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
3330 - Tumour-infiltrating lymphocytes and BRCA-like status in stage III breast cancer patients treated with intensified carboplatin-based chemotherapy
Presenter: Leonora De Boo
Session: Poster Display session 2
Resources:
Abstract
3971 - Unravelling the biological characteristics of MammaPrint extreme risk subgroups
Presenter: Rajith Bhaskaran
Session: Poster Display session 2
Resources:
Abstract
5871 - Residual Cancer burden as a prognostic factor in a large series of Neoadjuvant chemotherapy. Subgroup analysis per molecular surrogated subtypes
Presenter: Catalina Falo
Session: Poster Display session 2
Resources:
Abstract
5014 - Clinical validation of CanAssist Breast in a Spanish cohort
Presenter: Manjiri Bakre
Session: Poster Display session 2
Resources:
Abstract
2787 - Meta-analysis on association of pathological complete response with long-term survival outcomes in triple-negative breast cancer
Presenter: Peter A. Fasching
Session: Poster Display session 2
Resources:
Abstract
4301 - Immune infiltrate composition across intrinsic subtypes in hormone receptor (HR)+/HER2- early breast cancer (BC) enrolled in the prospective LETLOB trial
Presenter: Gaia Griguolo
Session: Poster Display session 2
Resources:
Abstract
3205 - Frequency of germline mutations in women's cancer susceptibility genes in a large cohort of Chinese breast cancer patients
Presenter: Ning Liao
Session: Poster Display session 2
Resources:
Abstract
4091 - Triple blinded Prospective Study assessing the Impact of Genomics & Artificial Intelligence Watson For Oncology (WFO) on MDT’s Decision of Adjuvant Systemic Therapy for Hormone Receptor Positive Early Breast Carcinoma-
Presenter: Somashekhar Sampige Prasannakumar
Session: Poster Display session 2
Resources:
Abstract
4359 - Prognostic significance of Progesterone Receptor levels in luminal-like Her2- early Breast Cancer patients. A retrospective single Cancer Center analysis.
Presenter: Anna Diana
Session: Poster Display session 2
Resources:
Abstract
1369 - PAM50 HER2-enriched subtype and pathological complete response in HER2-positive early breast cancer: a meta-analysis
Presenter: Francesco Schettini
Session: Poster Display session 2
Resources:
Abstract