutations (33%) in 334 patients and 24 patients with AKT1 mutation (7.3%) in 329 patients. Twenty patients (6%) had E542K mutation, 21 patients (6%) had E545K mutation and 74 patients (22%) had the H1047R mutation. PIK3CA mutations were no difference between the four subtypes, however, AKT1 mutation was highly frequent in HR positive HER2 negative breast cancer (p = 0.038). PIK3CA mutation was a statistically significant good prognostic factor by EFS (p = 0.018), especially at the spot of H1047R (p = 0.008), but not by OS.

Conclusions

Although the frequency of PIK3CA mutation was equivalent between races, AKT1 mutation seemed to be more frequent in Japanese than in Caucasian.

Clinical trial indentification

Legal entity responsible for the study

N/A

Funding

Initiative for Accelerating Regulatory Science in Innovative Drug, Medical Device, and Regenerative Medicine’, and a Grant-in-Aid for Cancer Research from the National Cancer Center to A. H.

Disclosure

All authors have declared no conflicts of interest.