G. Curigliano (Milan, Italy)
European Institute of OncologyAuthor Of 4 Presentations
Live closing remarks (ID 367)
First-line chemo-IO for mTNBC (ID 17)
Introduction to the ESMO Breast Cancer 2020 Award lecture (ID 281)
Prof. J. Baselga commemoration (ID 323)
Presenter Of 4 Presentations
Prof. J. Baselga commemoration (ID 323)
Live closing remarks (ID 367)
First-line chemo-IO for mTNBC (ID 17)
Introduction to the ESMO Breast Cancer 2020 Award lecture (ID 281)
Moderator Of 4 Sessions
Author Of 3 Presentations
- L. Malorni (Prato, Italy)
- M. Benelli (Prato, Italy)
- F. Galardi (Prato, Italy)
- C. Biagioni (Prato, Italy)
- G. Curigliano (Milan, Italy)
- A. Minisini (Udine, Italy)
- E. Moretti (Prato, Italy)
- E. Risi (Prato, Italy)
- F. De Luca (Prato, Italy)
- A. McCartney (Melbourne, VI, Australia)
- A. Di Leo (Prato, Italy)
- L. Biganzoli (Prato, Italy)
- I. Migliaccio (Prato, Italy)
8P - Mutational analysis of circulating tumor DNA (ctDNA) in patients with ER+/HER2- advanced breast cancer (ABC) receiving palbociclib (P): results from the TREnd trial.
Abstract
Background
Cyclin-dependent kinase 4 and 6 inhibitors like palbociclib (P) are a mainstay of treatment for ER+/HER2- ABC; however intrinsic or acquired resistance is a major clinical issue. We performed a mutational analysis on ctDNA samples from patients (pts) included in the c-TREnd study, the translational cohort of the TREnd trial (NCT02549430) which randomized pts to receive P alone or in combination with the endocrine treatment (ET) to which they had progressed in the previous line of ET.
Methods
Forty-six pts were enrolled in c-TREnd. Plasma was collected before treatment (T0), after the first cycle of therapy (T1) and at the time of progression (T2). Hybridization and capture were performed using the TruSight Tumor 170 Kit (Illumina). Single nucleotide variants (SNVs) were detected and annotated using LoFreq and Oncotator, and further refined by ABEMUS. Tumor Mutational burden (TMB) was the sum of silent and non-silent mutations. Tumor fraction (TF) was based on the dispersion of Copy Number Alteration (CNA) genomic profiles. Progression free survival (PFS) was estimated using the Kaplan–Meier method and compared with the log-rank test.
Results
Thirty-two pts (87 samples), 14 from the P arm and 18 from the P+ET arm, were included in the final analysis. The most frequently mutated genes at T0 were ESR1 (23%), PIK3CA (17%), AR, FGFR2 and TP53 (10%). At T0, mutations in ESR1, but not in PIK3CA, were significantly prognostic (median PFS – mPFS 3.7 mo vs 11 mo in ESR1 mut vs WT, p=0.015). A significantly worse mPFS was observed when a broader analysis of PI3K pathway (adding AKT1, PTEN, TSC1/2 and BRAF) was performed (mPFS 5.2 m in mut vs 10.8 m in WT, p=0.04). Mutations in AR tended to confer a better, although not statistically significant, mPFS (14.2 mo vs 5.5 in WT, p=0.29). At T2 we observed the emergence of 9 new mutations in 7 genes (ESR1, AKT1, ARID1A, BRIP1, CCNE1, MTOR and TP53). TMB and TF at T0 or TF change between T1 and T0 were not associated with PFS.
Conclusions
Mutations in ESR1 and in PI3K pathway genes were associated with worse prognosis in pts treated with P, while TMB and TF were not. Larger studies are needed to validate these observations.
Legal entity responsible for the study
Fondazione Sandro Pitigliani per la Lotta Contro i Tumori ONLUS.
Funding
Pfizer.
Disclosure
L. Malorni: Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Novartis. M. Benelli: Honoraria (self): Novartis. G. Curigliano: Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Veracyte; Advisory/Consultancy: Genomic Health; Honoraria (self): Ellipsis. A.M. Minisini: Advisory/Consultancy: Novartis; Advisory/Consultancy: MSD; Advisory/Consultancy: Pierre Fabre; Speaker Bureau/Expert testimony: SunPharma. E. Risi: Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Amgen; Honoraria (self): Lilly. A. Di Leo: Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: AstraZeneca. L. Biganzoli: Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer. All other authors have declared no conflicts of interest.
24P - Consensus on the utility of breast cancer multigene signatures in routine clinical practice among European Breast Cancer clinicians - The PROCURE project.
Abstract
Background
Several genomic assays are available to profile early breast cancer (BC) that, according to current evidence, can provide reliable information including the risk of recurrence. However, little is known regarding their current use and the perception of utility across Europe. The PROCURE project aims to develop a consensus on the utility of breast cancer multigene signatures (BCMS) in treatment decision making for different eBC patient profiles based on the opinion of a panel of experts.
Methods
A Scientific Committee of 8 experts in BC from 8 European countries developed a Delphi questionnaire to be administered in two-waves to experienced clinicians across Europe, selected based on their experience in BC. The questionnaire includes 5 sections in order to characterize the participants and their expertise in BCMS, to understand the current clinical practice in eBC and the use of BCMS, to recall the participant’s opinion on the utility of the BCMS in eBC according to the patient profiles, to define recommendations on the use of BCMS in clinical practice and finally, to identify unmet needs and future applications of BCMS. 180 participants, including medical oncologists, surgeons, pathologists and gynaecologists, are expected to answer anonymously the online Delphi questionnaire. 70% agreement will be used to determine consensus on a topic.
Results
At the end of January 2021, 146 participants from 11 European countries (Austria, Denmark, France, Germany, Italy, Norway, Portugal, Spain, Sweden, Switzerland and the UK) registered to participate. 61 of them had already fully completed the 1st wave Delphi questionnaire. Results from the 1st wave will be presented to engage larger discussion with congress participants.
Conclusions
The PROCURE Project will provide useful information regarding how BCMS are currently used in clinical practice across Europe and will help to measure the utility attributed to the different BCMS by BC experts for their daily clinical practice, to establish recommendations on the use of BCMS to make treatment decision in different eBC patient profiles and to define current unmet needs and future applications of BCMS according to experts point of view.
Editorial acknowledgement
Adelphi Targis SL.
Legal entity responsible for the study
Veracyte Inc.
Funding
Veracyte Inc.
Disclosure
G. Curigliano: Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Veracyte; Advisory/Consultancy: Genomic health; Advisory/Consultancy: Ellipsis. F. Cardoso: Honoraria (self): Amgen; Honoraria (self): Astellas/Medivation; Honoraria (self): AstraZeneca; Honoraria (self): Celgene; Honoraria (self): Daiichi Sankyo; Honoraria (self): GE Oncology; Honoraria (self): Genentech; Honoraria (self): GlaxoSmithKline; Honoraria (self): Macrogenics; Honoraria (self): Medscape; Honoraria (self): Merck-Sharp; Honoraria (self): Merus BV; Honoraria (self): Mylan; Honoraria (self): Mundipharma; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Honoraria (self): priME Oncology; Honoraria (self): Roche; Honoraria (self): Samsung Bioepis; Honoraria (self): Eisai. M.I. Gnant: Honoraria (self): Veracyte; Honoraria (self): Amgen; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self): Daiichi Sankyo; Honoraria (self): Tolmar; Honoraria (self): LifeBrain. A-V. Lænkholm: Honoraria (self): Veracyte. F. Penault-Llorca: Honoraria (self), Research grant/Funding (self): Veracyte; Honoraria (self), Research grant/Funding (self): Exact science former Genomic Health; Honoraria (self): Agendia; Honoraria (self), Research grant/Funding (self): Myriad. A. Prat: Honoraria (self): Veracyte; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Amgen; Advisory/Consultancy: BMS; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Puma Biotechnology; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: AbbVie; Honoraria (institution): NanoString technologies; Research grant/Funding (institution): Incyte; Honoraria (self): Oncolytics; Honoraria (self), Research grant/Funding (self): Novartis; Advisory/Consultancy: Peptomyc; Honoraria (self), Advisory/Consultancy: Guardian health; Honoraria (self), Shareholder/Stockholder/Stock options: Reveal genomics; Advisory/Consultancy: AstraZeneca; Research grant/Funding (self): Incyte. All other authors have declared no conflicts of interest.
- P. Tarantino (Milan, Italy)
- E. Nicolò (Milan, Italy)
- P. Zagami (Milan, Italy)
- F. Giugliano (Milan, Italy)
- P. Trillo Aliaga (Milan, Italy)
- E. Crimini (Milan, Italy)
- C. Corti (Milan, Italy)
- J. Uliano (Milan, Italy)
- S. Morganti (Milan, Pi, Italy)
- L. Mazzarella (Milan, Italy)
- C. Criscitiello (Milan, Italy)
- A. Esposito (Milan, Italy)
- G. Curigliano (Milan, Italy)
26P - Characterization of low HER2 expressions in de-novo metastatic breast cancer
Abstract
Background
De-novo metastatic breast cancer (MBC) represents a distinct entity, characterized by different genomic and prognostic features compared to relapsed MBC. Although evidence suggests that half of all breast cancers show low HER2 expressions, and that HER2 expressions may increase between the early and metastatic stage, little is known on HER2-low expressions features of de-novo MBC.
Methods
We retrospectively reviewed clinical-pathological data of breast cancer patients consecutively referred to our New Drugs Division (from Jan2014 to Dec2019) with an available pathological analysis of the tumor (on either the primary lesion or a metastatic site). We divided HER2-negative cases by ASCO/CAP 2018 guidelines into an IHC 0 subgroup and a HER2-low subgroup (1+ and 2+/ISH-negative). χ2-test was used for comparisons between categorical parameters.
Results
442 breast cancer patients were eligible for the analysis, of whom 17% (N=75) had de-novo MBC. 65% of all de-novo MBC were luminal-like, 20% were HER2-positive and 15% were triple negative. 43% (n=32) of de-novo MBC showed low HER2-expressions, more commonly among luminal-like (49% HER2-low) than triple negative tumors (32% HER2-low), although this difference was not statistically significant (p=0.17). Compared to de-novo MBC, low HER2-expressions were significantly more common in relapsed MBC (57% vs 43%, p< 0.03). By comparing HER2-expression in relapsed MBC based on the site of sampling, HER2-low expression rate did not differ if the biopsy was performed on breast/lymph nodes or in visceral sites (68% vs 58%, p=0.1). No significant difference was found in low HER2-expression between de-novo MBC and early stage breast cancers (43% vs 44%, p=0.98).
Conclusions
De-novo MBC shows a rate of low HER2-expression comparable with early breast cancer, and significantly lower compared with relapsed MBC. This difference did not appear to be related to the biopsy site. Confirmation of these observations on larger populations of patients is warranted.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
G. Curigliano: Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Seattle Genetics; Honoraria (self): Lilly; Honoraria (self): Ellipses Pharma; Honoraria (self): Foundation Medicine; Honoraria (self): Samsung. All other authors have declared no conflicts of interest.
Presenter Of 1 Presentation
24P - Consensus on the utility of breast cancer multigene signatures in routine clinical practice among European Breast Cancer clinicians - The PROCURE project.
Abstract
Background
Several genomic assays are available to profile early breast cancer (BC) that, according to current evidence, can provide reliable information including the risk of recurrence. However, little is known regarding their current use and the perception of utility across Europe. The PROCURE project aims to develop a consensus on the utility of breast cancer multigene signatures (BCMS) in treatment decision making for different eBC patient profiles based on the opinion of a panel of experts.
Methods
A Scientific Committee of 8 experts in BC from 8 European countries developed a Delphi questionnaire to be administered in two-waves to experienced clinicians across Europe, selected based on their experience in BC. The questionnaire includes 5 sections in order to characterize the participants and their expertise in BCMS, to understand the current clinical practice in eBC and the use of BCMS, to recall the participant’s opinion on the utility of the BCMS in eBC according to the patient profiles, to define recommendations on the use of BCMS in clinical practice and finally, to identify unmet needs and future applications of BCMS. 180 participants, including medical oncologists, surgeons, pathologists and gynaecologists, are expected to answer anonymously the online Delphi questionnaire. 70% agreement will be used to determine consensus on a topic.
Results
At the end of January 2021, 146 participants from 11 European countries (Austria, Denmark, France, Germany, Italy, Norway, Portugal, Spain, Sweden, Switzerland and the UK) registered to participate. 61 of them had already fully completed the 1st wave Delphi questionnaire. Results from the 1st wave will be presented to engage larger discussion with congress participants.
Conclusions
The PROCURE Project will provide useful information regarding how BCMS are currently used in clinical practice across Europe and will help to measure the utility attributed to the different BCMS by BC experts for their daily clinical practice, to establish recommendations on the use of BCMS to make treatment decision in different eBC patient profiles and to define current unmet needs and future applications of BCMS according to experts point of view.
Editorial acknowledgement
Adelphi Targis SL.
Legal entity responsible for the study
Veracyte Inc.
Funding
Veracyte Inc.
Disclosure
G. Curigliano: Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Veracyte; Advisory/Consultancy: Genomic health; Advisory/Consultancy: Ellipsis. F. Cardoso: Honoraria (self): Amgen; Honoraria (self): Astellas/Medivation; Honoraria (self): AstraZeneca; Honoraria (self): Celgene; Honoraria (self): Daiichi Sankyo; Honoraria (self): GE Oncology; Honoraria (self): Genentech; Honoraria (self): GlaxoSmithKline; Honoraria (self): Macrogenics; Honoraria (self): Medscape; Honoraria (self): Merck-Sharp; Honoraria (self): Merus BV; Honoraria (self): Mylan; Honoraria (self): Mundipharma; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Honoraria (self): priME Oncology; Honoraria (self): Roche; Honoraria (self): Samsung Bioepis; Honoraria (self): Eisai. M.I. Gnant: Honoraria (self): Veracyte; Honoraria (self): Amgen; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self): Daiichi Sankyo; Honoraria (self): Tolmar; Honoraria (self): LifeBrain. A-V. Lænkholm: Honoraria (self): Veracyte. F. Penault-Llorca: Honoraria (self), Research grant/Funding (self): Veracyte; Honoraria (self), Research grant/Funding (self): Exact science former Genomic Health; Honoraria (self): Agendia; Honoraria (self), Research grant/Funding (self): Myriad. A. Prat: Honoraria (self): Veracyte; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Amgen; Advisory/Consultancy: BMS; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Puma Biotechnology; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: AbbVie; Honoraria (institution): NanoString technologies; Research grant/Funding (institution): Incyte; Honoraria (self): Oncolytics; Honoraria (self), Research grant/Funding (self): Novartis; Advisory/Consultancy: Peptomyc; Honoraria (self), Advisory/Consultancy: Guardian health; Honoraria (self), Shareholder/Stockholder/Stock options: Reveal genomics; Advisory/Consultancy: AstraZeneca; Research grant/Funding (self): Incyte. All other authors have declared no conflicts of interest.