Abstract 59P
Background
Hormone receptor positive (HR+)/HER2- metastatic breast cancer (mBC) patients are usually treated with hormonal therapy (HT) plus CDK4/6 inhibitors (CDK4/6i). However, early predictor of response/resitance are lacking. We evaluate the accuracy and feasibility of a novel multi-gene target panel NGS assay for detecting genomic alterations of AKT1, ERBB2, ESR1, KRAS, PIK3CA, and TP53 on circulating tumor DNA (ctDNA) in the plasma of mBC patients undergoing HT and CDK4/6i in relation to clinical early response/resistance.
Methods
In a prospective study (protocol:IRST B114) we collected plasma samples at baseline (T0) and at 3 months (T1) after starting CDK4/6i treatment from patients with advanced HR+/HER2- BC. We selected retrospectively 16 patients, including 8 patients with early resistance at T1 (5 with PD, 3 with stable disease (SD)) and 8 with early response at T1 (8 with partial response (PR)). ctDNA was isolated starting from 2 ml of plasma and libraries were prepared using Plasma-SeqsenseiTM (PQS) Breast Cancer IVD kit (Sysmex Inostics, GmbH) and sequenced by Illumina NEXTSEQ550 platform. NGS data were analysed by PQS IVD Software.
Results
Out of the 5 patients with PD, 1 was wild type for the analysed genes, 3 presented mutations in PIK3CA and 1 in ESR1 genes in T0 sample. Among the 3 PIK3CA mutated patients with PD, 2 showed a higher mutant allele frequency (MAF) in T1 sample, the other patient did not show somatic PIK3CA alteration in T1 sample. Out of the 3 patients with SD, 2 presented KRAS and TP53 gene alterations at baseline which disappeared after 3 months of treatment. Out of 8 patients with PR, 4 (50%) presented alterations of AKT1, TP53, ESR1 and PIK3CA in T0 sample respectively. In all four cases the specific mutation disappeared or dropped drastically after 3 months of treatment. Interestingly, the patient with PI3KCA alteration presented 3 novel ESR1 mutations in the T1 plasma sample.
Conclusions
The liquid biopsy analysis by PQS is feasible and accurate since it provides an absolute quantification of the total number of mutant molecules in the plasma. The presence of PIK3CA and ESR1 alterations was seen predominantly in patients who presented PD.
Legal entity responsible for the study
Lorenzo Stefano Maffioli, General Director of IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori".
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.