280P - Adjuvant aromatase inhibitors in patients with PIK3CA mutation early breast cancer

Background

Phosphatidylinositide-3-kinase (PI3K) regulates proliferation and apoptosis and; somatic PIK3CA-mutations may activate these processes. In a prospective cohort study of early breast cancer (eBC) patients, in case of somatic PIK3CA-mutation we observed resistance to aromatase inhibitor (AI) therapy (Reinhardt K et al., Breast Cancer Res Treat 2022 ;196:483–493). This study is aimed at validating these findings in a second cohort.

Methods

We studied a unicentre cohort of 262 patients with steroid hormone receptor-positive, HER2-negative eBC, who were planed to be treated with endocrine therapy only: aromatase inhibitor (AI, n=183) or Tamoxifen (TAM, n=69), AI and TAM (n=9), Fulvestrant (n=1) and tested the three most common somatic PIK3CA gene mutations (H1047R, E545K, E542K) by qPCR. The primary endpoint was recurrence-free survival (RFS), secondary endpoint overall survival (OS). Median follow up was 62 months.

Results

The PIK3CA-mutation rate was 42% (110 of 262). Overall, there was no difference considering RFS between patients with AI (n=183) and TAM (n=69) therapy (5 yrs-RFS 91.7% in both groups). Patients of the AI group harbouring a somatic PIK3CA mutation (n=75) had non-significantly more RFS related events compared to patients with PIK3CA wildtype (n=108): 5 yrs-RFS 89.5% (95% CI 82.1-97.0) versus 93.2% (95%CI 87.9 - 98.5), respectively (HR=1.2, 95%CI 0.461-2.961; n.s.). After 5 yrs, 91.2% (95% CI 84.5 – 97.9) of the patients with PIK3CA mutation were alive and 94.4% (95% CI 89.7 – 99.1) of patients without PIK3CA mutation, respectively (HR=1.3, 95% CI 0.453-3.447; n.s.). In the group of patients who were treated with TAM only (n=69), no interaction was observed between PIK3CA mutation and RFS or OS, respectively.

Conclusions

Although we observed a trend that AIs are less effective in patients with PIK3CA mutated tumours, formal validation is still lacking. Further data including prospective studies are required.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. Thomssen: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Aurikamed, Daiichi Sankyo, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, Nanostring, Novartis, Onkowiisen, Pfizer, Roche, Seagen, Vifor; Financial Interests, Personal, Financially compensated role: Forum Sanitas; Non-Financial Interests, Personal, Member: AGO Breast committee, ASCO, DGGG, DGS, DKG, EORTC; Non-Financial Interests, Personal, Member of Board of Directors: AGO-B Breast Study Group; Non-Financial Interests, Personal, Officer: BIG; Non-Financial Interests, Personal, Invited Speaker: ESO; Non-Financial Interests, Personal, Steering Committee Member: ESMO. All other authors have declared no conflicts of interest.