Breast cancer-associated microbiome and its role in treatment efficacy are poorly understood. We aimed to study tumor-associated microbiome composition in TNBC, its dynamics upon NACT, and its correlation with TNBC outcomes.
Diagnostic biopsies and surgery samples from patients with TNBC treated with NACT were selected. A 16S rRNA subunit gene analysis was performed to describe α-diversity with Shannon Index and study taxonomic profiles at genus levels. To control for differences related to the type of sample we also analyzed diagnostic biopsies and surgical samples from patients that had surgery without NACT.
We analyzed 115 TNBC samples from: i) Diagnostic biopsies (n=87) from patients with either subsequent NACT (n=48, mean age 57) or upfront surgery (n=39, mean age 78); ii) Surgery samples (n=28) from patients with prior NACT (n=14, all unpaired; mean age 47) or upfront surgery (n=14, all paired with diagnostic biopsies; mean age 85). α-diversity was significantly lower in post-treatment surgery samples (mean 1.5) compared to pretreatment biopsy samples (mean 1.19, p=0.027), with a significant reduction of Prevotella abudance (p<0.001). Abundance of
Our results suggest that in TNBC, NACT has a significant impact in microbiome composition and some genera are correlated to outcomes. The type of sample (biopsy / surgical) must be taken into account in breast cancer-associated microbiome studies. This work provides the rationale for expanding microbiome analysis in order to find novel putative biomarkers of response to neoadjuvant therapy in early TNBC.
The authors.
European Society for Medical Oncology (ESMO) Translational Research Fellowship to Andri Papakonstantinou, Jose A. Seoane is supported by AEI RYC2019- 026576-I, “LaCaixa” Foundation LCF/PR/PR17/51120011 and Maria Butjosa by a Severo Ochoa fellowship AEI CEX2020-001024-S.”
I. Pimentel: Financial Interests, Personal, Invited Speaker: MSD, Novartis, AstraZeneca; Non-Financial Interests, Member, ASCO member: ASCO; Other, travel and accommodations expenses: Phyzer. E. Zamora: Financial Interests, Personal, Invited Speaker, Review session for medical oncologists: Eisai, Lilly; Other, Registration to ESMO Congress 2022 (virtual): Novartis; Other, Registration to: Eisai. P. Gonzalez Torres: Financial Interests, Personal, Leadership Role: Microomics. N. Carron Rodas: Financial Interests, Personal, Other: Microomics. C. Saura Manich: Financial Interests, Personal, Advisory Board: AX'Consulting, AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann - La Roche Ltd., Gilead, ISSECAM, Lilly, MediTech, Medical Statistics Consulting, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Piere Fabre, PintPharma, Puma, Roche Farma, Sanofi-Aventis, Seagen, Solti, Zymeworks, Pharmalex Spain SLU; Financial Interests, Personal, Expert Testimony: AX's Consulting SARL, Boehringer Ingelheim, Bristol Meyers Squibb, INDITEX, Merck Sharp & Dohme España, Novartis, SACE Medhealth SL, Simon Kucher &Partners SL, Genentech, Innoup, Millenium, Sanofi, Seattle Genetics; Financial Interests, Personal, Other, SC: Byondis B.V., German Breast Group, Glaxo, International Breast Cancer Study Group (IBCSG), Macrogenics, Medsir, Menarini, Merus, Merus, Netherlands Cancer Institute (NKI), Queen Mary (University of London), Seagen, Synthon Biopharpaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., Genentech, GlaxoSmithKline, Immunomedics, Innoup Farma, International Breast Cancer Study Group (IBCSG), Macrogenics, Medica Scientia Innovation Research, Menarini Ricerche, Merus, Novartis, Pfizer, Puma, Roche, Sanofi-Aventis, Seattle Genetics, SOLTI; Financial Interests, Institutional, Invited Speaker: Byondis B.V.; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM), American Society for Clinical Oncology (ASCO), SOLTI group (Academic research group in breast cancer), Geicam (Spanish Breast Cancer Research Group), American Association for Cancer Research (AACR). P.G. Nuciforo: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: MSD Oncology, Bayer; Financial Interests, Personal, Other, Consultant: Targos Molecular Pathology GmbH. M. Oliveira: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo / AstraZeneca, Gilead, Pierre Fabre, Roche, Seagen, iTEOS, Relay Therapeutics; Financial Interests, Personal, Invited Speaker: Gilead, MSD, Novartis, Pfizer, Roche, Seattle Genetics, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer-Ingelheim, GSK, Roche, Seattle Genetics, Zenith Epigenetics, Gilead, Ayala Pharmaceuticals; Financial Interests, Invited Speaker: Roche; Non-Financial Interests, Invited Speaker: SOLTI Breast Cancer Research; Other, Travel Grant: Pierre Fabre, Eisai, Gilead, AstraZeneca. All other authors have declared no conflicts of interest.