Abstract 2616
Background
The identification of biomarkers to drive treatment is one of the most important objectives of precision medicine. During last years, the role of PIK3CA mutations have been related to clinical benefit deriving from treatment with PI3K, and mTOR inhibitors. In breast cancer (BC), PIK3CA mutations are widely present and the use, in clinical trials, of selective inhibitors improved clinical outcomes. The aim of this study is to assess the value of a monocentric genomic screening program to select patients for trials with experimental targeted agents.
Methods
We examined PIK3CA mutation in a cohort of 312 metastatic BC patients diagnosed at Hospital Clínico València-INCLIVA from Jan-13 to Apr-19. The sequencing of hotspot mutations was performed in primary (29.9%) and metastatic tissue (70.1%). We used two different technologies: MassARRAY technology (Sequenom MassARRAY, OncoCarta v1.0) and Iluminia MiSeq System (customised panel, OncoSpot v.1). Hotspots were selected according to databases already published. To be diagnosed as mutated, tumors needed to harbor at least 5% of mutant alleles. 7 clinical trials against PI3K pathway were available.
Results
PIK3CA analysis was performed in 312 paraffin embedded tumor samples, in which only 5.8% the analysis was not possible due to low quality of DNA. The distribution of BC subtypes were 77.6% Luminal, 13.9% HER2, and 8.5% triple negative (TN). PIK3CA mutations were detected in 96 patients (32.7%). In Luminal, PIK3CA mutations reached 36.8% while only 19.5% in HER2 and 16.0% in TN, respectively. A wide spectrum of PIK3CA mutations was found: H1047R (38.5%), E545K (30.2%), E542K (19.8%), R88Q (3.1%), M1043I (3.1%), N345K (2.1%), P539R (1.0%), K111E (1.0%), C420R (1.0%). One hundred and ninety (64.6%) patients were included in clinical trials, and 74 (38.9%) were treated with PI3K, AKT and mTOR inhibitors.
Conclusions
PIK3CA mutations were widely present among luminal BC, being actually a specific target for new drugs. PIK3CA mutational analysis was easily and successfully performed in our center. The identification of PIK3CA hotspots mutations lead to the access for our patient to novel drugs into clinical trials, achieving relevant clinical benefits in most of the cases.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Lluch: Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Eisai; Advisory / Consultancy: Celgene. A. Cervantes: Advisory / Consultancy: Merk serono; Advisory / Consultancy: Roche; Advisory / Consultancy: Beigine; Advisory / Consultancy: Bayer; Advisory / Consultancy: Servier; Advisory / Consultancy: Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Takeda; Advisory / Consultancy: Astelas; Advisory / Consultancy: Pierre Fabre; Speaker Bureau / Expert testimony: Foundation Medicine. All other authors have declared no conflicts of interest.
Resources from the same session
2107 - Role of Individualized Intervention(s) on Quality of Life (QOL) and Adherence to Adjuvant Endocrine Therapy in Premenopausal Women with Early-Stage Breast Cancer (BC): MyChoice Study
Presenter: Shahid Ahmed
Session: Poster Display session 2
Resources:
Abstract
5812 - Correlation between the density of tumor-infiltrating lymphocytes, immune cell subsets in tumor stroma and response to systemic therapy in breast cancer
Presenter: Cvetka Grasic Kuhar
Session: Poster Display session 2
Resources:
Abstract
4734 - BRCA1/2 Testing in HER2- Advanced Breast Cancer (ABC): Results from the European Component of a Multi-Country Real World Study
Presenter: Michael Patrick Lux
Session: Poster Display session 2
Resources:
Abstract
1686 - In vitro and in vivo rescue of resistance to BET inhibitors by targeting PLK1 in triple negative breast cancer.
Presenter: Cristina Nieto-jiménez
Session: Poster Display session 2
Resources:
Abstract
5020 - Neoadjuvant endocrine therapy in combination with melatonin and metformin in locally advanced breast cancer
Presenter: Tatiana Semiglazova
Session: Poster Display session 2
Resources:
Abstract
5082 - Melatonin and metformin in neoadjuvant chemotherapy in locally advanced breast cancer
Presenter: Tatiana Semiglazova
Session: Poster Display session 2
Resources:
Abstract
2642 - Patient-tailored tamoxifen dosing based on an increased quantitative understanding of its complex pharmacokinetics: A novel integrative modelling approach
Presenter: Anna Mueller-Schoell
Session: Poster Display session 2
Resources:
Abstract
2461 - Lack of benefit of neoadjuvant pertuzumab in high risk HER2 positive breast cancer. A retrospective case-control study of 355 cases with biomarker analysis.
Presenter: Manuela Tiako Meyo
Session: Poster Display session 2
Resources:
Abstract
4776 - Targeting CDCA3 to improve chemotherapy response in triple-negative breast cancer patients
Presenter: Kenneth O'Byrne
Session: Poster Display session 2
Resources:
Abstract
1674 - Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer
Presenter: María Del Mar Noblejas López
Session: Poster Display session 2
Resources:
Abstract