Abstract 52P
Background
We aimed to describe the molecular landscape of de novo versus recurrent metastatic breast cancer (dnMBC and rMBC).
Methods
Clinical and molecular data from patients with MBC were collected from the molecular tumour board at Gustave Roussy. Genomic analyses were carried out by liquid or solid biopsies (FoundationOne® Liquid CDx assay and FoundationOne® Tissue CDx, respectively; both covering 324 genes), performed during disease evolution as per investigator choice. Descriptive statistics were performed using R studio version 4.1.1.
Results
We identified 668 patients with genomic data, from whom 564 had available clinical data: 464 patients with liquid biopsy (141 dnMBC; 323 rMBC) and 100 (21 dnMBC; 79 rMBC) patients with a tissue-based assay. Overall, there was no significant difference in the median number of mutations (Mut), copy number variants (CNV), rearrangements (Rearrang) or Tumour Mutational Burden (TMB) detected between dnMBC and rMBC. A higher median number of mutations were noted on ctDNA-based assays compared to tissue-based assays (12 versus 9, p-value <0.05). On ctDNA-based assays, 85-100% of patients had at least one alteration detected in both dnMBC and rMBC, regardless of BC subtype. The table summarizes percentage of patients having at least one alteration in breast cancer subtypes. The most frequently altered genes in dnMBC were ATM, ESR1, PIK3CA and TP53on ctDNA; ATM, BRCA2, LTK, PIK3CA and TP53 on tissue. In rMBC, the most frequently altered genes were ATM, CHEK2, ESR1, PIK3CA and TP53on ctDNA; ARID1A, BRCA2, MAP3K1, PIK3CA and TP53 on tissue. Differences in genomic landscape between dnMBC and rMBC for each specific subtype will be presented at the congress. Table: 52P
| dnMBC liquid (%) | rMBC liquid (%) | dnMBC tissue (%) | rMBC tissue (%) | |
| TN | ||||
| Rearrang | 45 | 45 | 8 | 35 |
| CNV | 26 | 26 | 33 | 62 |
| Mut | 89 | 85 | 42 | 76 |
| Median TMB (mut/Mb) | 4 | 4 | 3.78 | 3.78 |
| HR+/HER2+ | ||||
| Rearrang | 50 | 27 | 100 | 0 |
| CNV | 0 | 36 | 0 | 50 |
| Mut | 100 | 91 | 100 | 50 |
| Median TMB (mut/Mb) | 1 | 0 | 3.78 | 7.57 |
| HR-/HER2+ | ||||
| Rearrang | 44 | 33 | 0 | 0 |
| CNV | 22 | 33 | 0 | 0 |
| Mut | 89 | 100 | 0 | 0 |
| Median TMB (mut/Mb) | 4 | 1 | 0 | 0 |
| HR+/HER2- | ||||
| Rearrang | 19 | 24 | 15 | 17 |
| CNV | 23 | 21 | 45 | 54 |
| Mut | 86 | 92 | 45 | 64 |
| Median TMB (mut/Mb) | 3 | 3 | 2.52 | 3.78 |
Conclusions
The most commonly altered genes are similar between dnMBC and rMBC. We observed substantial differences in mutational profile assessed by ctDNA vs tissue-based assay.
Clinical trial identification
NCT04932525.
Legal entity responsible for the study
Gustave Roussy.
Funding
Gustave Roussy.
Disclosure
J.R. Dixon Douglas: Financial Interests, Personal, Other, travel and accommodation: MSD; Financial Interests, Personal, Other, accommodation: Novartis, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Gilead Life Sciences. A. Bayle: Financial Interests, Personal, Advisory Board: Sanofi, Roche; Financial Interests, Personal, Other, travel: Pfizer. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Advisory Board, Advisory Board: Menarini, Gilead; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Member of Board of Directors, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Officer, ESMO Clinical Practice Guidelines Chair: ESMO; Non-Financial Interests, Member of Board of Directors, Chair of Clinical Practice Guidelines Committee: ESMO. M.F. Mosele: Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Personal, Full or part-time Employment: PEGASCY. B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca, Seagen, Lilly, Daiichi Sankyo, MSD; Financial Interests, Institutional, Invited Speaker: Gilead, Novartis, AstraZeneca, AstraZeneca, Gilead, Seagen, MSD, Novartis, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, travel support: AstraZeneca, Pierre Fabre, MSD, Daiichi Sankyo; Financial Interests, Personal, Other, Travel support: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Project Lead: Unicancer. F. André: Financial Interests, Personal, Advisory Board: Lilly FRANCE; Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, Roche, Lilly, Pfizer, OWKIN, Novartis, Guardant Health, N-Power Medicine, Servier, Gilead, Boston Pharmaceutics; Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi, Guardant Health, OWKIN. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Invited Speaker: Bayer, AstraZeneca, Roche, MSD, IPSEN, Merck. All other authors have declared no conflicts of interest.