Abstract 32P
Background
Women diagnosed under the age 45 and within 5-10 years of a childbirth have increased risk of metastasis. These high-risk cancers, defined as post-partum breast cancer (PPBC), have significantly worse prognosis independent of clinical-pathologic features and demonstrate treatment resistance. We hypothesized that PPBC exhibits high risk molecular profile and sought to define the genomic patterns of PPBC.
Methods
The prospective, observational FLEX Study (NCT03053193) includes stage I-III early BC patients who received MammaPrint®(MP) and/or BluePrint®(BP) testing and consented to full transcriptome and clinical data collection. We identified 377 HR positive and HER2-negative patients, age ≤50, grouped as PP 0-5 years [n=33]; PP 6-10 years [n=51]. Two control groups PP >10 years [n=175] and nulliparous [n=118] were used for comparison. Median age, clinical characteristics, metabolic factors, and genomic test results (MP and BP) were compared between PP groups and nulliparous. Limma R package was used for differential gene expression analysis in age-matched cohorts. Pathway analysis was conducted using Metascape.
Results
PPBC 0-5 had a significantly higher frequency of MP High 2 and lower frequency of MP Low Risk compared to nulliparous women (p=0.02). PP 0-5 had higher frequency of Luminal B and Basal compared to PP >10 years (p=0.01). In gene expression analysis, PP 0-5 cohort had 25 genes with 2-fold higher expression compared to nulliparous including genes like MUCL1, CLEC3A, CXCL9. Pathway analysis demonstrated increased adaptive immune-mediated and humoral- response pathways in PP 0-5 years.
Conclusions
In this study, PPBC 0-5 years of childbirth demonstrates significantly higher risk of recurrence (MP High 2) and increased immune gene expression, other unique genes/pathways related to PPBC biology compared to BC occurring >10 years after childbirth or in nulliparous women. These findings are consistent with the poor clinical outcomes previously reported for PPBC. Increased frequency of MP High 2 tumors and immune biology indicate that PPBC might benefit from adding immunotherapy, to be explored in future trials.
Clinical trial identification
NCT03053193.
Legal entity responsible for the study
Agendia Inc.
Funding
Agendia Inc.
Disclosure
V.F. Borges: Financial Interests, Personal and Institutional, Principal Investigator, Consultant and research support to my institution: Seagen; Financial Interests, Personal and Institutional, Advisory Role, Research support to my instution and KOL/Consultant: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Role, Research support to my instution and KOL/consultant role: Gilead; Financial Interests, Institutional, Principal Investigator, Research funding to my institution, presenting author for one study: Olema. E. Shagisultanova: Financial Interests, Personal, Advisory Board, Advisory Board on CDK4/6 inhibitors, October 2019: Novartis; Financial Interests, Institutional, Funding, Funding for investigator initiated clinical trial: Novartis, Seagen, Pfizer; Financial Interests, Institutional, Invited Speaker, Site PI on clinical trial: Lilly. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie, Agendia, Amgen, Aptitude Health, AstraZeneca, Bristol Myers Squibb, Celgene, Eisai, G1 Therapeutics, Genentech, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Novartis, Ondonate, Pfizer, Puma, Prime Oncology, Roche, Seattle Genetics, Syndax, Carrick Therapeutics, Daiichi Sankyo, Gilead Sciences, Ontada, Pierre Fabre Pharmaceuticals, Samsung Bioepis, Sanofi. A.M. Brufsky: Financial Interests, Personal, Advisory Role: Pfizer, Genentech/Roche, Agendia, Novartis, Lilly, Puma Biotechnology, Merck, Myriad Pharmaceuticals, Eisai, Seagen, Daiichi Sankyo/Lilly, OncLive, Michael J. Hennessy Associates, Gilead Sciences, General Electric; Financial Interests, Institutional, Research Grant: Roche/Genentech, AstraZeneca/Daiichi Sankyo, Merck, Novartis, Gilead Sciences, Lilly, Puma Biotechnology. R. Mahtani: Financial Interests, Personal, Other, Consultant: Agendia, Amgen, Biotheranostics, Daiichi Sankyo, Genentech, Immunomedics, Lilly, Merck, Novartis, Pfizer, Puma, Sanofi, Seagen; Financial Interests, Personal, Advisory Board, Consultant and served on advisory boards: AstraZeneca; Financial Interests, Personal, Advisory Board, Consultant: Eisai, Stemline. K. Hoskins: Non-Financial Interests, Institutional, Principal Investigator: Agendia; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, Novartis, AbbVie, Pfizer, Genentech. N. D'abreo, S. Uygun, Samraj: Financial Interests, Personal, Full or part-time Employment: Agendia Inc. W. Audeh: Financial Interests, Personal, Full or part-time Employment: Agendia Inc.; Financial Interests, Personal, Leadership Role: Agendia Inc.; Financial Interests, Personal, Research Grant: Agendia Inc.; Financial Interests, Personal, Advisory Role: Celanese, Private Health, Quantum Health. All other authors have declared no conflicts of interest.